GORE VIABAHN VBX BALLOON EXPANDABLE ENDOPROSTHESIS

P160021 · W. L. Gore & Associates, Inc. · PRL · Jan 27, 2017 · Cardiovascular

Device Facts

• Record ID: P160021
• Device Name: GORE VIABAHN VBX BALLOON EXPANDABLE ENDOPROSTHESIS
• Applicant: W. L. Gore & Associates, Inc.
• Product Code: PRL · Cardiovascular
• Decision Date: Jan 27, 2017
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Intended Use

The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is indicated for the treatment of de novo or restenotic lesions found in iliac arteries with reference vessel diameters ranging from 5mm - 13mm and lesion lengths up to 110mm, including lesions at the aortic bifurcation.

Device Story

Balloon-expandable stent graft; consists of 316L stainless steel rings encapsulated in fluoropolymer film; features CBAS® Heparin Surface (covalent end-point attached heparin). Premounted on PTA balloon catheter delivery system; compatible with 0.035" guidewires. Used in interventional radiology/vascular surgery settings; physician-operated. Physician gains guidewire access; pre-dilates lesion; positions device; inflates balloon to deploy stent; deflates and removes catheter. Post-placement dilatation possible with secondary balloon. Supports vessel wall; restores blood flow; treats iliac artery occlusive disease. Benefits include improved functional status and reduced need for revascularization.

Clinical Evidence

Prospective, multi-center, single-arm clinical study (VBX FLEX, IDE G120232) of 134 patients. Primary endpoint: composite of MAE (death, MI, TLR, major amputation) at 9 months. Results: 2.3% MAE rate (95% CI: 0.5%, 6.5%), significantly lower than 17.0% performance goal (p<0.001). Secondary endpoints included patency and functional status (WIQ, EQ-5D) improvements. No device-related SAEs reported through 9 months.

Technological Characteristics

Materials: 316L stainless steel, fluoropolymer film, CBAS® Heparin Surface (porcine-derived). Sensing/Actuation: Balloon-expandable. Dimensions: 5-11mm nominal diameter, 15-79mm length. Connectivity: None. Sterilization: Ethylene oxide. Software: None.

Indications for Use

Indicated for symptomatic (Rutherford Category 2-4) patients with de novo or restenotic lesions in common and/or external iliac arteries (5-13mm diameter, ≤110mm length). Contraindicated in patients with known hypersensitivity to heparin or history of Heparin-Induced Thrombocytopenia (HIT) type II.

Regulatory Classification

Identification

For the treatment of de novo or restenotic lesions found in iliac arteries

Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

## I. GENERAL INFORMATION

Device Generic Name: Stent, Iliac

Device Trade Name: GORE® VIABAHN® VBX Balloon
Expandable Endoprosthesis

Device Product Code: NIO

Applicant’s Name and Address: W.L. Gore &amp; Associates, Inc.
3250 West Kiltie Lane, P.O. Box 2400
Flagstaff, AZ 86005

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P160021

Date of FDA Notice of Approval: 1/27/2017

Priority Review: No

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## II. INDICATIONS FOR USE

The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is indicated for the treatment of de novo or restenotic lesions found in iliac arteries with reference vessel diameters ranging from 5mm - 13mm and lesion lengths up to 110mm, including lesions at the aortic bifurcation.

## III. CONTRAINDICATIONS

Do not use the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis in patients with known hypersensitivity to heparin, including those patients who have had a previous incident of Heparin-Induced Thrombocytopenia (HIT) type II.

## IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis labeling.

## V. DEVICE DESCRIPTION

The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis system is comprised of two main components:

1) The balloon-expandable stent graft (also referred to as the endoprosthesis or covered stent).
2) A balloon catheter delivery system.

### Balloon Expandable Stent Graft

The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis consists of two structural elements: 316L surgical grade stainless steel and a fluoropolymer film, see Figure 1. The fluoropolymer film is present on both sides of the stainless steel rings (encapsulating the rings) and serves as a linkage between the discrete rings. The CBAS® Heparin Surface on the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis consists of stable, covalent, end-point attached heparin of porcine origin.

Figure 1: GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis

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# The Balloon Catheter Delivery System

The endoprosthesis is premounted on a delivery system equipped with a Percutaneous Transluminal Angioplasty (PTA) semi-compliant balloon designed for deploying the stent graft via balloon inflation (Figure 2). The balloon is covered with a thin fluoropolymer/elastomer film to maximize retention of the endoprosthesis during tracking and deployment of the device. The delivery system has two radiopaque balloon markers embedded in the shaft (denoting the effective balloon length) to aid in the placement of the endoprosthesis. The delivery system is compatible with $0.035''$ ( $0.89\mathrm{mm}$ ) guidewires, and is available in 80 and $135\mathrm{cm}$ catheter lengths. The delivery system can be used for initial stent placement and post stent dilatation. The diameter of the endoprosthesis may be increased post-placement beyond the nominal diameter by expanding with a larger diameter secondary balloon.

Figure 2: GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis Delivery System

# CARMEDA BioActive Surface (CBAS) Heparin Surface

The CBAS Heparin Surface consists of heparin molecules that are covalently bonded to all stent surfaces by an "end-point attachment" method. USP heparin sodium API of porcine origin is used in the manufacture of the CBAS Heparin Surface. The heparin sodium API has been tested and certified to meet United States Pharmacopeia (USP) / European

Pharmacopoeia (EP) requirements. The heparin sodium API is entirely of North American origin and is subsequently derivatized by a proprietary process established by Carmeda AB, Uplands Väsby, Sweden. Heparin bioactivity (ability to bind antithrombin III) is retained in the binding process due to the end-point covalent attachment that does not interfere with the heparin active site.

The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis system is available in a variety of configurations as outlined in Table 1.

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Table 1: Complete List of GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis Configurations

| Stent Labeled/ Nominal Diameter (mm) | Crimped Stent Length (mm) | Introducer Sheath Size (Fr) | Guidewire Diameter | Max. Post-Dilated Stent Diameter1 (mm) | Catheter Length (cm) | RBP2 (atm / kPa) |
| --- | --- | --- | --- | --- | --- | --- |
| 5 | 15, 19, 29, 39, 59, 79 | 7 | 0.035" (0.89 mm) | 8 | 80, 135 | 15 / 1520 |
| 6 | 15, 19, 29, 39, 59, 79 | 7 | 0.035" (0.89 mm) | 8 | 80, 135 | 15 / 1520 |
| 7 | 15, 19, 29, 39, 59, 79 | 7 | 0.035" (0.89 mm) | 11 | 80, 135 | 15 / 1520 |
| 8 | 29, 39, 59 | 7 | 0.035" (0.89 mm) | 11 | 80, 135 | 13 / 1317 |
| | 79 | 8 | | | | |
| 8L | 29, 39 | 7 | 0.035" (0.89 mm) | 16 | 80, 135 | 13 / 1317 |
| | 59, 79 | 8 | | | | |
| 9 | 29, 39, 59, 79 | 8 | 0.035" (0.89 mm) | 13 | 80, 135 | 13 / 1317 |
| 10 | 29, 39, 59, 79 | 8 | 0.035" (0.89 mm) | 13 | 80, 135 | 13 / 1317 |
| 11 | 29, 39, 59, 79 | 8 | 0.035" (0.89 mm) | 16 | 80, 135 | 12 / 1216 |

1 Secondary balloon required to post-dilate the stent beyond its nominal deployed diameter (secondary balloon not included).
2 RBP is Rated Burst Pressure.

# Principles of Operation

For implantation, the physician gains guidewire access to the target location. The physician pre-dilates the target lesion by inflating a PTA balloon catheter and makes angiographic measurements to select the appropriate size endoprosthesis. The catheter mounted balloon expandable stent is delivered to the target location over the guidewire and positioned at the target lesion. The stent is deployed from the delivery catheter by inflating the system to the pressure needed for the desired diameter. When fully deployed and seated, the stent supports the target vessel. The delivery catheter balloon is deflated and removed, or can be used for post stent dilatation. The diameter of the endoprosthesis may be increased post-placement beyond the nominal diameter by expanding with a larger diameter secondary balloon.

# VI. ALTERNATIVE PRACTICES AND PROCEDURES

Alternative practices and procedures for treatment of iliac artery occlusive disease include lifestyle modification and disease management, pharmacotherapy, surgical treatment, percutaneous transluminal angioplasty, and stenting with an iliac-indicated product.

All alternatives possess advantages and disadvantages, and patients should discuss potential alternatives with their physician to identify which treatment method may be most appropriate for them.

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# VII. MARKETING HISTORY

At the time of this approval, the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis has not been marketed in the United States or any foreign country.

# 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 device:

Procedure Related: As with all procedures that utilize techniques for introducing a catheter into a vessel, complications may be expected. These complications include, but are not limited to: access site infection; entry site bleeding and/or hematoma; vessel thrombosis, occlusion, pseudoaneurysm, and trauma to the vessel wall (including rupture or dissection); distal embolization; arteriovenous fistula formation; transient or permanent contrast induced renal failure; renal toxicity; sepsis; shock; radiation injury; myocardial infarction; fever; pain; malposition; malapposition; inflammation; and/or death. A possible complication which may occur in conjunction with the use of heparin: Heparin-Induced Thrombocytopenia type II.

Device Related: Complications and adverse events can occur when using any endovascular device. These complications include, but are not limited to: hematoma; stenosis, thrombosis or occlusion; distal embolism; side branch occlusion; vessel wall trauma and/or rupture; false aneurysm; infection; inflammation; fever and/or pain in the absence of infection; deployment failure; migration; and device failure. A possible complication which may occur in conjunction with the use of any heparin-containing product: Heparin-Induced Thrombocytopenia type II.

For the specific adverse events that occurred in the clinical study, please see Section X below.

# IX. SUMMARY OF PRECLINICAL STUDIES

## A. Biocompatibility Studies

Biocompatibility testing was conducted on the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis in accordance with applicable Good Laboratory Practices (21 CRF §58) and ISO 10993-1: 2009, Biological Evaluation of Medical Devices and Guidance for Industry and FDA Staff: Non-Clinical Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems (April 18, 2010). Tests were conducted separately on product manufactured, packaged and sterilized using the materials and procedures intended for the marketed product consisting of the 1) delivery system and 2) endoprosthesis.

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The delivery system is classified as an externally communicating device in limited contact (&lt; 24 hrs) with circulating blood. The endoprosthesis is classified as an implant device in permanent contact (&gt; 30 days) with blood. A summary of the biocompatibility testing conducted can be found in Table 2 below.

Table 12: Summary of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis Biocompatibility Testing

| Test Performed | Test Description | Stent | Delivery System | Results |
| --- | --- | --- | --- | --- |
| Cytotoxicity | ISO MEM Elution Assay with L-929 Mouse Fibroblast Cells | X | X | Non-toxic |
| Sensitization | ISO Guinea Pig Maximization | X | X | Non-sensitizing |
| Irritation | ISO Intracutaneous Reactivity | X | X | Non-irritating |
| Pyrogenicity | Material-Mediated Pyrogenicity | X | X | Non-pyrogenic |
| Acute Systemic Toxicity | ISO Systemic Toxicity Study | X | X | Non-toxic |
| Subchronic Toxicity | 14 Day Repeat Dose Intravascular and Intraperitoneal Toxicity Study | X | N/A | Non-toxic |
| Implantation | Intra-Muscular Implantation Study – 4 Weeks | X | N/A | Non-toxic |
| | Intra-Muscular Implantation Study – 13 Weeks | X | N/A | Non-toxic |
| | Intra-Vascular Implantation Study | X^{a} | N/A | Non-toxic |
| Hemocompatibility | ASTM Hemolysis Study (Direct and Indirect Contact) | X | X | Non-hemolytic |
| | Complement Activation Assay (C3a and SC5b-9) | X | X | Not a complement activator |
| | In Vivo Thrombogenicity Study | X^{a} | X^{b} | Non-thrombogenic |
| Genotoxicity | Bacterial Reverse Mutation (Ames) Assay | X | X | Non-mutagenic |
| | Mouse Lymphoma Assay | X | X | Non-genotoxic |
| | Mouse Micronucleus Assay | X | X | Non-genotoxic |

a Evaluated as part of the animal studies outlined in Section C, below.
b Delivery system tested in the absence and presence of anticoagulation. Labeling recommends procedural anticoagulation.

Stent thrombogenicity was evaluated as part of other in vivo studies conducted to evaluate safety and performance of the device in a vascular implant location, as described in Section C, below.

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The omission of chronic toxicity and carcinogenicity testing for the stent was supported by information regarding the starting materials, processing of the finished device, toxicity and genotoxicity biocompatibility testing, and toxicity data from the literature.

The information provided demonstrates that the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is biocompatible and suitable for the intended use.

## B. In vitro Bench Testing

In vitro bench testing to support the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis was developed based on the device risk assessment and is consistent with FDA Non-Clinical Tests and Recommended Labeling of Intravascular Stents and Associated Delivery Systems, April 18, 2010 and its addendum, Select Updates for Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems, August 30, 2013.

The relevant in vitro tests outlined in the guidance document and included in support of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis are summarized in Table 3 below.

| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Stent Engineering Testing | | | |
| Material Composition | Characterize the stent material composition to ensure it is acceptable for the intended use. | ASTM F138-08 | The stent material conforms to implant material standards. |
| Corrosion Resistance | To evaluate the susceptibility of the metallic materials of the endoprosthesis to corrosion. | The breakdown potential, rest potential, protection potential (if available from the testing), and Eb-Er values will be reported for all samples for characterization purposes.
For post-fatigue samples, corrosion resistance was evaluated on devices after pulsatile fatigue testing (see below) and a microscopic examination was performed to inspect for evidence of fretting, pitting, or crevice corrosion. | The endoprosthesis exhibits acceptable corrosion resistance based on testing per ASTM F2129-15.
For post-fatigue samples, there was no evidence of fractures, abrasion, corrosion, or other irregularities. |

Table 23: Summary of In Vitro Test Results

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| Test | Purpose | Acceptance Criteria | | Results |
| --- | --- | --- | --- | --- |
| Dimensional Verification (mounted stent length, profile, deployed stent length, wall thickness) | To determine the mounted stent length, profile, deployed stent length, wall thickness. | The deployed stent length, wall thickness, and profile must be characterized. The mounted length must be equal to nominal length ± the greater of either 1 mm or 5% | | All measurements were characterized. The mounted stent length met the requirement. |
| Foreshortening (nominal) | To assess the decrease in length of the endoprosthesis between the catheter-mounted condition and the deployed condition (foreshortening). | Nominal Inner Diameter | Foreshortening Requirement | PASS |
| | | 5-6 mm | ≤10% | |
| | | 7-8 mm | ≤15% | |
| | | 9-11 mm | <20% | |
| Foreshortening (tapered) | To assess the foreshortening of the endoprosthesis deployed in a tapered configuration. | For characterization only. | | Tapered foreshortening was successfully characterized. |
| Stent Integrity | To verify the endoprosthesis has no clinically significant defects or flaws after deployment. | The endoprosthesis must have no tears, cuts, holes, breaks, stent fractures, delaminations, or exposed stents. | | PASS |
| Stent Coating Integrity | To assess the surface coating integrity of the endoprosthesis. | For characterization only. | | Stent coating integrity was successfully characterized. |
| Recoil and Uniformity of Expansion | To assess the elastic recoil after deployment and difference between the largest and smallest diameters of the endoprosthesis (uniformity of expansion) | Average Recoil: ≤10% Uniformity of Expansion: ≤0.8 mm | | PASS |
| Radial Strength / Radial Stiffness | To determine the radially applied load at which permanent deformation occurs and to characterize the radial stiffness | Endoprosthesis must have sufficient radial strength to withstand clinically relevant forces. The radial stiffness must be characterized. | | Endoprostheses met the established acceptance criteria for radial strength and radial stiffness was characterized. |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Mechanical Properties | To characterize the mechanical properties of the stainless steel stent to ensure they are acceptable for the intended use. | The tested stainless steel stent must exhibit a tensile stress at yield, elongation, and tensile stress at maximum load that is acceptable for the intended use. | PASS |
| Strain and Fatigue Analysis/Finite Element Analysis (FEA) | To determine the location and magnitude of the maximum principal stresses in the stents, under expected clinical use conditions, through the use of Finite Element Analysis (FEA). | Strains were calculated through the use of a validated FEA model. | The stress condition of the worst case device size fell in the safe region on a Goodman diagram for 316L stainless steel. |
| Accelerated Durability Testing | To evaluate the long-term structural integrity of the endoprosthesis under cyclic loading conditions that represent the in vivo environment. | The endoprosthesis must exhibit acceptable simulated 10 year fatigue durability as evidenced by no damage that compromises device function. Stent fractures and other durability observations will be recorded and assessed. | All endoprostheses met the acceptance criteria. There were no fractures, tears, cuts, holes, or delamination. |
| Particulate Evaluation | To assess the amount of particulation for the endoprosthesis. | For characterization purposes only. | Acute particulation was successfully characterized. |
| MR Compatibility | To evaluate the MRI safety and compatibility of the stent. | The implant must not present additional risk to the patient when exposed to static magnetic field strengths of 1.5 and 3.0 Tesla. | The stent does not pose additional risk to patients and may be labeled MR Conditional according to ASTM 2503. |
| Radiopacity | Determine the visibility of the endoprosthesis and catheter delivery system under fluoroscopy. | The catheter delivery system must enable fluoroscopic visualization of the delivery catheter. The endoprosthesis must be visible under fluoroscopy. | PASS |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Crush Resistance | Determine the force at which permanent deformation occurs under a load applied perpendicular to the longitudinal axis of the device. | Load per length at collapse must meet the criteria specified as acceptable for the intended use. | PASS |
| Delivery System Engineering Testing | | | |
| Kink Resistance | To determine the minimum radius of curvature the device can withstand without kinking | The endoprosthesis must be able to recover its original size and shape after testing for bend radius.The endoprosthesis must exhibit an average bend radius that is less than or equivalent to the average bend radius for the closest competitive balloon-expandable stents | PASS |
| Dimensional Verification (Profile) | To verify the maximum diameter of the catheter delivery system and mounted endoprosthesis | The profile must be characterized. Passage of devices through appropriately sized introducer sheaths was evaluated in accessory component compatibility testing (below). | The device profile was successfully characterized. |
| Dimensional Verification (Working Length) | To determine the delivery catheter working length, which enables treatment of the intended site. | The delivery catheter working length must meet the following criteria:For 135cm catheter lengths133 - 140 cmFor 80cm catheter lengths78 - 85 cm | PASS |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Dimensional Verification (Catheter Shaft ID, Catheter Shaft OD) | To assess the catheter shaft ID, and catheter shaft OD of the endoprosthesis. | Catheter shaft ID and catheter shaft OD measurements must be characterized. | Catheter shaft ID and catheter shaft OD were successfully characterized. |
| Delivery, Deployment, and Retraction (Accessory Component Compatibility) | To assess compatibility of the device with accessory devices. | The device must be compatible with accessories, including appropriately sized guidewire, flushing syringe, inflation device, and appropriately sized introducer sheath with at least 95% confidence that 95% of the population will pass the requirement. | PASS |
| Delivery, Deployment, and Retraction (Deployment System Reliability, Trackability, Pushability, Stent Retention, Dislodgement) | To assess the ability of the catheter delivery system to deliver the endoprosthesis to the intended location and deploy the endoprosthesis. | Trackability, pushability, stent dislodgement during withdrawal, visual inspection (delivery system), visual inspection (deployed stent), and migration resistance must meet the claim of at least 95% confidence that 95% of the population pass the requirement. Stent retention must meet the claim of at least 95% confidence that 98% of the population pass the requirement. | PASS |
| Delivery, Deployment, and Retraction (Deployment System Accuracy) | To assess the deployment system accuracy of the endoprosthesis. | The location of the endoprosthesis post deployment must be within ± 2 mm of the target location. | PASS |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Kissing Stent Simulated Use | To characterize the aspects of simulated use that are potentially affected by use of the device in a kissing stent configuration. | For characterization only. | Kissing stent simulated use was successfully characterized. |
| Balloon Rated Burst Pressure | To determine the calculated Rated Burst Pressure (RBP) of the balloon when inside the endoprosthesis for each diameter. | The calculated RBP must be characterized for each diameter. | The calculated Rated Burst Pressure for each device diameter was successfully characterized. |
| Balloon Fatigue | To determine the ability of the balloon, when inside of the endoprosthesis, to withstand repeated inflation cycles to the maximum recommended pressure. | All samples must successfully withstand 10 inflation cycles to the labeled Rated Burst Pressure without failing. | PASS |
| Balloon Compliance | To assess the relationship between endoprosthesis inner diameter and delivery system pressure. | The relationship between implant inner diameter and balloon inflation pressure must be characterized. | The relationship between implant inner diameter and balloon inflation pressure was successfully characterized. |
| Balloon Dogboning | To assess the balloon dogboning of the delivery system. | The diameter of the balloon extending beyond the ends of the endoprosthesis must not be visibly larger than the Endoprosthesis outer diameter at the rated burst pressure for each test device. | PASS |
| Balloon Inflation and Deflation Times | To determine the time required to completely inflate and deflate the balloon when inside of the endoprosthesis. | The inflation and deflation times must meet the criteria specified as acceptable for the intended use. | PASS |

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| Test | Purpose | Acceptance Criteria | Results |
| --- | --- | --- | --- |
| Catheter Bond Strengths | To determine the bond strength of the joints and fixed connections of the delivery system. | The delivery system must have sufficient strength to maintain its function during access, deployment, and retraction. | PASS |
| Catheter Delivery System Flexibility & Kink | To verify the catheter delivery system is able to reliably track through tortuous, clinically relevant anatomy without kinking. | The catheter must withstand a bend radius of < 11 mm without kinking. | PASS |
| Torque Strength | To determine the torque required to cause failure of the joints and/or fixed connections in delivery system. | The proximal hub must rotate at least 3 rotations without mechanical damage or failure when the distal end is fixed. | PASS |
| Stent Securement for Unsecured Sheaths | To determine the strength of the connection between the endoprosthesis and the delivery system. | The endoprosthesis must not dislodge from the delivery system during advancement through an introducer sheath and the tortuous model to the target location. At least 95% confidence that 98% of the population passes the requirement. | PASS |

# C. Animal Studies

Acute and chronic in vivo animal studies were conducted to evaluate the safety and performance of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis. Seven preclinical studies (2 acute, 5 chronic) evaluated the in vivo performance of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis in appropriate animal models. All of these studies were performed in compliance with Good Laboratory Practices (GLP) per 21 CFR 58 at AALAS-accredited facilities. A marketed balloon-expandable stent-graft was employed as a control device in two of the chronic studies. Table 4 summarizes the results of the GLP studies conducted on finished, sterile devices. The results of the animal studies support the safety and performance of the device.

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Table 34: Summary Results of the GLP Animal Studies

| Study Type | Number of Stents / Number of Animals / Implant Location | Testing Summary |
| --- | --- | --- |
| Acute (0 day) performance study in Yucatan Mini Swine | 6 study devices / 3 swine / external iliac arteries (single) | All devices met the pre-established acceptance criteria (primary endpoint) for device delivery and deployment, including trackability, deployment, accuracy and withdrawal. No fractures or migrations were detected. PASS |
| Acute (0 day) performance study in Yucatan Mini Swine | 12 study devices / 2 swine / carotid arteries (single), iliac arteries (single), left femoral artery (single), left deep femoral artery (single) and the distal abdominal aorta (overlapped) | All devices met the pre-established acceptance criteria (primary endpoint) including trackability, deployment, accuracy, withdrawal, radiopacity, migration, catheter thrombus formation, and apposition. PASS |
| Chronic (90 day) Safety Study in Suffolk Cross Ovine | 4 study devices, 4 control stents / 4 ovine / external iliac arteries (single) | The primary endpoint (patency) was achieved with The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis and control device as all devices remained patent at 90 days. No statistical difference in max percent diameter stenosis was observed between the groups. PASS
Both test and control devices lacked endothelialization in the middle sections of the device.
Luminal Thrombus was scored at 0.75 on a scale of 0 to 4 with 0 being absent and 4 being occluded.
No gross evidence of distal embolization for test and control devices.
No evidence of dissections or aneurysms were noted for test or control devices. |

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| Chronic (90 day) Safety Study in Polypay Ovine | 18 study devices / 6 ovine / external iliac arteries (6 single devices, 12 devices overlapped in pairs) | The primary endpoint (patency) was achieved with The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis as all devices remained patent at 90 days. PASS

The single and overlapped devices lacked endothelialization in the middle sections.

Luminal Thrombus was scored at 0.61 on a scale of 0 to 4 with 0 being absent and 4 being occluded.

No gross evidence of distal embolization for single and overlapped devices

No evidence of dissections or aneurysms were noted for single and overlapped devices |
| --- | --- | --- |
| Chronic (180 day) Safety Study in Polypay and Finn Ovine | 12 study devices / 6 ovine / external iliac arteries (single) | The primary endpoint (patency) was achieved with The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis as all devices remained patent at 180 days PASS

The devices lacked endothelialization in the middle sections.

Luminal Thrombus was scored at 0.86 on a scale of 0 to 4 with 0 being absent and 4 being occluded.

No gross evidence of distal embolization of the devices were noted.

No evidence of dissections or aneurysms were noted for any of the devices |

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| Chronic (180 day) Safety Study in Canine Mixed Breed Hounds | 12 study devices / 6 canine / external iliac arteries (single) | The primary endpoint (patency) was achieved with The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis as all devices remained patent at 180 days PASS

The devices lacked endothelialization in the middle sections.

Luminal Thrombus was scored at 0.31 on a scale of 0 to 4 with 0 being absent and 4 being occluded.

No gross evidence of distal embolization of the devices were noted.

No evidence of dissections or aneurysms were noted for any of the devices |
| --- | --- | --- |
| Chronic (90 day) Safety Study in Canine Mixed Breed Hounds | 6 study devices, 6 control stents / 4 canine / 8 single devices in carotid arteries, 4 single devices in external iliac arteries | The primary endpoint (patency) was achieved with The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis and control device as all devices remained patent at 90 days. PASS

All other measured parameters performed as intended for stents placed in the iliac arteries.

The test devices lacked endothelialization in the middle sections.

Luminal Thrombus of the test devices was scored at 0.50 on a scale of 0 to 4 with 0 being absent and 4 being occluded.

No gross evidence of distal embolization for test or control devices.

No evidence of dissections or aneurysms were noted for test or control devices |

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D. Sterilization

The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is sterilized by ethylene oxide. Validation of the sterilization method to ensure a Sterility Assurance Level (SAL) of 10⁻⁶ has been conducted in accordance with ISO 11135-1:2007 Sterilization of health care products- Ethylene oxide-Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices.

E. Packaging and Product Shelf Life

Packaging qualification and device verification testing was performed on the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis at baseline and on aged product. The device is placed in a high-density polyethylene (HDPE) coil then sealed in a foil-Tyvek pouch primary pouch, and a poly-Tyvek secondary pouch. The packaged device is then placed in a carton. A shelf life of 3 years has been established for the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis based on product and package shelf life testing.

X. SUMMARY OF PRIMARY CLINICAL STUDY

A prospective, multi-center, single arm clinical study in the United States (US) and New Zealand was conducted to establish a reasonable assurance of safety and effectiveness of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis for the treatment of arterial occlusive disease in patients with de novo or restenotic lesions in the common and/or external iliac arteries. The data produced from the VBX FLEX clinical study under IDE # G120232 were the basis for a PMA approval decision for the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis. A summary of the VBX FLEX clinical study is presented below.

A. Study Design

Patients were treated between December 17, 2013 and August 12, 2015. The database for this PMA reflected data collected through June 9, 2016 and included 140 patients. There were 27 investigational sites.

The VBX FLEX clinical study under IDE G120232 was a prospective, multicenter, single-arm clinical study to evaluate the safety and efficacy of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis for the treatment of arterial occlusive disease in patients with de novo or restenotic lesions in the common and/or external iliac arteries.

The primary study endpoint was a composite of major adverse events (MAE) defined as device – or procedure-related death within 30 days; myocardial infarction (MI) within 30 days; amputation above the metatarsals in the treated leg, resulting from a vascular event, within 9 months; or target lesion revascularization (TLR) within 9 months. The objective of the VBX FLEX clinical study was to demonstrate that the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is safe and effective for treatment of iliac artery

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disease by comparing the composite primary endpoint result to a pre-specified Performance Goal (PG) of 17.0%.

The study population included symptomatic (Rutherford Category 2-4) patients with angiographic confirmation of either de novo or restenotic unilateral or bilateral occlusive disease in the common and/or external iliac arteries, with a total treated lesion length of ≤110 mm and vessel diameters between approximately 5 mm and 13 mm. Patients were included who presented with up to two discrete lesions requiring treatment, either one lesion per side for patients presenting with bilateral disease, or two lesions on the same side. All subjects could be treated with up to three GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis. Eligible patients in the study included those presenting with tortuous iliacs, severe lesion calcification, total occlusions, and those determined to need direct stenting (pre-dilatation optional) and/or kissing stent treatment at the aortic bifurcation. 134 subjects meeting all eligibility criteria were enrolled across 26 sites in U.S. and 1 site in New Zealand. Following enrollment/baseline and the index procedure, all evaluable subjects were assessed at 1 and 9 months post-index procedure.

The statistical analysis plan prospectively specified that subjects meeting all of the eligibility criteria would be used for analysis of study endpoints. A sensitivity analysis would be performed for testing the primary hypothesis in the intent-to-treat (ITT) population, which included all enrolled subjects, as well as the per-protocol (PP) population which included only those subjects who met the study inclusion criteria.

All adverse events were reviewed and adjudicated by the Clinical Events Committee (CEC). The CEC determined the final relationship of each adverse event and categorized each adverse event as device-related, index procedure-related, disease-related (PAD), unrelated to device, procedure, or disease, or unknown relationship. The severity of each adverse event was determined by the site investigator based on the ISO 14155 definition of serious and non-serious adverse events. The Data Safety and Monitoring Board (DSMB) provided oversight of safety trends and reviewed site reported protocol deviations and source data related to subject eligibility. Independent core laboratories evaluated angiographic and ultrasound imaging obtained during the study procedure and at follow-up visits.

## 1. Clinical Inclusion and Exclusion Criteria

Enrollment in the VBX FLEX clinical study was limited to patients who met the following inclusion criteria:

### Subject Inclusion Criteria

1. Patient is at least 18 years old;
2. Patient is male, infertile female, or female of childbearing potential practicing an acceptable method of preventing pregnancy;

NOTE: Women of childbearing potential must have a negative β- (beta) hCG pregnancy test within 7 days of index procedure.

3. Patient or legal representative is willing to give written informed consent;

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4. Patient is capable of complying with protocol requirements, including all follow-up visits;
5. Patient has symptomatic claudication or rest pain without tissue loss (Rutherford Categories 2-4).

## Angiographic Inclusion Criteria

1. Patient has de novo or restenotic target lesion(s) in the common and/or external iliac artery;
2. Patient has one or more regions of stenosis ≥ 50% in the target vessel, based on visual estimate;
3. Patient has a target vessel diameter visually estimated to be approximately between 5 mm and 13 mm;
4. Patient has adequate ipsilateral blood flow including at least one sufficient (&lt;50% stenotic) infrapopliteal run-off vessel not requiring intervention (per side to be intervened on).
5. Patient has a total target lesion length visually estimated to be ≤110 mm which can be treated with a maximum of three GORE® VIABAHN® VBX Balloon Expandable Endoprostheses;
6. Patient has no more than two discrete ipsilateral lesions that can be treated with no more than three GORE® VIABAHN® VBX Balloon Expandable Endoprostheses [OR] Patient has bilateral disease consisting of only one target lesion per side that can be treated with no more than a total of three GORE® VIABAHN® VBX Balloon Expandable Endoprostheses;
7. Patient has the device advanced across the target lesion(s) and positioned for deployment.

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

## Subject Exclusion Criteria

1. Patient has a life expectancy of less than 1 year;
2. Patient has a known allergy to stent graft components, including stainless steel or heparin;
3. Patient has a known intolerance to antiplatelet, anticoagulant, or thrombolytic medications that would prevent compliance with the protocol;
4. Patient has a condition (unrelated to the study) that is expected to require indefinite, or lifelong, anticoagulation
5. Patient has an uncorrected bleeding disorder (platelet count &lt; 80,000/μL);
6. Patient has severe chronic renal insufficiency (serum creatinine level &gt; 2.5mg/dL) and not on hemodialysis;
7. Patient has a known hypercoagulability that cannot be corrected;
8. Patient has evidence of a blood borne infection;
9. Patient has had vascular access/catheterization in the lower extremity within 30 days of study enrollment;
10. Patient has had a previous or planned coronary intervention within 30 days prior to enrollment in this study or required at time of study procedure;

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11. Patient has had a previous or planned bypass surgery in the target leg, or a bypass that occurs at the time of the index procedure;
12. Patient is currently participating in this or another investigative clinical study.

## Angiographic Exclusion Criteria

1. Patient has a stent or stent graft located within or immediately adjacent (≤5mm) to study lesion(s);
2. Patient has evidence of angiographically visible thrombus within or adjacent to the target lesion(s);
3. Patient has aneurysmal dilation proximal or distal to the target lesion(s) that would interfere with the placement of the device;
4. Patient has a target lesion requiring atherectomy or any ablative device to facilitate stent delivery;
5. Patient has a target lesion situated in such a way that an implanted device will prevent blood flow or perfusion to the internal iliac artery if patent.

## 2. Follow-up Schedule

All patients were scheduled to return for follow-up examinations at 30 days (± 7 days), 9 months (± 30 days), 12 months (± 45 days), 24 months (± 45 days), and 36 months (± 45 days) postoperatively. The schedule of follow-up examinations is outlined in Table 5.

Table 5: Evaluations to be Completed at Each Study Interval

| Diagnostic Test / Collection Points | Pre-Procedure | Procedure | Discharge | Follow-up Interval | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | | 30 Days, 9 & 12 Months | 24 & 36 Months | Unscheduled Study Related Visit / Repeat Intervention |
| Informed Consent | X | | | | | |
| Inclusion / Exclusion | X | | | | | |
| Medical History & Demographic | X | | | | | |
| Antiplatelet / Anticoagulation Therapy | X | X | X | X | X | X |
| Blood Draws & β-hCG test, if applicable | X | | | | | |
| Rutherford Category | X | | | X | X | X |
| Resting ABI /TBI | X | | X | X | X | X |
| Iliac Artery Duplex Ultrasound & CFA Waveform, AT Measurement | | | X | X | If indicated | If indicated |
| Angiography | | X | | If indicated | If indicated | If indicated |
| EQ-5D | X | | | X | X | X |
| Walking Impairment Questionnaire | X | | | X | X | X |
| Assess Adverse Events | | X | X | X | X | X |

Common Femoral Artery (CFA), Acceleration Time (AT)

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## 3. Clinical Endpoints

With regards to safety and effectiveness, the primary endpoint of this study is a composite endpoint of Major Adverse Events (MAEs), defined as follows:

- Procedure- or device-related events causing death, occurring within 30 days of the index procedure; and
- Myocardial Infarction (MI) occurring within 30 days of the index procedure; and
- Target Lesion Revascularization (TLR) occurring within 9 months of the index procedure; and
- Major amputation of the treated leg(s), resulting from a vascular event, occurring within 9 months of the index procedure.

## Secondary Endpoints

The secondary endpoints in this study include:

- acute procedural success
- 30-day clinical success
- primary patency
- primary assisted patency
- secondary patency
- freedom from TLR (fTLR)
- freedom from clinically-driven TLR (fCD-TLR)
- freedom from target vessel revascularization (TVR) (fTVR)
- freedom from clinically-driven TVR (fCD-TVR)
- change in Rutherford category
- change in ankle-brachial index (ABI)
- change in functional status (based on subject questionnaires)

All of these secondary outcomes were evaluated descriptively without any pre-specified performance criteria.

## B. Patient Accountability of PMA Cohort

At the time of database lock, of 134 patients enrolled in the PMA study, 98.5% (132/134) patients were available for analysis at the completion of the study, the 9 month post-operative visit, as depicted in Table 6.

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Table 6: Subject Disposition through 9 months

| | 1 month visit (0-30 days) | 9 month visit (31-270) |
| --- | --- | --- |
| Number of Subjects Enrolled | 134 | 134 |
| Subjects completed the study | 0 (0.0%) | 0 (0.0%) |
| Subjects ongoing in study | 133 (99.2%) | 132 (98.5%) |
| Subjects discontinued the study | 1 (0.75%) | 1 (0.75%) |
| Withdrew consent | 0 (0.0%) | 0 (0.0%) |
| Investigator decision | 0 (0.0%) | 0 (0.0%) |
| Lost to follow-up | 1 (0.75%) | 0 (0.0%) |
| Death | 0 (0.0%) | 1 (0.75%) |
| Amputation above the femur | 0 (0.0%) | 0 (0.0%) |
| Surgical bypass of all study devices | 0 (0.0%) | 0 (0.0%) |
| Device used in subject but Not implanted | 0 (0.0%) | 0 (0.0%) |
| Other | 0 (0.0%) | 0 (0.0%) |

# C. Study Population Demographics and Baseline Parameters

Table 7 provides a summary of the baseline demographics and clinical characteristics of the study subjects.

Table 7: Baseline Demographics and Clinical Characteristics

| | N = 134 subjects |
| --- | --- |
| Gender at Birth | |
| Male | 79 (59.0%) |
| Age | |
| Mean (Std Dev) | 66 (9.5) |
| Race | |
| American Indian or Alaskan Native | 3 (2.2%) |
| Asian | 2 (1.5%) |
| Black or African American | 4 (3.0%) |
| Native Hawaiian or Pacific Islander | 0 (0.0%) |
| White | 123 (91.8%) |
| Other Race | 3 (2.2%) |
| Medical History and Risk Factors | |
| Smoking History | |
| Never smoked | 7 (5.2%) |
| Quit ≤ 1 year ago | 18 (13.4%) |
| Quit 1-5 years ago | 8 (6.0%) |
| Quit > 5 years ago | 43 (32.1%) |
| Current user | 58 (43.3%) |
| Diabetes | 38 (28.4%) |
| Hypertension | 113 (84.3%) |
| Hyperlipidemia | 104 (77.6%) |
| Hypercholesterolemia | 64 (47.8%) |
| Coronary Artery Disease | 56 (41.8%) |

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The baseline anatomic and lesion characteristics are reported in Table 8.

Table 8: Baseline anatomic and lesion characteristics

| By subject | |
| --- | --- |
| Access approach1 | N=134 |
| Ipsilateral | 27 (20.1%) |
| Contralateral | 24 (17.9%) |
| Bilateral | 83 (61.9%) |
| Treated Segments1 | N=134 |
| 1 | 59 (44.0%) |
| 2 | 71 (53.0%) |
| 3 | 4 (3.0%) |
| Treated Limb(s)1 | N=134 |
| Right | 29 (21.6%) |
| Left | 38 (28.4%) |
| Bilateral | 67 (50.0%) |
| Kissing Stent Procedure | 57 (42.5%) |
| Total Lesion Length per subject (mm)2 | N=132 |
| Mean (Std Dev) | 42.08 (23.98) |
| Total Stented Length per subject (mm)2 | N=133 |
| Mean (Std Dev) | 72.09 (29.39) |
| Number of devices per subject2 | N=134 |
| 1 | 51 (38.1%) |
| 2 | 69 (51.5%) |
| 3 | 12 (9.0%) |
| 4 | 1 (0.7%) |
| 5 | 1 (0.7%) |
| By limb | |
| Resting ABI1 | N=199 |
| Mean (Std Dev) | 0.77 (0.22) |
| Treated vessel(s)1 | N=201 |
| CIA (Common Iliac Artery) | 154 (76.6%) |
| EIA (External Iliac Artery) | 31 (15.4%) |
| CIA and EIA | 16 (8.0%) |
| Device(s) successfully delivered1 | N=201 |
| | 100.0% |

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| Max Post-procedure Residual Stenosis <= 30%1 | N=201
100.0% |
| --- | --- |
| By lesion | |
| Disease characterization2 | N=210 |
| Stenosis | 182 (86.7%) |
| Occlusion | 28 (13.3%) |
| Maximum Stenosis (%)2 | N=182 |
| Mean (Std Dev) | 62.1 (15.9) |
| Lesion Length (mm)2 | N=209 |
| Mean (Std Dev) | 26.6 (16.3) |
| Stented Length (mm)2 | N=212 |
| Mean (Std Dev) | 45.2 (14.4) |

1: site reported
2: core lab determination

## D. Safety and Effectiveness Results

### 1. Composite Primary Safety and Effectiveness Results

The primary endpoint result consisted of a composite of Major Adverse Events (Table 9). No device-or procedure related deaths and no myocardial infarctions for any subjects were reported within 30 days of the study procedure. No major amputations for any subjects were reported within 9 months of the study procedure. Target Lesion Revascularization (TLR) was reported for 3 subjects at days 186, 218 and 261. These events occurred within the 9 month follow-up interval and were adjudicated as primary endpoint events by the Clinical Events Committee. The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis demonstrated safety and effectiveness since the composite MAE of 2.3%, with the upper limit of the 95% confidence interval at 6.5%, was less than the performance goal of 17.0% (p&lt;0.001).

A sensitivity analysis was performed for testing the primary hypothesis in the intent-to-treat (ITT) population, which included all enrolled subjects, as well as the per-protocol (PP) population which included only those subjects who met the study inclusion criteria. The performance goal was met in both analyses with p-Values &lt;0.001, providing evidence for similarity of the results between the two populations. All endpoint data reported is based on the PP population, unless otherwise specified.

Table 9: Primary Endpoint

| Primary endpoint | Number (Fraction) [95% CI] |
| --- | --- |
| Subjects Available for Assessment | N=132 |
| Composite MAE | 3 (2.3%) [0.5%, 6.5%] |
| p-Value | <0.001 |
| Device or procedure related death within 30 days | 0 (0.0%) [0%, 2.3%] |
| MI within 30 days | 0 (0.0%) [0%, 2.3%] |
| TLR within 9 months | 3 (2.3%) [0.5%, 6.5%] |
| Major amputation within 9 months | 0 (0.0%) [0%, 2.3%] |

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# 2. Secondary Endpoints Results

Acute Procedural Success was defined as $\leq 30\%$ residual stenosis prior to procedure completion and no device- or procedure-related serious adverse events (SAEs) before discharge. Thirty-day Clinical Success was defined as an improvement of at least one Rutherford Category at the 30-day visit as compared to pre-procedure and no device- or procedure-related SAEs within 30 days of the index procedure. Primary patency was defined as blood flow in the treated segment(s), without reintervention. Acute procedural success was $97.0\%$ ( $N = 134$ subjects). Results of all other secondary endpoints at the predetermined follow-up are summarized in Table 10. Kaplan-Meier estimates of survival probability at 1 month and 9 months are shown for primary patency, primary assisted patency, secondary patency, freedom from TLR, freedom from clinically-driven TLR, freedom from TVR, and freedom from clinically-driven TVR.

Upon completion angiography, there were no instances of residual stenosis greater than $30\%$ (Table 8). Four subjects experienced 5 SAEs before discharge, resulting in a $97.0\%$ acute procedural success rate. One subject did not show evidence of blood flow through the treated segment at 1 month follow-up yet no treatment was attempted, therefore resulting in $99.2\%$ primary patency, primary assisted patency, and secondary patency at 30 days but $100\%$ freedom from TLR at 30 days.

Change in functional status from pre-procedure: At 9 months vs. baseline, median walking distance, walking speed, and stair climbing scores improved at least four-fold. Eighty five percent of subjects reported an improvement or maintenance of quality of life measures (EQ-5D) at 9 months compared to pre-procedure.

Table 10: Secondary Endpoints, by subject ${}^{1}$

| Endpoint | 1 month | 9 months |
| --- | --- | --- |
| 30-day clinical success | 90.8% (N=119) | NA |
| Primary Patency | 99.2% (N=128) | 96.7% (N=98) |
| Primary Assisted Patency | 99.2% (N=128) | 99.2% (N=101) |
| Secondary Patency | 99.2% (N=128) | 99.2% (N=101) |
| fTLR | 100.0% (N=133) | 97.7% (N=109) |
| fCD-TLR | 100.0% (N=133) | 98.4% (N=110) |
| fTVR | 100.0% (N=133) | 97.7% (N=109) |
| fCD-TVR | 100.0% (N=133) | 97.7% (N=109) |
| Change in Rutherford from pre-procedure | worsened/maintained/improved 0.8% / 5.1% / 94.1% (N=118) | worsened/maintained/improved 0.0% / 5.4% / 94.6% (N=112) |
| Change in ABI from pre-procedure1 Mean (Std Dev) | 0.19 (0.22) (N=172) | 0.19 (0.22) (N=168) |
| Change in functional status from pre-procedure | | |
| EQ-5D | worsened/maintained/improved 6.1% / 49.6% / 44.3% (N=115) | worsened/maintained/improved 3.5% / 54.4% / 42.1% (N=114) |
| Mobility | 1.7% / 93.9% / 4.3% (N=115) | 2.6% / 92.1% / 5.3% (N=114) |
| Self-Care | 7.0% / 47.8% / 45.2% (N=115) | 3.5% / 50.0% / 46.5% (N=114) |
| Usual Activities | 8.7% / 42.6% / 48.7% (N=115) | 8.8% / 48.2% / 43.0% (N=114) |
| Pain/Discomfort | | |

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| Anxiety/Depression | 5.2% / 71.3% / 23.5% (N=115) | 6.1% / 69.3% / 24.6% (N=114) |
| --- | --- | --- |
| Own Health State (1-100) | 7.0% / 73.7% / 19.3% (N=114) | 15.0% / 64.6% / 20.4% (N=113) |
| WIQ² (Walking Impairment Questionnaire) | Median (IQR) | Median (IQR) |
| Differential Diagnosis | 2 (0, 4) (N=115) | 1 (0, 4) (N=114) |
| Walking Distance | 10 (3, 19) (N=115) | 10 (3, 18) (N=114) |
| Walking Speed | 5 (1, 8) (N=114) | 5 (0, 9) (N=114) |
| Stair Climbing | 4 (1, 8) (N=107) | 4 (0, 7) (N=110) |

¹ ABI reported on per-limb basis
² Higher scores indicate a healthier state

# 3. Additional Results

Since a significant fraction of the overall population received kissing stents (42.5%, Table 8), additional analysis of the composite primary endpoint was conducted for this subgroup (Table 11).

Table 11: Primary endpoint for the kissing stent subgroup

| Primary endpoint – kissing stent subgroup | Number (Fraction) [95% CI] |
| --- | --- |
| Subjects Available for Assessment | N=57 |
| Composite MAE | 2 (3.5%) [0.4%, 12.1%] |
| Device or procedure related death within 30 days | 0 (0.0%) [0%, 5.3%] |
| MI within 30 days | 0 (0.0%) [0%, 5.3%] |
| TLR within 9 months | 2 (3.5%) [0.4%, 12.1%] |
| Major amputation within 9 months | 0 (0.0%) [0%, 5.3%] |

# 4. Summary of Serious Adverse Events that Occurred in the VBX FLEX Clinical Study

A description of all adjudicated/unrefuted SAEs through 9 months is provided in Table 12. Two (2) patients were censored from the primary endpoint analysis. The reasons for discontinuation (missing data) were lost to follow-up and death. This death occurred on Day 187 and was not associated with the study device or procedure. This death was related to subject co-morbidities that resulted in cardiac arrest. No subjects experienced a SAE related to the study device within 9 months. There were no unanticipated device-related events reported in the study within 9 months.

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Table 12: Description of Serious Adverse Events through 9 months

| Subjects Enrolled | 134 |
| --- | --- |
| Subjects Experiencing Serious Adverse Events | 30 (22.4%) [43] |
| | |
| Blood and lymphatic system disorders | 1 (0.7%) [1] |
| Haemorrhagic anaemia | 1 (0.7%) [1] |
| Cardiac disorders | 4 (3.0%) [4] |
| Acute myocardial infarction | 1 (0.7%) [1] |
| Angina pectoris | 1 (0.7%) [1] |
| Cardiac failure congestive | 1 (0.7%) [1] |
| Coronary artery disease | 1 (0.7%) [1] |
| Gastrointestinal disorders | 3 (2.2%) [3] |
| Gastrointestinal haemorrhage | 1 (0.7%) [1] |
| Rectal haemorrhage | 1 (0.7%) [1] |
| Umbilical hernia | 1 (0.7%) [1] |
| General disorders and administration site conditions | 2 (1.5%) [2] |
| Non-cardiac chest pain | 1 (0.7%) [1] |
| Vascular stent occlusion | 1 (0.7%) [1] |
| Infections and infestations | 4 (3.0%) [4] |
| Clostridium difficile infection | 1 (0.7%) [1] |
| Pneumonia | 1 (0.7%) [1] |
| Postoperative wound infection | 1 (0.7%) [1] |
| Urinary tract infection | 1 (0.7%) [1] |
| Injury, poisoning and procedural complications | 8 (6.0%) [10] |
| Arterial restenosis | 1 (0.7%) [1] |
| Humerus fracture | 1 (0.7%) [1] |
| Incisional hernia | 1 (0.7%) [1] |
| Joint dislocation | 1 (0.7%) [1] |
| Post procedural haematoma | 1 (0.7%) [1] |
| Postoperative ileus | 1 (0.7%) [1] |
| Vascular pseudoaneurysm | 2 (1.5%) [2] |
| Wound dehiscence | 2 (1.5%) [2] |
| Metabolism and nutrition disorders | 1 (0.7%) [1] |
| Hyperkalaemia | 1 (0.7%) [1] |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 (1.5%) [2] |
| Lung adenocarcinoma | 1 (0.7%) [1] |
| Prostate cancer | 1 (0.7%) [1] |
| Nervous system disorders | 2 (1.5%) [2] |
| Carotid artery stenosis | 1 (0.7%) [1] |
| Vascular dementia | 1 (0.7%) [1] |

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| Renal and urinary disorders | 1 ( 0.7%) [1] |
| --- | --- |
| Acute kidney injury | 1 ( 0.7%) [1] |
| Respiratory, thoracic and mediastinal disorders | 1 ( 0.7%) [1] |
| Chronic obstructive pulmonary disease | 1 ( 0.7%) [1] |
| Vascular disorders | 8 ( 6.0%) [11] |
| Femoral artery dissection | 1 ( 0.7%) [1] |
| Haematoma | 1 ( 0.7%) [1] |
| Hypovolaemic shock | 1 ( 0.7%) [1] |
| Intermittent claudication | 2 ( 1.5%) [3] |
| Lymphocele | 1 ( 0.7%) [1] |
| Peripheral arterial occlusive disease | 1 ( 0.7%) [1] |
| Peripheral artery stenosis | 1 ( 0.7%) [1] |
| Peripheral ischaemia | 1 ( 0.7%) [1] |
| Poor peripheral circulation | 1 ( 0.7%) [1] |

## 5. Subgroup Analysis

### Applicability to Pediatric Population

Peripheral artery disease is not typically found in pediatric populations. The GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is not indicated for use in pediatric patients. The VBX FLEX clinical study did not evaluate safety and effectiveness in the pediatric population.

### VBX FLEX Study Results by Gender

Gender analysis was performed for the study primary endpoint. The heterogeneity of the primary endpoints between gender (male and female) was tested with a Fisher's Exact Test. An unadjusted p-value of 0.05 or less was considered evidence of a possible gender difference. The comparison of the primary endpoint MAE between genders was not significant (p = 0.066, Fisher's Exact Test, 2-sided).

## E. Financial Disclosure

The Financial Disclosure by Clinical Investigators regulation (21 CFR 54) requires applicants who submit a marketing application to include certain information concerning the compensation to, and financial interests and arrangement of, any clinical investigator conducting clinical studies covered by the regulation. The VBX FLEX clinical study included five investigators who had disclosable financial interests/arrangements as defined in 21 CFR 54.2(a), (b), (c) and (f) and described below:

- Compensation to the investigator for conducting the study where the value could be influenced by the outcome of the study: None
- Significant payment of other sorts: five investigators

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- Proprietary interest in the product tested held by the investigator: None
- Significant equity interest held by investigator in sponsor of covered study: None

The applicant has adequately disclosed the financial interest/arrangements with clinical investigators. The information provided does not raise any questions about the reliability of the data.

## XI. PANEL MEETING RECOMMENDATION AND FDA'S POST-PANEL ACTION

In accordance with the provisions of section 515(c)(2) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the Circulatory System Devices Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel.

## XII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES

### A. Safety and Effectiveness Conclusions

In vitro bench testing, sterilization, packaging, product shelf life, animal, and biocompatibility testing, along with the clinical studies discussed above, provided reasonable assurance that the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is safe and acceptable for clinical use, in accordance with regulatory and industry standards and guidance documents. The VBX FLEX prospective, multicenter clinical study demonstrated safety and effectiveness of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis since the composite MAE of 2.3%, with the upper limit of the 95% confidence interval at 6.5%, was less than the performance goal of 17.0% (p&lt;0.001). This performance goal was established based on previous iliac stenting study outcomes. Similar iliac stenting studies reported composite MAEs ranging from 0-15% at 9 months.

TLR comprised all observed MAEs in the composite primary endpoint, with the other 3 components being 0%. Within 9 months, no subjects experienced a SAE related to the study device and there were no unanticipated device-related events reported. In addition, the observed improvements in Rutherford Category and functional status (WIQ and EQ-5D) at 9 months demonstrate that the study device can be safely implanted to restore blood flow and provides improvement of clinical symptoms. Overall, the results of this study support the safety and effectiveness of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis for the treatment of arterial occlusive iliac disease in the studied patient population.

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## B. Benefit/Risk Conclusions

The primary potential benefit of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is the improvement or restoration of blood flow in the iliac arteries. The patients enrolled in this study were symptomatic, ranging from moderate quality of life-limiting claudicants to patients with resting leg pain. In the study, the patients demonstrated improvement in functional status and Rutherford Category when compared to pre-procedure assessments. Also, the low incidence of repeat procedures to treat recurrent disease in the study device through 9 months demonstrates clinical benefit (TLR of 2.3%).

The risks associated with balloon-expandable stents are well-understood, and the frequency and types of adverse events reported throughout the pivotal clinical study are in alignment with expectations for the studied patient population and therapeutic area. By 9 months, no patients experienced a device- or procedure-related SAE or unanticipated adverse event

Give the available information from the non-clinical, pre-clinical, and clinical studies, the data support that the probable benefits outweigh the probably risks for using the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis for the treatment of de novo or restenotic lesions found in iliac arteries with reference vessel diameters ranging from 5mm - 13mm and lesion lengths up to 110mm, including lesions at the aortic bifurcation.

## 1. Patient Perspectives

Patient perspectives considered during the review included Quality of Life assessments, specifically WIQ and EQ-5D. Scores for treated patients improved based on pre-procedure assessments. It is expected that patients would place value on this treatment, are willing to take the risks of this treatment to achieve the benefit, and would be able to understand the benefits and risks of treatment with the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis without difficulty.

## C. Overall Conclusions

The clinical and non-clinical data generated with the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis is safe and effective. The clinical study met the pre-specified composite safety and effectiveness endpoint. Therefore, it is reasonable to conclude that the benefits of the use of the device for the target population outweigh the risk of illness or injury when used as indicated in accordance with the labeling and Instructions for Use (IFU).

## XIII. CDRH DECISION

CDRH issued an approval order on 1/27/2017. The final conditions of approval cited in the approval order are described below.

ODE Lead PMA Post-Approval Study– VBX FLEX Continued Follow-Up Study:

The Office of Device Evaluation (ODE) will have the lead for this clinical study, which was initiated prior to device approval. This study must be conducted per protocol BES 10-07 (dated

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February 19, 2014) and the Post-Approval Study Analysis Plan (also dated February 19, 2014). This study is a prospective, randomized, multi-center follow-up of the BES 10-07 pivotal study (G120232). It will evaluate the long term safety and effectiveness of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis. All 133 remaining subjects (7 subjects have discontinued the study) of the 140 original study subjects enrolled in the BES 10-07 study from 27 investigational sites will continue to be followed annually through 36 months. The primary endpoint to be assessed is freedom from target lesion revascularization at 36 months, as defined by the protocol. The secondary endpoints to be assessed include the following:

- Freedom from target vessel revascularization (TVR) at 12, 24 and 36 months.
- Freedom from target lesion revascularization (TLR) at 12 and 24 months.
- Primary patency at 12 months.
- Primary assisted patency at 12 months.
- Secondary patency at 12 months.
- Change in Rutherford category from pre-procedure at 12, 24 and 36 months.
- Change in resting Ankle-Brachial Index (ABI) or Toe Brachial Index (TBI) from pre-procedure at 12, 24 and 36 months.
- Change in functional status from pre-procedure based on EQ-5D at 12, 24 and 36 months.
- Change in functional status from pre-procedure based on Walking Impairment Questionnaire (WIQ) at 12, 24 and 36 months.
- Serious adverse events at 12, 24 and 36 months

The applicant’s manufacturing facility(ies) has/have been inspected and found to be in compliance with the device Quality System (QS) regulation (21 CFR 820).

## XIV. APPROVAL SPECIFICATIONS

Directions for use: See device labeling.

Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, Precautions, and Adverse Events in the device labeling.

Post-approval Requirements and Restrictions: See approval order.

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