PearlMatrix™ Bone Graft

P240001 · Cerapedics, Inc. · NOX · Jun 18, 2025 · Orthopedic

Device Facts

• Record ID: P240001
• Device Name: PearlMatrix™ Bone Graft
• Applicant: Cerapedics, Inc.
• Product Code: NOX · Orthopedic
• Decision Date: Jun 18, 2025
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Indications for Use

PearlMatrix™ Bone Graft is indicated for intervertebral body fusion of the spine in skeletally mature patients. PearlMatrix™ Bone Graft is intended to be used in conjunction with a PEEK TLIF Fusion Device and supplemental internal spinal fixation systems cleared by the FDA for use in the lumbosacral spine. The system is to be used in patients who have had at least six months of non-operative treatment. PearlMatrix™ Bone Graft is intended for use at one level in the lumbar spine (L2-S1) for the treatment of degenerative disc disease (DDD) with up to Grade I spondylolisthesis. DDD is defined as back and/or radicular pain of discogenic origin with degeneration of the disc confirmed by history, physical exam, and radiographic studies.

Device Story

PearlMatrix™ Bone Graft is a composite bone graft substitute for lumbar interbody fusion. It consists of porcine anorganic bone mineral (pABM) particles coated with a synthetic 15-amino acid peptide (P-15) that mimics human Type I collagen, embedded in a bovine collagen matrix carrier. The device is supplied as a dry material, hydrated by the surgeon with saline or Ringer’s lactate, and kneaded into a moldable putty. It is implanted into the interbody space during a TLIF procedure alongside a PEEK cage and internal fixation. The pABM/P-15 particles provide a scaffold for new bone growth, while the collagen carrier aids in placement and is resorbed via enzymatic digestion. The device facilitates cell attachment and bone remodeling. It is intended for use by spine surgeons in a hospital setting. The graft is designed to promote fusion in patients with degenerative disc disease, potentially reducing the need for autograft harvesting and associated donor site morbidity.

Clinical Evidence

Pivotal multi-center, single-blinded, randomized controlled trial (ASPIRE, IDE G170300) comparing PearlMatrix™ Bone Graft (n=143) to local autograft (n=150) in single-level TLIF. Primary endpoint: Month 24 Composite Clinical Success (CCS) (no secondary surgery, radiographic fusion, ODI improvement ≥15, no neurological deficit, no serious device-related AE). PearlMatrix™ achieved 55.4% CCS vs 36.4% control (p=0.0000002 non-inferiority; p=0.0012 superiority). Fusion rates at 24 months were 83.7% (PearlMatrix) vs 57.3% (control). Safety profile showed similar rates of AEs and SAEs, though procedure-related SAEs were higher in the PearlMatrix arm.

Technological Characteristics

Composite bone graft: 80% (w/w) porcine anorganic bone mineral (pABM) particles coated with synthetic P-15 peptide, 20% (w/w) bovine collagen carrier. Form factor: moldable putty after hydration. Sterilization: terminal gamma radiation (SAL 10⁻⁶). Shelf life: 3 years. No electronic components or software.

Indications for Use

Indicated for intervertebral body fusion of the spine in skeletally mature patients with degenerative disc disease (DDD) and up to Grade I spondylolisthesis at one lumbar level (L2-S1) after 6 months of failed non-operative treatment. Contraindicated in patients with active infection, sensitivity to graft components, lack of load-bearing support, or operative sites subject to excessive stress.

Regulatory Classification

Identification

The device acts as a bone void filler and consists of a filling material and a synthetic peptide. It is intended to fill traumatic or surgically-created defects that are not intrinsic to the bony structure of the extremities, spine or pelvis. It will be packed or placed into the defect and will resorb over time to be replaced by bone.

Reference Devices

• i-FACTOR Bone Graft

Submission Summary (Full Text)

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FDA U.S. FOOD & DRUG ADMINISTRATION
CENTER FOR OFFICIAL & RAPID LINGUIS, DOLLAR

# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

## I. GENERAL INFORMATION

Device Generic Name: Peptide Enhanced Bone Graft Substitute

Device Trade Name: PearlMatrix™ P-15 Peptide Enhanced Bone Graft, or PearlMatrix™ Bone Graft

Device Product Code: NOX

Applicant’s Name and Address: Cerapedics, Inc.
11025 N. Dover Street, Suite 1600
Westminster, CO 80021

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P240001

Date of FDA Notice of Approval: June 18, 2025

Breakthrough Device: Granted breakthrough device status on April 14, 2021, because the combination product represents a novel technology for intervertebral body fusion of the lumbar spine when used in conjunction with a transforaminal lumbar interbody fusion (TLIF) device and internal spinal fixation.

## II. INDICATIONS FOR USE

PearlMatrix™ Bone Graft is indicated for intervertebral body fusion of the spine in skeletally mature patients. PearlMatrix™ Bone Graft is intended to be used in conjunction with a PEEK TLIF Fusion Device and supplemental internal spinal fixation systems cleared by the FDA for use in the lumbosacral spine. The system is to be used in patients who have had at least six months of non-operative treatment. PearlMatrix™ Bone Graft is intended for use at one level in the lumbar spine (L2-S1) for the treatment of degenerative disc disease (DDD) with up to Grade I spondylolisthesis. DDD is defined as back and/or radicular pain of discogenic origin with degeneration of the disc confirmed by history, physical exam, and radiographic studies.

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PMA P240001: FDA Summary of Safety and Effectiveness Data

# III. CONTRAINDICATIONS

PearlMatrix™ Bone Graft should not be used in situations where there is:

- An absence of load bearing structural support at the graft site
- Sensitivity to components of PearlMatrix™ Bone Graft
- Active infection at the operative site
- Operative site subject to excessive impact or stress

# IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the PearlMatrix™ Bone Graft labeling.

# V. DEVICE DESCRIPTION

PearlMatrix™ Bone Graft is a composite bone graft material consisting of a synthetic peptide (P-15) found naturally occurring in human Type I collagen, adsorbed onto calcium phosphate particles, which are incorporated into a bovine collagen matrix as an inert carrier. The calcium phosphate particles, also known as porcine anorganic bone mineral (pABM), are derived from porcine bone and provide a scaffolding and source of calcium for new bone growth. The synthetic collagen fragment (P-15) is a short chain 15 amino acid peptide that mimics a cell binding domain of human Type I collagen, thus providing a more favorable environment that facilitates cell attachment on the pABM scaffold. The pABM/P-15 particles are the functional component of the bone graft, whereas the bovine collagen simply acts as an inert carrier, aiding in the placement and containment of the particles at the graft site. After implantation, the collagen is resorbed via naturally occurring cellular enzyme digestion and the pABM/P-15 particles are concomitantly enveloped and stabilized by new tissues and are eventually remodeled into native bone via cell mediated resorption.

The composition of PearlMatrix™ Bone Graft is shown in the following table.

TABLE 1 – PearlMatrix™ Bone Graft Composition

| Components | Quantity per 1cc | Proportion (w/w) |
| --- | --- | --- |
| pABM/P-15 particles | 0.61g | 80% |
| Collagen | 0.15g | 20% |

PearlMatrix™ Bone Graft is provided in four different volumes (1.0cc, 2.5cc, 5.0cc, and 10.0 cc) and is prepared by the surgeon by hydrating it with sterile solution (i.e., saline or Ringer’s lactate) and kneading it to produce a putty form that can be molded into the desired shape.

A picture of PearlMatrix™ Bone Graft pre-hydration is provided in FIGURE 1. A picture of PearlMatrix™ Bone Graft after hydration and kneading is provided in FIGURE 2.

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FIGURE 1 - PearlMatrix™ Bone Graft before hydration

FIGURE 2 - PearlMatrix™ Bone Graft after hydration and kneading to form a putty

## VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several non-surgical and surgical alternatives for the treatment of lumbar DDD. Non-surgical alternative treatments may include physical therapy and/or pain relief medications. Surgical alternatives may include lumbar fusion (with or without the use of metallic implants) with autograft or allograft bone, or artificial lumbar disc replacement surgery. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

## VII. MARKETING HISTORY

PearlMatrix™ Bone Graft has been marketed in Canada in April 2020 under the name i-FACTOR®+ Matrix Bone Graft. The device has not been withdrawn from distribution/marketing for safety or effectiveness reasons.

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# VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (e.g., complications) associated with the use of the product. The adverse effects are sub-divided into three categories: (1) those commonly associated with any surgical procedure; (2) those associated with lumbar spinal surgery procedures using a transforaminal approach; and (3) those associated with the use of a bone graft, including those pertaining to PearlMatrix™ Bone Graft. In addition to the risks listed below, there is also the risk that the procedure may not be effective and may not relieve or may cause worsening of pre-operative symptoms. Additional surgery may be required to correct some of the potential adverse effects.

Potential adverse effects associated with any surgical procedure include:

- Anesthesia complications, including allergic reaction, anaphylaxis, or other reactions to anesthesia
- Reaction to transfused blood
- Anemia
- Blood loss/hemorrhage
- Heart or vascular complications, including:
- Excessive bleeding or injury to blood vessels
- Edema
- Hematoma or seroma
- Hypotension or hypertension
- Ischemia
- Cardiac event
- Myocardial infarction
- Embolism, including pulmonary embolism
- Thrombosis
- Thromboembolism
- Thrombophlebitis
- Phlebitis
- Stroke
- Hemorrhage or vascular damage resulting in catastrophic or potentially fatal bleeding
- Septicemia
- Cerebral vascular accident (stroke)
- Pulmonary complications, including atelectasis, pneumothorax, pneumonia, pulmonary edema, and respiratory distress
- Blindness secondary to pressure on the eye during surgery
- False aneurysm
- Headache
- Infection (wound, local, and/or systemic) abscess, or cellulitis
- Soft tissue damage or fluid collections, including edema, hematoma, or seroma, which may require drainage, aspiration, debridement, or other intervention
- Surgical wound dehiscence, necrosis, or scarring of tissue around the wound

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- Post-surgical pain, bruising, tenderness or discomfort at the surgical site or incision and/or skin or muscle sensitivity over the incision which may result in skin breakdown, pain, and/or irritation
- Impairment of the gastrointestinal system including ileus or bowel obstruction, nausea, or vomiting
- Impairment of the genitourinary system including incontinence, bladder dysfunction, urinary tract infection, or reproductive system complications
- Neurological complications including nerve damage, paralysis, seizures or convulsions, changes to mental status, or reflex sympathetic dystrophy
- Psychological illness
- Injury to muscles, or organs
- Insomnia
- Narcotic addiction
- Numbness
- Complications of pregnancy including miscarriage or congenital defects
- Inability to resume activities of daily living
- Death

Potential adverse effects associated with an instrumented single-level TLIF surgery with any type of bone graft include:

- Risks to neurological structures:
- Dural tear dural leak and/or dural injury with or without CSF leakage
- Arachnoiditis
- Compressive neuropathy
- Neurologic deterioration - injury to nerves or nerve roots associated with the spinal cord (resulting in pain, weakness, paralysis (partial or complete), paresthesia, altered reflexes, numbness, tingling, or other changes in sensation)
- Coordination abnormalities
- Gait disturbance
- Headache
- Otitis media
- Tremors
- Cerebrospinal fluid leakage
- Cerebrospinal fistula
- Reflex Sympathetic Dystrophy (RSD)
- Cauda equina syndrome
- Damage to nerves, blood vessels, and nearby tissues
- Impaired muscle or nerve function
- Epidural bleeding, hematoma, or fibrosis
- Bone necrosis
- Degenerative changes in adjacent segment
- Surgery at incorrect level
- Osteolysis

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- Loss of bowel or bladder function
- Incontinence (loss of bowel or bladder control)
- Fracture of the vertebrae, spinous process, or other damage to bony structures during or after surgery
- Postoperative muscle and tissue pain
- Development of disc degeneration at adjacent levels
- Inflammatory conditions
- Loss of disc height
- Disc herniation
- Undesirable change in lordosis
- Scarring or soft tissue damage
- Spinal instability
- Spondylolisthesis acquisita (vertebral slippage)
- Retrolisthesis
- Spinal stenosis (narrowing of the spinal canal)
- Spondylosis
- Facet joint deterioration
- Infection of the bone, or surrounding soft tissue
- Musculoskeletal spasms (back or leg)
- Perineural fibrosis
- Surgery may not reduce the preoperative pain
- Pain and discomfort associated with the presence of implants
- Pain and discomfort associated with the surgical procedure (e.g., cutting of muscles, ligaments, and tissue) and healing
- The spine may undergo adverse changes or deterioration including loss of proper spinal curvature, correction, height, and/or reduction, or malalignment, and another surgery may be required
- Adverse bone/implant interface reaction
- Extrusion or migration of the bone graft, resulting in pain, neural impingement, physical impairment, or loss of function, any of which may require revision surgery
- Abnormal bone formation in an unintended location
- Excessive or incomplete bone formation

Potential adverse effects associated with the use of PearlMatrix™ Bone Graft include:

- Allergic/immune response to components of the PearlMatrix™ Bone Graft

For the specific adverse events that occurred in the clinical study please see Section X(D).

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PMA P240001: FDA Summary of Safety and Effectiveness Data

# IX. SUMMARY OF NON-CLINICAL STUDIES

## A. Laboratory Studies

### Biocompatibility

The components of PearlMatrix™ Bone Graft (ABM, P-15 peptide, and bovine collagen) have well established safety and biocompatibility profiles when used separately or in combination with other materials. Previous PMA approvals on ABM/P-15 based products were supported by appropriate ISO 10993 biocompatibility testing.

Standard biocompatibility testing was conducted on PearlMatrix™ Bone Graft in accordance with international standard ISO 10993-1, Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing. The following tests were performed:

- Cytotoxicity
- Sensitization
- Irritation
- Acute Systemic Toxicity
- Pyrogenicity
- Genotoxicity (In Vitro Chromosomal Aberration Study in Mammalian Cells)
- Implantation

The ISO 10993 testing determined PearlMatrix™ Bone Graft to be nontoxic, nonirritating, non-sensitizing, and non-mutagenic.

## B. Animal Studies

TABLE 2 - Nonclinical Tests Performed on PearlMatrix™ Bone Graft

| Test | Method | Results |
| --- | --- | --- |
| Ovine Critical Size Defect | Drill hole model to demonstrate the kinetics of new bone formation initiated by PearlMatrix™ Bone Graft | PearlMatrix™ Bone Graft yielded more bone formation than i-FACTOR Bone Graft and ABM/Collagen |
| Rabbit Ectopic Bone Formation | Implantation of PearlMatrix™ Bone Graft in a Rabbit muscle pouch | PearlMatrix™ Bone Graft did not induce ectopic bone formation |

Both the nonclinical laboratory tests and in-vivo tests on PearlMatrix™ Bone Graft have demonstrated that PearlMatrix™ Bone Graft is safe for use in lumbar procedures. PearlMatrix™ Bone Graft has been shown to be biocompatible. Animal models have demonstrated that PearlMatrix™ Bone Graft is equivalent to or better than previously approved i-FACTOR relative to bone formation. Both animal and

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human studies have demonstrated that P-15 peptide-based bone grafts do not elicit a measurable adverse immune response.

## C. Additional Studies

### Sterilization, Shipping, and Shelf Life

PearlMatrix™ Bone Graft is terminally sterilized in the final package configuration using gamma radiation. Sterilization validation was performed on the product in its packaging according to AAMI/ISO 11137-Part 1: 2006 and Part 2: 2013 – Sterilization of Health Care Products – Radiation. The sterilization validation confirmed the dose range capability of providing a sterility assurance level (SAL) of 10⁻⁶.

PearlMatrix™ Bone Graft was tested for the rigors of shipping and handling per ASTM D 4169-16: Performance Testing of Shipping Containers and Systems.

PearlMatrix™ Bone Graft is currently specified to have a shelf life of three (3) years from the date of sterilization. Results of stability study showed that accelerated and real-time aged product stored at ambient room temperature and humidity conditions remains stable and sterile over the shelf life of three (3) years.

## X. SUMMARY OF PRIMARY CLINICAL STUDY

Cerapedics performed a clinical study to establish a reasonable assurance of safety and effectiveness of the PearlMatrix™ Bone Graft for treatment of degenerative disc disease (DDD) with up to Grade I spondylolisthesis at one level in the lumbar spine (L2-S1) when used in conjunction with a polyetheretherketone (PEEK) cage device cleared for TLIF and supplemental internal spinal fixation systems in patients who have had at least six months of non-operative treatment. The clinical study was conducted in the US under IDE G170300. Data from this clinical study were reviewed for the PMA approval decision. A summary of the clinical study is presented below.

### A. Study Design

Subjects (patients) were treated between July 26, 2018, and February 3, 2022. The database for this PMA reflected data collected through June 14, 2024, and included 293 subjects. There were 33 investigational sites.

The study titled "An Assessment of P-15L Bone Graft in Transforaminal Lumbar Interbody Fusion with Instrumentation" (ASPIRE) was a multi-center single (subject)-blinded randomized controlled trial clinical study. The objective of the study was to evaluate whether PearlMatrix™ Bone Graft was non-inferior to local autologous bone optionally mixed with allograph when applied in instrumented TLIF with use of an interbody spacer in subjects with lumbar degenerative disc disease. In addition to the general overall objective, planned sub-group analyses were performed on the higher risk subject population (nicotine use, obesity, type 2 diabetes), as previous studies have suggested negative effects of smoking, obesity and diabetes on

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fusion and bone healing, increased peri/postoperative complications, and lower patient-reported outcome scores.

Subjects were randomized and treated in a 1:1 ratio to either the Investigational arm (TLIF with the PearlMatrix™ Bone Graft) or the active Control arm. The Control arm consisted of subjects undergoing a TLIF procedure with local autograft bone optionally mixed with allograft. A total of 141 subjects were treated in the PearlMatrix™ Bone Graft arm of the study and a total of 149 subjects were treated in the Control arm of the study.

In both arms, bone grafting was in the interbody space alone, without decortication nor bone grafting of the posterolateral gutters; facet decortication/resection was allowed for surgical exposure or facet arthrosis as needed, also without bone grafting.

The primary outcome measure for the non-inferiority hypothesis was composite clinical success. Composite Clinical Success (CCS) was defined as a subject level endpoint. To achieve CCS, a subject must have all 5 variables in the composite at month 24: no index level secondary surgical intervention; radiographic fusion by computed tomography (CT); at least a 15-point improvement in Oswestry Disability Index (ODI) from baseline; no new or worsening persistent neurological deficit relative to baseline; and no serious device-related adverse events.

1. Clinical Inclusion and Exclusion Criteria

Enrollment in the ASPIRE study was limited to patients who met the following inclusion criteria:

- Skeletally mature adults between 22 and 80 years old (inclusive)
- Back pain with radicular symptoms as evidenced by leg pain, confirmed by history and physical exam
- Radiographically determined discogenic origin of the pain demonstrating at least one of the following characteristics: Degenerated/dark disc on MRI, instability (angulation $\geq 5^{\circ}$ and/or translation $\geq 3\mathrm{mm}$ on flexion/extension radiographs), osteophyte formation, ligamentous thickening, decreased disc height compared to adjacent levels on radiographic film, CT, or MRI, and disc herniation on CT or MRI
- Oswestry Low Back Pain Disability Questionnaire score of $\geq 35$
- Involved disc(s) between L2 and S1
- Planned lumbar fusion at a single level only
- Failed to gain adequate relief from at least 6 months of adequate non-operative treatment
- Able and willing to give consent to participate in study
- Willing and able to participate in the study follow-up according to the protocol
- Willing and able to comply with postoperative management program

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Patients were not permitted to enroll in the ASPIRE study if they met any of the following exclusion criteria:

- Systemic infection such as AIDS, HIV, and active hepatitis
- Autoimmune disease that affects bone formation
- Significant metabolic disease that, in the surgeon’s opinion, might compromise bone growth such as osteoporosis, osteopenia, or osteomalacia
- Taking medication for the prevention of osteoporosis or other medications that may interfere with fusion (e.g., steroids, or has received drugs that interfere with bone metabolism within 2 weeks of surgery)
- Circulatory, cardiac, or pulmonary problems that could cause excessive surgical risk
- Active malignancy
- Nondiscogenic source of symptoms (e.g., tumor, etc.)
- Multiple level symptomatic degenerative disc disease where more than one level requires fusion
- Previous spinal instrumentation or a previous interbody fusion procedure at the involved level
- Isthmic Spondylolisthesis
- Spondylolisthesis ≥ grade 2 if present
- Active local or systemic infection
- Known allergy to components within PearlMatrix™ Bone Graft including bovine collagen; PEEK, or materials in supplemental fixation systems
- Pregnant or planning to become pregnant in the next 2 years
- More than one level to be fused (note: multi-level decompression is acceptable)
- Has a history of substance abuse (e.g., recreational drugs, alcohol) within the past 2 years
- Is a prisoner
- Is currently involved in a study of another investigational product for similar purpose
- Has a disease process that would preclude accurate evaluation (e.g. neuromuscular disease, significant psychiatric disease)
- Has active or recent (within the past 2 years) Worker’s compensation litigation
- Any condition that would interfere with the subject’s ability to comply with the study-related requirements

2. Follow-up Schedule

All patients were scheduled to return for follow-up examinations for up to 72 months postoperatively. This included time during initial hospitalization (baseline), and planned follow-up visits, which consisted of 6 weeks ± 10 days, 3 months ± 14 days, 6 months ± 30 days, 12 months ± 60 days, 24 months ± 60 days, 36 months ± 120 days, 48 months ± 120 days, 60 months ± 120 days, and

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72 months ± 120 days. The key timepoints and assessment are shown below in TABLE 3.

TABLE 3 - Study Schedule

| Procedure | Visit 1 (-60 to -1 d) | Visit 2 (day 0) | Visit 3 (+/- 10d) | Visit 4 (+/- 14d) | Visit 5 (+/- 30d) | Visit 6 (+/- 60d) | Visit 7 (+/- 60d) | Visit 8 (+/- 120d) | Visit 9 (+/- 120d) | Visit 10 (+/- 120d) | Visit 11 (+/- 120d) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Baseline | Surgery | 6w | 3m | 6m | 12m | 24m | 36m | 48m | 60m | 72m |
| Informed Consent | X | | | | | | | | | | |
| Medical History | X | | | | | | | | | | |
| Demographics | X | | | | | | | | | | |
| Subject Eligibility Verification | X | | | | | | | | | | |
| Randomization | | X | | | | | | | | | |
| Treatment | | X | | | | | | | | | |
| Pregnancy test | Xc | | | | | | | | | | |
| VAS | X | | X | X | X | X | X | X | X | X | X |
| Clinical exam | X | | X | X | X | X | X | X | X | X | X |
| ODI | X | | | X | X | X | X | X | X | X | X |
| SF-12 | X | | | | X | X | X | X | X | X | X |
| Blood Draw | Xf | | X | X | X | X | Xa | Xa | Xa | Xa | Xa |
| Radiographs (Flexion/ Extension) | Xd | | | | | | X | | | | |
| Radiographs (AP/Lateral) | Xd | Xe | Xe | Xe | Xe | Xe | X | X | X | X | X |
| Prior Medications | X | | | | | | | | | | |
| CT | | | | | X | Xb | Xb | | | | |
| Concomitant Medications | | X | X | X | X | X | X | X | X | X | X |
| Adverse Events | | X | X | X | X | X | X | X | X | X | X |

a - Blood draw is required only if baseline sera results are not achieved.
b - To reduce unnecessary radiation exposure, visits 6 (month 12) and 7 (month 24) CT will not be required if independent review is deemed fused at the 6- or 12-month assessment.
c - Pregnancy test can be collected on day of surgery based on institution's standard policies. Both urine and serum pregnancy testing are acceptable.
d - Radiographs collected prior to the 60-day window in the baseline visit that were used to diagnose the need for surgery will be accepted to reduce additional radiation exposure
e - Obtain any standard of care x-rays of the lumbar region.
f - Collection of the blood draw may be completed on the day of surgery prior to treatment.

Adverse events and complications were recorded at all visits.

The key timepoints are shown below in the tables summarizing safety and effectiveness.

# 3. Clinical Endpoints

The primary endpoint was the Month 24 Composite Clinical Success (CCS). All the following had to be achieved for a patient to be classified as achieving primary Month 24 CCS:

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- No index level secondary surgical intervention to Study Day 730 (i.e. 24 months);
- Achievement of fusion by Month 24 visit (Fusion is defined as evidence of bridging trabecular bone between the vertebral bodies by CT scan on axial, sagittal or coronal reconstructions;
- At least 15-point improvement in ODI from baseline to Month 24 visit on a 100-point scale;
- No new or worsening, persistent neurological deficit comparing Month 24 to baseline (i.e., maintenance or improvement of the baseline motor and sensory scores on 5-point scales), and
- No serious device-related adverse event to Study Day 730 (i.e. 24 months).

Secondary endpoints CCS superiority and time-to-fusion superiority were prespecified endpoints with a multiplicity-controlled hypothesis. Other secondary endpoints evaluated during the study included the following: back pain and leg pain, as measured by a 10-point Visual Analog Scale ("VAS"); quality of life, assessed using the SF12® questionnaire.

## B. Accountability of PMA Cohort

At the time of database lock, of 293 subjects enrolled in the PMA study (mITT set), 121 subjects in the PearlMatrix™ Bone Graft arm and 129 subjects in the Control arm were evaluable for Month 24 CCS.

The definitions of the analysis populations are provided below.

- Modified Intent-to-Treat (mITT): All randomized patients with a surgical or anesthesia start time were specified to be included in the intent-to-treat (ITT) analysis set according to the device group to which they were randomized. A modified ITT (mITT) population included all subjects who were randomized and had surgical procedures initiated. There were three (3) subjects who were randomized and for whom surgery was started, but they were removed from the study at surgery because they did not receive any study treatment. In addition, there was one subject who was randomized to PearlMatrix™ Bone Graft but received the Control treatment. This subject is still accounted for in the PearlMatrix™ Bone Graft population in the mITT accountability. The mITT set is the primary analysis set for the primary endpoint.
- As Treated (AT): The As Treated (AT) analysis set was defined similarly to the ITT analysis set except that patients were analyzed according to the device actually received. Primary safety analyses were conducted in the AT analysis set. All randomized subjects were treated according to the assigned treatment with the exception of one subject at Site 20 in which the subject was randomized to the investigational arm but was treated as a control subject. This subject was included in the Control arm in the AT population.

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- Per-Protocol (PP): The PP analysis set excluded from the ITT analysis set patients that did not receive a device, with clinically significant violations of inclusion or exclusion criteria or post randomization protocol violations that may reasonably be predicted to impact on effectiveness endpoints. Subjects were analyzed according to the actual treatment received. The PP set is reported as a sensitivity analysis in addition to the mITT set when its reporting is useful.

Subject accountability for the mITT population is shown in FIGURE 3 and is based on 293 subjects. Clinical visit follow-up of subjects at 24 months in the mITT population was 86.7% and 86.9% for the PearlMatrix™ Bone Graft and Control arms, respectively. Based on theoretical due status and subtracting only deaths among theoretical due, 85.8% in the PearlMatrix™ Bone Graft arm and 86.6% in the Control arm were evaluable for Month 24 CCS.

Subject accountability for the As Treated (AT) population is provided in FIGURE 3 and is based on 290 subjects. The AT population excluded the three (3) subjects who were randomized and received a non-study treatment. In addition, the subject who was randomized to the PearlMatrix™ Bone Graft arm but received a Control treatment is accounted for in the Control arm.

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FIGURE 3 - Subject (Patient) Accountability

The randomization sequence was generated using block randomization; two block sizes (2 and 4 subjects per block) were included in the algorithm and were randomly shuffled. This scheme made breaking the blind by working out the block pattern extremely difficult and reasonably protects against biased allocation of subjects. Randomization was performed in a 1:1 ratio between the Investigational and Control arms within site and risk group (higher and normal risk). The risk group stratification was introduced to promote between group balance in the numbers of subjects in the

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higher and normal risk groups and to optimize sub-group analysis of the higher risk subject population (nicotine use, obesity, and Type 2 diabetes). In total, 299 patients were randomized. Among these 299 subjects, 141 subjects received the Investigational (PearlMatrix™ Bone Graft) treatment, and 149 subjects received the Control treatment (local bone mixed with allograft chip if needed). These subjects comprised the As Treated (AT) analysis set. One subject was randomized to PearlMatrix™ Bone Graft but received Control. This subject was analyzed as treated in the AT analysis set. There were 3 randomized subjects that commenced their index surgery, but there was no attempt at delivering a study treatment. These subjects were included in the mITT analysis set as CCS failures. In the mITT analysis set, the subject randomized to the PearlMatrix™ Bone Graft arm but who received control was analyzed as randomized. The six (6) randomized subjects that withdrew prior to surgery were not included in either the AT or mITT analyses sets. The mITT study population was 62.2% (N=89) high risk in the PearlMatrix™ Bone Graft arm and 63.3% (N=95) in Control arm).

## C. Study Population Demographics and Baseline Parameters

The demographics of the study population are typical for a degenerative disc disease interbody fusion study performed in the US.

TABLE 4 provides the study population demographics. The average age of all subjects treated in the PearlMatrix™ Bone Graft arm was 58.7 years (standard deviation (SD) 12.2) and the average age of the Control arm was 59.6 years (SD 10.9). Overall BMI was similar for both groups, 31.2 with a SD of 6.4 for the PearlMatrix™ Bone Graft arm and 31.3 with a SD of 5.9 for the Control arm.

For all males, the average age of subjects treated in the PearlMatrix™ Bone Graft arm was 58.6 years (SD 11.9) and the average age of the Control arm was 59.2 years (SD 10.8). Overall BMI was 31.1 (SD 5.7) for those in the PearlMatrix™ Bone Graft arm and the overall BMI for those in the Control arm was 30.9 (SD 5.7).

For all females, the average age of subjects treated in the PearlMatrix™ Bone Graft arm was 58.8 years (SD 12.5) and the average age of the Control arm was 60.0 years (SD 11.0). Overall BMI was 31.3 (SD 7.0) for those in the PearlMatrix™ Bone Graft arm and 31.6 (SD 6.0) for those in the Control arm.

Regarding functional status, the ODI was a contributor to the primary composite endpoint. The baseline ODI for the PearlMatrix™ Bone Graft arm was 54.7 (SD 13.5) while the Control arm baseline ODI was 53.7 (SD 14.5). Per the protocol, the baseline minimum ODI for inclusion in the study was 35. There were two documented protocol deviations in the Control arm for ODI scores below the minimum (28 and 32).

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TABLE 4 - Summary of Baseline and Demographic Continuous Variables - mITT Population

| | PearlMatrix™ Bone Graft | | | | | | Autologous bone | | | | | | PearlMatrix™ Bone Graft - Autologous Bone† | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Demographics - All | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | Diff | LB | UB |
| Age at surgery (yrs) | 143 | 58.7 | 12.2 | 59.0 | 26.0 | 80.0 | 150 | 59.6 | 10.9 | 61.0 | 30.0 | 79.0 | -0.9 | -3.6 | 1.8 |
| Height (in) | 143 | 67.0 | 4.3 | 67.0 | 58.0 | 79.0 | 147 | 67.0 | 3.9 | 67.0 | 59.0 | 76.0 | 0.0 | -1.0 | 0.9 |
| Weight (lb) | 143 | 200.1 | 48.7 | 195.0 | 95.3 | 360.0 | 147 | 200.1 | 42.1 | 194.0 | 121.0 | 327.0 | 0.0 | -10.5 | 10.5 |
| BMI (k/m2) | 143 | 31.2 | 6.4 | 31.2 | 16.4 | 49.7 | 147 | 31.3 | 5.9 | 30.4 | 21.6 | 47.8 | -0.1 | -1.5 | 1.3 |
| Demographics - Male | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | Diff | LB | UB |
| Age at surgery (yrs) | 66 | 58.6 | 11.9 | 59.0 | 32.0 | 78.0 | 75 | 59.2 | 10.8 | 60.0 | 36.0 | 79.0 | -0.7 | -4.5 | 3.1 |
| Height (in) | 66 | 70.7 | 2.8 | 70.4 | 65.0 | 79.0 | 73 | 69.8 | 3.2 | 70.0 | 60.0 | 76.0 | 0.9 | -0.1 | 2.0 |
| Weight (lb) | 66 | 221.9 | 47.0 | 215.0 | 150.0 | 360.0 | 73 | 213.9 | 40.2 | 210.0 | 137.0 | 327.0 | 8.0 | -6.6 | 22.7 |
| BMI (k/m2) | 66 | 31.1 | 5.7 | 30.6 | 20.8 | 49.7 | 73 | 30.9 | 5.7 | 29.4 | 22.1 | 47.8 | 0.2 | -1.7 | 2.1 |
| Demographic - Female | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | Diff | LB | UB |
| Age at surgery (yrs) | 77 | 58.8 | 12.5 | 59.0 | 26.0 | 80.0 | 75 | 60.0 | 11.0 | 62.0 | 30.0 | 79.0 | -1.1 | -4.9 | 2.6 |
| Height (in) | 77 | 63.8 | 2.6 | 64.0 | 58.0 | 70.0 | 74 | 64.3 | 2.4 | 65.0 | 59.0 | 69.0 | -0.5 | -1.3 | 0.3 |
| Weight (lb) | 77 | 181.5 | 42.1 | 187.0 | 95.3 | 278.0 | 74 | 186.5 | 39.7 | 183.2 | 121.0 | 302.0 | -5.1 | -18.2 | 8.1 |
| BMI (k/m2) | 77 | 31.3 | 7.0 | 31.3 | 16.4 | 47.4 | 74 | 31.6 | 6.0 | 30.6 | 21.6 | 46.8 | -0.3 | -2.4 | 1.8 |
| Baseline Functional Status | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | Diff | LB | UB |
| Oswestry Disability Index (ODI) | 143 | 54.7 | 13.5 | 52.0 | 36.0 | 93.0 | 150 | 53.7 | 14.5 | 52.0 | 28.0 | 100.0 | 1.0 | -2.2 | 4.2 |
| VAS Back Pain | 143 | 67.7 | 23.5 | 75.0 | 0.0 | 100.0 | 150 | 65.6 | 25.3 | 70.0 | 0.0 | 100.0 | 2.1 | -3.5 | 7.7 |
| VAS Worse Leg Pain | 143 | 70.3 | 24.9 | 78.0 | 0.0 | 100.0 | 150 | 70.6 | 23.7 | 74.0 | 0.0 | 100.0 | -0.3 | -5.8 | 5.3 |
| VAS Left Leg Pain | 143 | 54.0 | 33.5 | 62.0 | 0.0 | 100.0 | 150 | 47.3 | 35.4 | 50.0 | 0.0 | 100.0 | 6.7 | -1.3 | 14.6 |
| VAS Right Leg Pain | 143 | 44.4 | 35.3 | 46.0 | 0.0 | 100.0 | 150 | 49.6 | 33.2 | 55.0 | 0.0 | 100.0 | -5.2 | -13.1 | 2.7 |
| SF12 v2 Physical Component | 140 | 27.4 | 6.9 | 27.4 | 8.5 | 47.3 | 148 | 27.3 | 7.4 | 27.6 | 9.5 | 52.3 | 0.1 | -1.6 | 1.7 |
| SF12 v2 Mental Component | 140 | 43.4 | 12.2 | 44.1 | 15.6 | 70.0 | 148 | 45.9 | 13.0 | 47.7 | 7.6 | 74.6 | -2.4 | -5.3 | 0.5 |
| Notes: † Device group differences and 95% confidence intervals (CI) for group differences. | | | | | | | | | | | | | | | |

Additional demographic characteristics for the treated population are shown in TABLE 5.

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TABLE 5 - Summary of Baseline and Demographic - Categorical Variables - mITT Population

| | PearlMatrix™ Bone Graft | | Autologous bone | | PearlMatrix™ Bone Graft - Autologous Bone¹ | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | n | % | n | % | Diff (%) | LB | UB |
| Number of subjects | 143 | | 150 | | | | |
| Males | 66 | 46.2 | 75 | 50.0 | -3.8 | -15.3 | 7.6 |
| Females | 77 | 53.8 | 75 | 50.0 | | | |
| Ethnicity | n | % | n | % | Diff (%) | LB | UB |
| Hispanic or Latino | 8 | 5.6 | 2 | 1.3 | 4.3 | 0.1 | 8.5 |
| Not Hispanic or Latino | 135 | 94.4 | 148 | 98.7 | | | |
| Race (check all that apply) | n | % | n | % | Diff (%) | LB | UB |
| American Indian/Alaskan Native | 0 | 0.0 | 1 | 0.7 | -0.7 | -2.0 | 0.6 |
| Asian | 0 | 0.0 | 1 | 0.7 | -0.7 | -2.0 | 0.6 |
| Black | 7 | 4.9 | 14 | 9.3 | -4.4 | -10.3 | 1.4 |
| Native Hawaiian/Pacific Islander | | | | | | | |
| White | 136 | 95.1 | 134 | 89.3 | 5.8 | -0.3 | 11.8 |
| Other | | | | | | | |
| Is subject of child-bearing potential? | n | % | n | % | Diff (%) | LB | UB |
| Yes | 11 | 14.3 | 7 | 9.3 | 5.0 | -5.3 | 15.2 |
| No | 66 | 85.7 | 68 | 90.7 | | | |
| Note: ¹ Device group differences and 95% confidence intervals (CI) for group differences. | | | | | | | |

A summary of baseline risk factors is provided in TABLE 6. As noted previously, the subject randomizations were further stratified as either normal or higher risk. Subjects with one of the following were defined to be in the higher-risk stratum: nicotine use defined as once per day or more of cigarettes, vaping, patches, or chewing tobacco; $\mathrm{BMI} \geq 30 \mathrm{~kg} / \mathrm{m}^2$; and/or diabetes defined as confirmed diagnosis of Type 2 diabetes. All other subjects were defined to be in the normal risk stratum. Overall, the percentage of both higher and normal risk subjects was similar in both arms. The most frequently observed higher risk factor for both treatment groups were obesity with $50.3\%$ (72/143) for the PearlMatrix™ Bone Graft arm and $48.7\%$ (73/150) for the Control arm. Among subjects with nicotine use, there were 15 subjects with use 6 or more times per day in the control arm (62.5% of subjects with any nicotine use). There were 6 such subjects in the PearlMatrix™ Bone Graft arm (37.5% of subjects with any nicotine use).

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TABLE 6 - Summary of Baseline Risk Factors - mITT Population

| | PearlMatrix™ Bone Graft | | Autologous bone | | PearlMatrix™ Bone Graft - Autologous Bone¹ | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| High Risk? | n | % | n | % | Diff (%) | LB | UB |
| Yes | 89 | 62.2 | 95 | 63.3 | -1.1 | -12.2 | 10.0 |
| No | 54 | 37.8 | 55 | 36.7 | | | |
| Number of Risk Factors² | n | % | n | % | Diff (%) | LB | UB |
| 0 | 54 | 37.8 | 55 | 36.7 | 0.678 | | |
| 1 | 66 | 46.2 | 67 | 44.7 | | | |
| 2 | 21 | 14.7 | 25 | 16.7 | | | |
| 3 | 2 | 1.4 | 3 | 2.0 | | | |
| Diabetes Type 2 | n | % | n | % | Diff (%) | LB | UB |
| Yes | 26 | 18.2 | 29 | 19.3 | -1.2 | -10.1 | 7.8 |
| No | 117 | 81.8 | 121 | 80.7 | | | |
| Nicotine Use: (Cigarettes, vaping, patches, chewing tobacco) | | | | | | | |
| Yes | 16 | 11.2 | 24 | 16.0 | -4.8 | -12.6 | 3.0 |
| No | 127 | 88.8 | 126 | 84.0 | | | |
| Nicotine Use: Times per day² | n | % | n | % | Diff (%) | LB | UB |
| 1 | 4 | 25.0 | 5 | 20.8 | 0.266 | | |
| 2 | 1 | 6.3 | 2 | 8.3 | | | |
| 3 | 2 | 12.5 | 1 | 4.2 | | | |
| 4 | 1 | 6.3 | 0 | 0.0 | | | |
| 5 | 2 | 12.5 | 1 | 4.2 | | | |
| 6 or more | 6 | 37.5 | 15 | 62.5 | | | |
| Obesity (BMI ≥ 30 k/m²) | n | % | n | % | Diff (%) | LB | UB |
| Yes | 72 | 50.3 | 73 | 48.7 | 1.7 | -9.8 | 13.1 |
| No | 71 | 49.7 | 77 | 51.3 | | | |
| Note: ¹ Device group differences and 95% confidence intervals (CI) for group differences. ² Wilcoxon rank sum test for ordinal data | | | | | | | |

1. Surgery and Operative Characteristics

The operative characteristics recorded included surgical approach (open versus minimally invasive), duration of surgery, level operated, blood loss, decortication of facet joints. Variables are similar between groups. A summary of the surgery and operative characteristics is provided in TABLE 7. The most common surgical level was L4-L5 and the second most common was L5-S1 in both arms.

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TABLE 7 – Surgery and Operative Characteristics - mITT Population

| | PearlMatrix™ Bone Graft
N=142 | Control
N=148 |
| --- | --- | --- |
| Surgery Level | n (%) | n (%) |
| L1-L2 | 0 (0.0%) | 1 (0.7%) |
| L2-L3 | 6 (4.2%) | 2 (1.4%) |
| L3-L4 | 12 (8.5%) | 20 (13.5%) |
| L4-L5 | 88 (62.0%) | 88 (59.5%) |
| L5-S1 | 36 (25.4%) | 37 (25.0%) |
| Facet Joint Decortication | 92 (64.8%) | 104 (70.3%) |
| Surgical Procedure | | |
| Open | 84 (59.2%) | 75 (50.7%) |
| Minimally Invasive | 58 (40.8%) | 73 (49.3%) |
| | | |
| Duration of Anesthesia (min) | 238.5 ± 59.8
Range: 114.0-480.0
N=141 | 243.5 ± 61.3
Range: 160.0-461.0
N=148 |
| Duration of Surgery (min) | 172.9 ± 51.6
Range: 71.0-382.0
N=141 | 178.5 ± 54.7
Range: 79.0-360.0
N=147 |
| Blood Loss (mL) | 145.5 ± 143.8
Range: 10.0-1100.0
N=142 | 158.0 ± 161.2
Range: 5.0-1000.0
N=148 |

D. Safety and Effectiveness Results

1. Safety Results

The analysis of safety was based on the “As Treated” (AT) cohort of 290 patients/procedures available for the 24-month evaluation. The primary analysis set for the study is the modified intention-to-treat (mITT) analysis set; however, safety data presented alone (and outside the composite primary endpoint) are usefully presented for the AT set to reflect data associated with specific events. Adverse events are reported in TABLES 8-13.

Adverse events that occurred in the PMA clinical study:

Adverse events were defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, whether or not related to the investigational medical device. Adverse events were summarized as counts and per patient incidence by device, overall, and by categories of adverse events including specific AE, relatedness, severity, and whether or not the AE was serious.

All adverse events were collected and recorded, regardless of whether they were believed to be related to the device or anticipated. This included the following:

- Adverse Device Effects (ADEs) – adverse event related to the use of an investigational medical device.

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- Serious Adverse Events (SAEs) – an adverse event that led to death; led to serious deterioration in the health of the subject, that either resulted in: a life-threatening illness or injury; a permanent impairment of a body structure or a body function; in-patient or prolonged hospitalization; medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function; led to fetal distress, fetal death or congenital abnormality/birth defect.

- Unanticipated Adverse Device Effects (UADEs) – any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

- Device deficiency – inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety, or performance.

The proportion of subjects with any reported adverse event, serious adverse event, adverse event of special interest, or death by 24 months in the AT population is shown in TABLE 8. The proportion of subjects with any adverse event was 86.5% in the PearlMatrix™ Bone Graft arm (122/141) and 81.2% in the Control arm (121/149), a difference of 5.3% (95% CI -3.1, 13.8). Regarding serious adverse events (SAEs), the proportion of subjects with any device/procedure-related SAEs was 26.2% in the PearlMatrix™ Bone Graft arm (37/141) and 13.4% in the Control arm (20/149), a difference of 12.8% (95% CI 3.7, 21.9). When considering SAEs that were adjudicated as device-related, the proportion was 5.7% in the PearlMatrix™ Bone Graft arm (8/141) and 4.7% in the Control arm (7/149), a difference of 1.0% (95% CI -4.1, 6.1). When considering SAEs that were adjudicated as procedure-related, the proportion was 26.2% in the PearlMatrix™ Bone Graft arm (37/141) and 13.4% in the Control arm (20/149), a difference of 12.8% (95% CI 3.7, 21.9).

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TABLE 8 - Summary of Adverse Event Rates in the AT Population

| | PearlMatrix™ Bone Graft (N=141) | | | Autologous Bone (N=149) | | | PearlMatrix™ Bone Graft -Autologous¹ | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Events | n | % | Events | n | % | Diff (%) | LB | UB |
| Any adverse event (per patient) | 607 | 122 | 86.5 | 617 | 121 | 81.2 | 5.3 | -3.1 | 13.8 |
| Any device related AE² | 28 | 22 | 15.6 | 22 | 20 | 13.4 | 2.2 | -5.9 | 10.3 |
| Any procedure related AE² | 189 | 80 | 56.7 | 141 | 59 | 39.6 | 17.1 | 5.8 | 28.5 |
| Any SAE | 68 | 45 | 31.9 | 76 | 44 | 29.5 | 2.4 | -8.2 | 13.0 |
| SAE, device/procedure related | 45 | 37 | 26.2 | 24 | 20 | 13.4 | 12.8 | 3.7 | 21.9 |
| SAE, device/procedure related that resulted in SSI | 17 | 11 | 7.8 | 4 | 4 | 2.7 | 5.1 | 0.0 | 10.3 |
| SAE, device related | 8 | 8 | 5.7 | 8 | 7 | 4.7 | 1.0 | -4.1 | 6.1 |
| SAE, device related that resulted in SSI | 7 | 7 | 5.0 | 4 | 4 | 2.7 | 2.3 | -2.2 | 6.7 |
| SAE, procedure related | 45 | 37 | 26.2 | 24 | 20 | 13.4 | 12.8 | 3.7 | 21.9 |
| SAE, procedure related that resulted in SSI | 17 | 11 | 7.8 | 4 | 4 | 2.7 | 5.1 | 0.0 | 10.3 |
| Any AE of Special Interest | 23 | 18 | 12.8 | 31 | 19 | 12.8 | 0.0 | -7.7 | 7.7 |
| Deaths | 2 | 2 | 1.4 | 1 | 1 | 0.7 | 0.7 | -1.6 | 3.1 |
| Notes: ¹ Unadjusted device group differences and 95% confidence intervals (CI) for group differences. ² Device or Procedure relatedness includes possible, probably, and definitely related. | | | | | | | | | |

The proportion of subjects with any reported adverse event, serious adverse event, adverse event of special interest, or death by 24 months in the "Per Protocol" (PP) population is shown in TABLE 9.

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TABLE 9 - Summary of Adverse Event Rates in the PP Population

| | PearlMatrix™ Bone Graft (N=137) | | | Autologous Bone (N=143) | | | PearlMatrix™ Bone Graft vs. Autologous Bone¹ | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Events | n | % | Events | n | % | Diff (%) | LB | UB |
| Any adverse event (per patient) | 586 | 118 | 86.1 | 602 | 116 | 81.1 | 5.0 | -3.6 | 13.7 |
| Any device related AE² | 28 | 22 | 16.1 | 22 | 20 | 14.0 | 2.1 | -6.3 | 10.5 |
| Any procedure related AE² | 179 | 76 | 55.5 | 136 | 55 | 38.5 | 17.0 | 5.5 | 28.5 |
| Any SAE | 66 | 44 | 32.1 | 72 | 41 | 28.7 | 3.4 | -7.3 | 14.2 |
| SAE, device/procedure related | 43 | 36 | 26.3 | 22 | 18 | 12.6 | 13.7 | 4.5 | 22.9 |
| SAE, device/procedure related that resulted in SSI | 17 | 11 | 8.0 | 4 | 4 | 2.8 | 5.2 | -0.1 | 10.5 |
| SAE, device related | 8 | 8 | 5.8 | 8 | 7 | 4.9 | 0.9 | -4.3 | 6.2 |
| SAE, device related that resulted in SSI | 7 | 7 | 5.1 | 4 | 4 | 2.8 | 2.3 | -2.3 | 6.9 |
| SAE, procedure related | 43 | 36 | 26.3 | 22 | 18 | 12.6 | 13.7 | 4.5 | 22.9 |
| SAE, procedure related that resulted in SSI | 17 | 11 | 8.0 | 4 | 4 | 2.8 | 5.2 | -0.1 | 10.5 |
| Any AE of Special Interest | 23 | 18 | 13.1 | 31 | 19 | 13.3 | -0.1 | -8.1 | 7.8 |
| Deaths | 2 | 2 | 1.5 | 1 | 1 | 0.7 | 0.8 | -1.7 | 3.2 |
| Notes: ¹ Unadjusted device group differences and 95% confidence intervals (CI) for group differences. ² Device or Procedure relatedness includes possible, probably, and definitely related. | | | | | | | | | |

TABLE 10 shows a summary of the number of adverse events by body system over time for the AT population, regardless of severity, seriousness, or relatedness to the device or procedure. For both groups, musculoskeletal and connective tissue disorders and nervous system disorders were the most common adverse events reported at each post-operative visit; the number of these adverse events was comparable between groups.

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TABLE 10 - Adverse Events by Body System and Preferred Term Over Time

| | Day of Surgery to 30 Days | | >30 to 90 Days | | >90 to 180 Days | | >180 to 365 Days | | >365 to 730 Days | | >730 Days | | Totals | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Adverse Event Description | I | C | I | C | I | C | I | C | I | C | I | C | I | C |
| BLOOD AND LYMPHATIC SYSTEM DISORDERS | 4 | 3 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 6 | 7 |
| CARDIAC DISORDERS | 5 | 3 | 2 | 1 | 0 | 2 | 3 | 0 | 2 | 3 | 0 | 7 | 12 | 16 |
| CONGENITAL, FAMILIAL AND GENETIC DISORDERS | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| EAR AND LABYRINTH DISORDERS | 1 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 3 |
| ENDOCRINE DISORDERS | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 5 | 0 |
| GASTROINTESTINAL DISORDERS | 6 | 3 | 4 | 2 | 5 | 2 | 2 | 5 | 4 | 8 | 1 | 9 | 22 | 29 |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 3 | 7 | 2 | 4 | 5 | 0 | 1 | 2 | 2 | 2 | 1 | 4 | 14 | 19 |
| HEPATOBILIARY DISORDERS | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 3 | 2 |
| IMMUNE SYSTEM DISORDERS | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
| INFECTIONS AND INFESTATIONS | 14 | 2 | 10 | 3 | 8 | 10 | 8 | 12 | 13 | 6 | 5 | 12 | 58 | 45 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS | 26 | 14 | 5 | 6 | 3 | 4 | 9 | 11 | 19 | 13 | 7 | 14 | 69 | 62 |
| INVESTIGATIONS | 4 | 1 | 2 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 2 | 9 | 4 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | 27 | 19 | 17 | 31 | 40 | 21 | 27 | 42 | 59 | 71 | 27 | 51 | 197 | 235 |
| NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) | 0 | 1 | 2 | 0 | 0 | 2 | 0 | 4 | 0 | 3 | 0 | 4 | 2 | 14 |
| NERVOUS SYSTEM DISORDERS | 20 | 16 | 13 | 13 | 14 | 14 | 20 | 16 | 12 | 18 | 20 | 18 | 99 | 95 |
| PSYCHIATRIC DISORDERS | 4 | 1 | 4 | 0 | 0 | 0 | 1 | 0 | 1 | 3 | 1 | 0 | 11 | 4 |
| RENAL AND URINARY DISORDERS | 7 | 4 | 1 | 0 | 0 | 2 | 1 | 0 | 1 | 2 | 4 | 3 | 14 | 11 |
| REPRODUCTIVE SYSTEM AND BREAST DISORDERS | 0 | 2 | 0 | 0 | 2 | 1 | 2 | 2 | 1 | 0 | 0 | 1 | 5 | 6 |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | 7 | 2 | 2 | 1 | 3 | 0 | 0 | 4 | 6 | 4 | 3 | 3 | 21 | 14 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | 3 | 1 | 1 | 2 | 3 | 1 | 1 | 3 | 2 | 2 | 0 | 3 | 10 | 12 |
| SURGICAL AND MEDICAL PROCEDURES | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 2 | 1 |
| VASCULAR DISORDERS | 8 | 7 | 1 | 1 | 2 | 2 | 1 | 1 | 1 | 5 | 2 | 4 | 15 | 20 |
| PRODUCT ISSUES | 1 | 0 | 2 | 0 | 2 | 0 | 4 | 0 | 0 | 1 | 0 | 0 | 9 | 1 |

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TABLE 11 shows the counts and percentages of patients with device-related adverse events by body system, regardless of seriousness or severity. Device-related adverse events most frequently resulted in musculoskeletal and connective tissue disorders for both groups (PearlMatrix™ Bone Graft, 12 subjects (8.5%); Control, 11 subjects (7.4%)). Overall, back pain (PearlMatrix™ Bone Graft, 5 subjects (3.5%); Control, 3 subjects (2.0%)), radiculopathy (PearlMatrix™ Bone Graft, 3 subjects (2.1%); Control, 2 subjects (1.3%)) and pseudoarthrosis (PearlMatrix™ Bone Graft, 2 subjects (1.4%); Control, 4 subjects (2.7%)) were the most frequently occurring device-related adverse events. Device-related adverse events occurred more often in the PearlMatrix™ Bone Graft arm.

For nervous system disorders, device-related adverse events occurred in 6 subjects for both the PearlMatrix™ Bone Graft arm (7 events, 4.3% of subjects) and in the Control arm (6 events, 4.0% of subjects). For the Control arm, device-related adverse events occurred more often in the injury, poisoning, and procedural complications category versus the PearlMatrix™ Bone Graft arm.

For the PearlMatrix™ Bone Graft arm, device-related adverse events occurred more often in the infections and infestations, and musculoskeletal and connective tissue disorders categories versus the Control arm. In the infections and infestations category, there one (1) instance of device-related infection (wound infection) in one (1) patient of the PearlMatrix™ Bone Graft arm, while there were no instances of infection in the Control arm. In the musculoskeletal and connective tissue disorders category, 12 events occurred in 12 subjects of the PearlMatrix™ Bone Graft arm (arthralgia (1), back pain (5), lumbar spinal stenosis (1), pain in extremity (1), pseudoarthrosis (2), spondylolisthesis (1), vertebral foraminal stenosis (1)), while 11 events occurred in 11 subjects of the Control arm (back pain (3), disc space narrowing (1), lumbar spinal stenosis (2), musculoskeletal pain (1), and pseudoarthrosis (4)).

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TABLE 11 – Counts and Percentages of Subjects with Device-Related Adverse Events by Body System in the AT Population

| | PearlMatrix™ Bone Graft (N=141) | | | Autologous Bone (N=149) | | | PearlMatrix™ Bone Graft vs Autologous Bone† | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Adverse Event Description | No. of Events | No. of Pts. | % of Pts. | No. of Events | No. of Pts. | % of Pts. | Diff | LB | UB |
| INFECTIONS AND INFESTATIONS | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| wound infection | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| INJURY, POISONING & PROCEDURAL COMPLICATIONS | 3 | 3 | 2.1 | 5 | 5 | 3.4 | -1.2 | -5.9 | 3.2 |
| graft complication | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| incomplete spinal fusion | 1 | 1 | 0.7 | 4 | 4 | 2.7 | -2.0 | -6.1 | 1.5 |
| lumbar vertebral fracture | 0 | 0 | 0.0 | 1 | 1 | 0.7 | -0.7 | -3.8 | 2.0 |
| seroma | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| MUSCULOSKELETAL & CONNECTIVE TISSUE DISORDERS | 12 | 12 | 8.5 | 11 | 11 | 7.4 | 1.1 | -5.4 | 8.0 |
| arthralgia | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| back pain | 5 | 5 | 3.5 | 3 | 3 | 2.0 | 1.5 | -2.7 | 6.4 |
| intervertebral disc space narrowing | 0 | 0 | 0.0 | 1 | 1 | 0.7 | -0.7 | -3.8 | 2.0 |
| lumbar spinal stenosis | 1 | 1 | 0.7 | 2 | 2 | 1.3 | -0.6 | -4.2 | 2.7 |
| musculoskeletal pain | 0 | 0 | 0.0 | 1 | 1 | 0.7 | -0.7 | -3.8 | 2.0 |
| pain in extremity | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| pseudarthrosis | 2 | 2 | 1.4 | 4 | 4 | 2.7 | -1.3 | -5.5 | 2.7 |
| spondylolisthesis | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| vertebral foraminal stenosis | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| NERVOUS SYSTEM DISORDERS | 7 | 6 | 4.3 | 6 | 6 | 4.0 | 0.2 | -4.9 | 5.5 |
| hypoaesthesia | 1 | 1 | 0.7 | 1 | 1 | 0.7 | 0.0 | -3.2 | 3.3 |
| paraesthesia | 2 | 2 | 1.4 | 0 | 0 | 0.0 | 1.4 | -1.2 | 5.1 |
| piriformis syndrome | 0 | 0 | 0.0 | 1 | 1 | 0.7 | -0.7 | -3.8 | 2.0 |
| radiculopathy | 3 | 3 | 2.1 | 2 | 2 | 1.3 | 0.8 | -3.0 | 5.0 |
| sciatica | 1 | 1 | 0.7 | 1 | 1 | 0.7 | 0.0 | -3.2 | 3.3 |
| spinal claudication | 0 | 0 | 0.0 | 1 | 1 | 0.7 | -0.7 | -3.8 | 2.0 |
| RENAL AND URINARY DISORDERS | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| micturition urgency | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| PRODUCT ISSUES | 4 | 3 | 2.1 | 0 | 0 | 0.0 | 2.1 | -0.5 | 6.1 |
| device dislocation | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| device fastener issue | 2 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| implant subsidence | 1 | 1 | 0.7 | 0 | 0 | 0.0 | 0.7 | -1.9 | 3.9 |
| Subjects with at least 1 adverse event | | 22 | | | 20 | | | | |
| Notes:† 95% exact binomial confidence interval. | | | | | | | | | |

TABLE 12 shows the counts and percentages of patients with procedure-related adverse events by body system regardless of seriousness or severity. Procedure-related adverse events most frequently resulted in injury, poisoning, and procedural complications (PearlMatrix™ Bone Graft, 23 subjects (16.3%); Control, 22 subjects (14.8%)), musculoskeletal and connective tissue disorders (PearlMatrix™ Bone Graft, 40 subjects (28.4%); Control, 30 subjects (20.1%)), and nervous system disorders (PearlMatrix™ Bone Graft, 33 subjects (23.4%); Control, 21 subjects (14.1%)). Overall, dural tears (PearlMatrix™ Bone Graft, 6 subjects (4.3%); Control, 2 subjects (1.3%)), pain in extremity (PearlMatrix™

PMA P240001: FDA Summary of Safety and Effectiveness Data

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Bone Graft, 6 subjects (4.3%); Control, 3 subjects (2.0%), radiculopathy (PearlMatrix™ Bone Graft, 9 subjects (6.4%); Control, 8 subjects (5.4%), and back pain (PearlMatrix™ Bone Graft, 25 subjects (17.7%); Control, 14 subjects (9.4%)) were the most frequently occurring procedure-related adverse events.

Differences between the PearlMatrix™ Bone Graft and Control arms were present for procedure-related adverse events. Postoperative wound infections in the "Infections and Infestations" category had more adverse events in the PearlMatrix™ Bone Graft arm versus the Control arm; the group difference was 2.8 (95% CI 0.2, 7.2). Back pain in the musculoskeletal and connective tissue disorders category also had more adverse events in the PearlMatrix™ Bone Graft arm versus the Control arm, where back pain was greater in the PearlMatrix™ Bone Graft arm compared to the control, the group difference was 8.3 (95% CI 0.3, 16.7). The nervous system disorders category had more adverse events in the PearlMatrix™ Bone Graft arm versus the Control arm, the group difference was 9.3 (95% CI 0.2, 18.5), where patients reported headaches more often in the PearlMatrix™ Bone Graft arm compared to the control with a group difference of 2.8 (95% CI 0.2, 7.2). Lastly, the product issue category had more adverse events in the PearlMatrix™ Bone Graft arm versus the control with a group difference of 5.0 (95% CI 1.0, 10.3), where patients experienced implant subsidence more often in the PearlMatrix™ Bone Graft arm compared to the control with a group difference of 2.8 (95% CI 0.2, 7.2).

PMA P240001: FDA Summary of Safety and Effectiveness Data
26

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TABLE 12 - Patients with Procedure-Related Adverse Events by Body System in the AT Population

| | PearlMatrix N=141 | | | Autologous Bone N=149 | | | PearlMatrix vs Autologous | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Adverse Event Description | No. of Events | No. of Pts. | % of Pts. | No. of Events | No. of Pts. | % of Pts. | Diff | LB | UB |
| BLOOD AND LYMPHATIC SYSTEM DISORDERS | 3.0 | 3.0 | 2.1 | 4.0 | 3.0 | 2.0 | 0.1 | -3.9 | 4.4 |
| anaemia | 2.0 | 2.0 | 1.4 | 1.0 | 1.0 | 0.7 | 0.7 | -2.5 | 4.6 |
| haemorrhagic anaemia | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| leukocytosis | 1.0 | 1.0 | 0.7 | 2.0 | 2.0 | 1.3 | -0.6 | -4.2 | 2.7 |
| CARDIAC DISORDERS | 3.0 | 2.0 | 1.4 | 3.0 | 3.0 | 2.0 | -0.6 | -4.6 | 3.3 |
| acute myocardial infarction | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| arrhythmia | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| atrial fibrillation | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| cardiac arrest | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| myocardial infarction | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| tachycardia | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| EAR AND LABYRINTH DISORDERS | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| hypoacusis | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| ENDOCRINE DISORDERS | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| hypothyroidism | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| GASTROINTESTINAL DISORDERS | 7.0 | 6.0 | 4.3 | 5.0 | 3.0 | 2.0 | 2.2 | -2.1 | 7.3 |
| abdominal pain | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| anal incontinence | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| colitis | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| constipation | 3.0 | 3.0 | 2.1 | 2.0 | 2.0 | 1.3 | 0.8 | -3.0 | 5.0 |
| eructation | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| nausea | 2.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |
| vomiting | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 2.0 | 2.0 | 1.4 | 8.0 | 8.0 | 5.4 | -4.0 | -9.1 | 0.4 |
| ill-defined disorder | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| impaired healing | 1.0 | 1.0 | 0.7 | 2.0 | 2.0 | 1.3 | -0.6 | -4.2 | 2.7 |
| medical device site pain | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| peripheral swelling | 0.0 | 0.0 | 0.0 | 2.0 | 2.0 | 1.3 | -1.3 | -4.8 | 1.4 |
| pyrexia | 0.0 | 0.0 | 0.0 | 3.0 | 3.0 | 2.0 | -2.0 | -5.9 | 0.7 |
| INFECTIONS AND INFESTATIONS | 14.0 | 11.0 | 7.8 | 4.0 | 4.0 | 2.7 | 5.1 | -0.1 | 11.2 |
| clostridial sepsis | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| corona virus infection | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| diverticulitis | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| gastroenteritis | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| pneumonia | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| postoperative wound infection | 5.0 | 4.0 | 2.8 | 0.0 | 0.0 | 0.0 | 2.8 | 0.2 | 7.2 |
| staphylococcal infection | 1.0 | 1.0 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |
| urinary tract infection | 3.0 | 3.0 | 2.1 | 0.0 | 0.0 | 0.0 | 2.1 | -0.5 | 6.1 |
| urinary tract infection bacterial | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| wound infection | 2.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |

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PMA P240001: FDA Summary of Safety and Effectiveness Data

| Adverse Event Description | PearlMatrix N=141 | | | Autologous Bone N=149 | | | PearlMatrix vs Autologous | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | No. of Events | No. of Pts. | % of Pts. | No. of Events | No. of Pts. | % of Pts. | Diff | LB | UB |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS | 25.0 | 23.0 | 16.3 | 24.0 | 22.0 | 14.0 | 1.5 | -7.0 | 10.2 |
| adjacent segment degeneration | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| contusion | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| corneal abrasion | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| device deployment issue | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| dural tear | 6.0 | 6.0 | 4.3 | 2.0 | 2.0 | 1.3 | 2.9 | -1.1 | 8.0 |
| fall | 0.0 | 0.0 | 0.0 | 3.0 | 2.0 | 1.3 | -1.3 | -4.8 | 1.4 |
| graft complication | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| incision site dermatitis | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| incision site erythema | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| incision site haemorrhage | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| incision site pain | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| incision site pruritus | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| incomplete spinal fusion | 2.0 | 2.0 | 1.4 | 4.0 | 4.0 | 2.7 | -1.3 | -5.5 | 2.7 |
| ligament sprain | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| lumbar vertebral fracture | 1.0 | 1.0 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |
| overdose | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| post procedural fever | 0.0 | 0.0 | 0.0 | 2.0 | 2.0 | 1.3 | -1.3 | -4.8 | 1.4 |
| post procedural persistent drain fluid | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| post-traumatic pain | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| postoperative wound complication | 1.0 | 1.0 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |
| procedural complication | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| procedural pain | 3.0 | 3.0 | 2.1 | 1.0 | 1.0 | 0.7 | 1.5 | -1.8 | 5.5 |
| procedural site reaction | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| seroma | 2.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |
| wound dehiscence | 1.0 | 1.0 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |
| wound secretion | 2.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |
| INVESTIGATIONS | 2.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| blood pressure increased | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| heart rate increased | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| METABOLISM AND NUTRITION DISORDERS | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| hyponatraemia | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |

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| | PearlMatrix N=141 | | | Autologous Bone N=149 | | | PearlMatrix vs Autologous | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Adverse Event Description | No. of Events | No. of Pts. | % of Pts. | No. of Events | No. of Pts. | % of Pts. | Diff | LB | UB |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERIS | 67.0 | 40.0 | 28.4 | 52.0 | 30.0 | 20.1 | 8.2 | -1.8 | 18.2 |
| arthralgia | 3.0 | 3.0 | 2.1 | 3.0 | 3.0 | 2.0 | 0.1 | -3.9 | 4.4 |
| back pain | 27.0 | 25.0 | 17.7 | 16.0 | 14.0 | 9.4 | 8.3 | 0.3 | 16.7 |
| cervical spinal stenosis | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| chondromalacia | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| facet joint syndrome | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| temporoacetabular impingement | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| groin pain | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| intervertebral disc protrusion | 3.0 | 3.0 | 2.1 | 1.0 | 1.0 | 0.7 | 1.5 | -1.8 | 5.5 |
| intervertebral disc space narrowing | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| lumbar spinal stenosis | 1.0 | 1.0 | 0.7 | 6.0 | 6.0 | 4.0 | -3.3 | -8.0 | 0.4 |
| muscle spasms | 6.0 | 5.0 | 3.5 | 3.0 | 2.0 | 1.3 | 2.2 | -1.8 | 6.9 |
| muscle swelling | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| muscle tightness | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| muscular weakness | 2.0 | 2.0 | 1.4 | 3.0 | 2.0 | 1.3 | 0.1 | -3.6 | 3.9 |
| musculoskeletal pain | 2.0 | 2.0 | 1.4 | 1.0 | 1.0 | 0.7 | 0.7 | -2.5 | 4.6 |
| musculoskeletal stiffness | 1.0 | 1.0 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |
| myalgia | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| myofascial pain syndrome | 2.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |
| neck pain | 3.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |
| pain in extremity | 6.0 | 6.0 | 4.3 | 4.0 | 3.0 | 2.0 | 2.2 | -2.1 | 7.3 |
| pseudarthrosis | 2.0 | 2.0 | 1.4 | 5.0 | 5.0 | 3.4 | -1.9 | -6.5 | 2.1 |
| sacroiliitis | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| scoliosis | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| spinal column stenosis | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| spinal osteoarthritis | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| spondylolisthesis | 1.0 | 1.0 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |
| trigger finger | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| vertebral foraminal stenosis | 1.0 | 1.0 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |

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PMA P240001: FDA Summary of Safety and Effectiveness Data

| Adverse Event Description | PearlMatrix N=141 | | | Autologous Bone N=149 | | | PearlMatrix vs Autologous | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | No. of Events | No. of Pts. | % of Pts. | No. of Events | No. of Pts. | % of Pts. | Diff | LB | UB |
| NERVOUS SYSTEM DISORDERS | 410 | 33.0 | 23.4 | 250 | 21.0 | 14.1 | 9.3 | 0.2 | 18.5 |
| cerebrospinal fluid leakage | 10 | 10 | 0.7 | 2.0 | 2.0 | 1.3 | -0.6 | -4.2 | 2.7 |
| cerebrovascular accident | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| dizziness | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| dysarthria | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| headache | 4.0 | 4.0 | 2.8 | 0.0 | 0.0 | 0.0 | 2.8 | 0.2 | 7.2 |
| hemiparesis | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| hypoaesthesia | 6.0 | 6.0 | 4.3 | 5.0 | 4.0 | 2.7 | 1.6 | -3.2 | 6.7 |
| lumbar radiculopathy | 4.0 | 4.0 | 2.8 | 1.0 | 1.0 | 0.7 | 2.2 | -1.2 | 6.6 |
| migraine | 2.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |
| nervous system disorder | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| neuralgia | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| paraesthesia | 4.0 | 4.0 | 2.8 | 2.0 | 2.0 | 1.3 | 1.5 | -2.4 | 6.0 |
| peroneal nerve palsy | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| piriformis syndrome | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| radicular pain | 2.0 | 2.0 | 1.4 | 1.0 | 1.0 | 0.7 | 0.7 | -2.5 | 4.6 |
| radiculopathy | 9.0 | 9.0 | 6.4 | 8.0 | 8.0 | 5.4 | 1.0 | -4.8 | 7.1 |
| sciatica | 10 | 10 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |
| sensory disturbance | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| spinal claudication | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| syncope | 2.0 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| tremor | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| PSYCHIATRIC DISORDERS | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| delirium | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| RENAL AND URINARY DISORDERS | 4.0 | 4.0 | 2.8 | 4.0 | 3.0 | 2.0 | 0.8 | -3.3 | 5.3 |
| micturition urgency | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| pollakiuria | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| urinary incontinence | 10 | 10 | 0.7 | 2.0 | 2.0 | 1.3 | -0.6 | -4.2 | 2.7 |
| urinary retention | 2.0 | 2.0 | 1.4 | 1.0 | 1.0 | 0.7 | 0.7 | -2.5 | 4.6 |
| REPRODUCTIVE SYSTEM AND BREAST DISORDERS | 10 | 10 | 0.7 | 2.0 | 2.0 | 1.3 | -0.6 | -4.2 | 2.7 |
| genital paraesthesia | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| scrotal pain | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| testicular swelling | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | 2.0 | 2.0 | 1.4 | 1.0 | 1.0 | 0.7 | 0.7 | -2.5 | 4.6 |
| acute respiratory failure | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| atelectasis | 10 | 10 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| respiratory failure | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |

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| | PearlMatrix N=141 | | | Autologous Bone N=149 | | | PearlMatrix vs Autologous | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Adverse Event Description | No. of Events | No. of Pts. | % of Pts. | No. of Events | No. of Pts. | % of Pts. | Diff | LB | UB |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | 2.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |
| hyperhidrosis | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| rash maculo-papular | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| VASCULAR DISORDERS | 5.0 | 5.0 | 3.5 | 6.0 | 6.0 | 4.0 | -0.5 | -5.5 | 4.6 |
| deep vein thrombosis | 1.0 | 1.0 | 0.7 | 2.0 | 2.0 | 1.3 | -0.6 | -4.2 | 2.7 |
| embolism | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| haematoma | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| hypotension | 2.0 | 2.0 | 1.4 | 3.0 | 3.0 | 2.0 | -0.6 | -4.6 | 3.3 |
| orthostatic hypertension | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 0.7 | -0.7 | -3.8 | 2.0 |
| PRODUCT ISSUES | 9.0 | 8.0 | 5.7 | 1.0 | 1.0 | 0.7 | 5.0 | 1.0 | 10.3 |
| device breakage | 1.0 | 1.0 | 0.7 | 1.0 | 1.0 | 0.7 | 0.0 | -3.2 | 3.3 |
| device dislocation | 1.0 | 1.0 | 0.7 | 0.0 | 0.0 | 0.0 | 0.7 | -1.9 | 3.9 |
| device fastener issue | 3.0 | 2.0 | 1.4 | 0.0 | 0.0 | 0.0 | 1.4 | -1.2 | 5.1 |
| implant subsidence | 4.0 | 4.0 | 2.8 | 0.0 | 0.0 | 0.0 | 2.8 | 0.2 | 7.2 |
| Subjects with at least 1 adverse event | . | 80.0 | . | . | 59.0 | . | . | . | . |

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A summary of serious adverse events, regardless of device or procedure-relatedness, is provided in TABLE 13. The definition of serious is any adverse event that led to death; led to serious deterioration in the health of the subject, that either resulted in: a life-threatening illness or injury; a permanent impairment of a body structure or a body function; in-patient or prolonged hospitalization; medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function; led to fetal distress, fetal death or congenital abnormality/birth defect.

TABLE 13 – Serious Adverse Events

| Adverse Event | PearlMatrix n=141 | | | Control n=149 | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Subjects | % | Events | Subjects | % | Events |
| Any Adverse Event | 45 | 31.9 | 68 | 44 | 29.5 | 76 |
| Dural tear | 2 | 1.4 | 2 | 0 | 0.0 | 0 |
| Graft complication | 0 | 0.0 | 0 | 0 | 0.0 | 0 |
| Lumbar vertebral fracture | 1 | 0.7 | 1 | 1 | 0.7 | 1 |
| Pain in extremity | 2 | 1.4 | 2 | 1 | 0.7 | 1 |
| Pseudarthrosis | 1 | 0.7 | 1 | 2 | 1.3 | 2 |
| Incomplete spinal fusion | 1 | 0.7 | 1 | 2 | 1.3 | 2 |
| Cerebrospinal fluid leakage | 1 | 0.7 | 1 | 2 | 1.3 | 2 |
| Lumbar radiculopathy | 4 | 2.8 | 4 | 1 | 0.7 | 1 |
| Back pain | 6 | 4.3 | 6 | 1 | 0.7 | 1 |
| Radicular pain | 0 | 0.0 | 0 | 1 | 0.7 | 1 |
| Radiculopathy | 2 | 1.4 | 2 | 0 | 0.0 | 0 |
| Sciatica | 0 | 0.0 | 0 | 0 | 0.0 | 0 |
| Spinal claudication | 0 | 0.0 | 0 | 1 | 0.7 | 1 |
| Device dislocation | 0 | 0.0 | 0 | 0 | 0.0 | 0 |
| Implant subsidence | 1 | 0.7 | 1 | 0 | 0.0 | 0 |
| Postoperative wound infection | 1 | 0.7 | 1 | 0 | 0.0 | 0 |
| Wound infection | 2 | 1.4 | 2 | 0 | 0.0 | 0 |
| Heterotopic ossification | 0 | 0.0 | 0 | 0 | 0.0 | 0 |
| Osteolysis | 0 | 0.0 | 0 | 0 | 0.0 | 0 |
| Seroma | 0 | 0.0 | 0 | 0 | 0.0 | 0 |
| Others^{1} | 23 | 16.3 | 44 | 33 | 22.1 | 64 |

¹Others includes blood and lymphatic system disorders; cardiac disorders; congenital, familial and genetic disorders; ear and labyrinth disorders; eye disorders; gastrointestinal disorders; general disorders; hepatobiliary disorders; immune system disorders; infections and infestations; injury, poisoning and procedural complications; investigations; metabolism and nutrition disorders; musculoskeletal and connective tissue disorders; neoplasms benign, malignant and unspecified; nervous system disorders; psychiatric disorders; renal and urinary disorders; reproductive system and breast disorders; respirator, thoracic and mediastinal disorders; skin and subcutaneous tissue disorders; surgical and medical procedures; and vascular disorders. Includes one (1) unclassified event in the PearlMatrix™ Bone Graft arm.

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PMA P240001: FDA Summary of Safety and Effectiveness Data

# 2. Safety and Effectiveness Results

The analysis of effectiveness was based on the 293-subject mITT data set at the 24-month time point. Key effectiveness outcomes are presented in TABLES 14 to 23. The mITT was the primary analysis set with the PP and AT analysis sets presented as sensitivity analysis.

## Primary Endpoint – Clinical Composite Success

The primary endpoint was the Month 24 Composite Clinical Success (CCS), a composite of five (5) measures of safety and effectiveness at 24 months. CCS was defined as all the following at month 24:

- No index level secondary surgical intervention;
- Achievement of fusion;
- At least a 15-point improvement in ODI from baseline (on a 100-point scale);
- No new or worsening, persistent neurological deficit relative to baseline; and
- No serious device-related adverse events.

Note that randomization was performed within risk group for each center. To account for the randomization within risk group, the estimated difference and its standard error were determined for the higher risk and normal risk groups separately. Then, the overall group difference was estimated as a weighted average of the stratum-specific group differences using Mantel-Haenszel weights that are designed to minimize the variance of the pooled stratified estimate of the treatment group difference. Because the differences and confidence intervals are adjusted for the risk groups, the risk-adjusted differences are not necessarily equal to the differences in observed rates.

The CCS in the mITT population is shown in TABLE 14, where 55.4% of the PearlMatrix™ Bone Graft arm (67/121) and 36.4% of the Control arm (47/129) achieved CCS. The risk-adjusted difference between groups for CCS was 18.9% (90% CI 8.7%, 29.1%). Since the one-sided p-value for testing non-inferiority is 0.0000002, it can be concluded that PearlMatrix™ Bone Graft was clinically non-inferior to control. In higher risk stratum, the group difference was 14.2% (90% CI 0.1% to 27.4%). In the lower risk group, the group difference was 25.9% (10.1% to 41.8%). Thus, it was concluded that the PearlMatrix™ Bone Graft was non-inferior to the control with respect to the composite clinical success, a composite of five (5) measures of safety and effectiveness, at 24 months in a randomized clinical trial, in the mITT analysis set.

There are two pre-specified secondary endpoints with multiplicity controls: superiority in CCS and superiority in time-to-fusion. The one-sided p-value for testing superiority was 0.0012 (The two superiority endpoints were each tested at

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1-sided 0.025/2=0.0125). Since 0.0012 < 0.0125, it can be concluded that PearlMatrix™ Bone Graft was superior to control. A 95% two-sided confidence interval for the group difference was 6.8% to 31.1%.

Both the non-inferiority result and the superiority result were primarily driven by the fusion rate in the Control arm, which was substantively lower than the event rates for the other four variables within the Control arm. By contrast ODI improvements, neurological outcomes, and serious device-related adverse event rates had similar event rates both between arms and within the same arm relative to each other. The PearlMatrix™ Bone Graft arm had a higher rate of index-level secondary surgeries than the Control arm. Since CCS requires success on all variables, the minimum value among the variables sets the maximum possible value for CCS. Overall results on the composite endpoint should be evaluated together with performance on the individual elements of the composite as shown in TABLE 14.

Missing data for the primary composite clinical success (CCS) endpoint was addressed using multiple imputation (MI). The fully conditional specification (FCS) approach was used to produce 20 complete multiple imputed data sets. To implement the MI, simplified CCS endpoints were determined at Months 6 and 12 as available. The FCS included these simplified CCS and the set of variables that were pre-specified for stratified analyses including risk strata, amount of bone graft material (over 8cc or not), gender, whether age over 65 years, race being non-white or white, whether investigator declared financial interest, whether facet joint involved, whether spine intervention level was above L4-L5, and whether the procedure was open vs closed. The simplified CCS at Month 6 and Month 12 were based on whether or not the subject experienced a secondary surgical intervention (SSI), fusion status, and an ODI improvement of ≥15. TABLE 14 provides the multiple imputation results.

PMA P240001: FDA Summary of Safety and Effectiveness Data
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TABLE 14 - Percentages of Subjects Achieving Month 24 Success in the mITT Population

| | PearlMatrix™ Bone Graft (N=143) | | | Autologous Bone (N=150) | | | PearlMatrix™ Bone Graft - Autologous Bone | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | N | n | % | N | n | % | Diff (%) | LB¹ | UB |
| Composite Clinical Success⁶ | 121 | 67 | 55.4 | 129 | 47 | 36.4 | 18.9 | 8.7 | 29.1 |
| (1) No index level secondary surgical intervention to Study Day 730 | 143 | 130 | 90.9 | 150 | 146 | 97.3 | -6.3 | -11.7 | -1.0 |
| (2) Achievement of fusion by Month 24 visit (Fusion is defined as evidence of bridging trabecular bone between the vertebral bodie…