Study of PVS-10200 for the Treatment of Restenosis in Patients With Peripheral Artery Disease (TRIUMPH)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of two doses of PVS-10200, an allogeneic cellular therapy, delivered as a single injection following percutaneous transluminal (balloon) angioplasty and stent placement for the treatment of peripheral artery disease (PAD).

Detailed Description
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This is an open-label dose escalation safety study of PVS-10200 in 30 subjects with peripheral artery disease (PAD) requiring balloon angioplasty and stent placement in the superficial femoral artery (SFA). The study will be completed sequentially in two dose cohorts of 10 subjects (low dose group, Cohort A) and 20 subjects (high dose group, Cohort B). A Data Safety Monitoring Board (DSMB) will conduct regular safety reviews. Each subject will receive one treatment of PVS-10200 delivered by ultrasound guided injection to the perivascular region (external to the vessel) of the stented target lesion. The treatment will be administered within 24 hours after balloon angioplasty/stent placement.

Official Title
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An Open-Label Dose Escalation Safety Study of PVS-10200 for the Treatment of Restenosis in Patients Undergoing Minimally Invasive Peripheral Revascularization (TRIUMPH)

Conditions
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Peripheral Artery Disease

Intervention / Treatment
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* Biological: PVS-10200


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has signed the informed consent document and patient information leaflet. Male and female subject ≥ 18 years of age at the time of consent. If female, the subject is (a) at least 1 year post-menopausal, or (b) surgically sterile, or (c) of child-bearing potential, with a negative serum pregnancy test result prior to study enrollment, who agrees to use adequate contraception for 6 months. Adequate contraception is defined as abstinence or a reliable method of birth control (e.g., a hormonal contraceptive, intra-uterine device, implantable or injectable contraceptives (Norplant® or Depo-Provera®), diaphragm, or condom with spermicide). Subject has symptomatic peripheral arterial disease involving the superficial femoral artery, defined as Fontaine Class IIb, III and IV. Meets anatomic requirements based on biplane digital subtraction angiography performed at the time of intervention including: Stenosis of ≥ 50% or occlusion of the superficial femoral artery, and Target lesion length of ≤ 150 mm, and At least one patent (< 50 % stenosis) tibioperoneal runoff vessel Target lesion is 7-15 cm in length. Subject is expected to stay in the same geographic area for at least 48 weeks. In the opinion of the investigator, the subject is able to understand and is willing to complete the study requirements. Subject is receiving a therapeutic dose of statin therapy (starting minimum of 7 days prior to intervention) and continuing for a minimum of 4 weeks post-intervention. Exclusion Criteria: Subject has acute limb ischemia. Subject has had prior revascularization of the target lesion. Subject has untreated inflow disease of the ipsilateral pelvic arteries (> 50% stenosis or occlusion). The target lesion is located within an aneurysm or associated with an aneurysm in the vessel segment either proximal or distal to the target lesion(s). Subject has an unresolved thrombus within the target vessel. Additional percutaneous interventional procedures (cardiac/peripheral) are planned ≤ 30 days following the study procedure. Subject has suffered a hemorrhagic stroke ≤ 6 mo prior to the study procedure. Subject has a history of bleeding diatheses or coagulopathy. Subject is diagnosed with septicemia at the time of the study procedure. Subject is known to be seropositive for HIV. Subject has some other medical illness that may cause the subject to be non-compliant with the protocol. Subject has a known allergy to bovine or porcine products (i.e., heparin). Subject has a known allergy to collagen/gelatin products. Subject has had a severe reaction to contrast media. Subject has a known allergy or intolerance to anti-platelet medication (e.g., acetylsalicylic acid or clopidogrel) or statin therapy. Subject has a history of IV drug use within 6 months prior to screening. Subject has a documented diagnosis of cancer within 2 years (24 months) prior to screening. Subject is a female who is pregnant, breast-feeding, or plans to become pregnant during the study. Subject is currently participating in another investigational drug, biologic or device trial, plans to participate in another investigational drug, biologic or device study during participation in this study, or has completed participation in another investigational drug, biologic or device trial within the last 30 days. Note: Subjects involved in extended follow-up trials for products that are currently commercially available and used as approved are not considered to be participating investigational trials. Subject is a staff member of any of the participating institutions or relative of a staff member.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: PVS-10200<br>Each subject will receive one treatment of PVS-10200 delivered by ultrasound guided injection perivascular to the region of the target lesion within 24 hours of the completed angioplasty and stent placement. | Biological: PVS-10200<br>* PVS-10200 is composed of allogeneic human aortic endothelial cells cultured in a gelatin matrix.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Major Adverse Events (MAEs) | Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events | within 4 weeks after study procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Major Adverse Events (MAEs) | Major Adverse Events are: - Death - Major amputation - Procedural related serious adverse events - Investigational product related serious adverse events | within 24 and 48 weeks from study procedure | 
| Incidence of Serious Adverse Events |  | Up to 48 weeks from study procedure | 
| Incidence of Adverse Events, Laboratory Abnormalities |  | Up to 48 weeks from study procedure | 
| Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 4 weeks from study procedure | 
| Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 24 weeks from study procedure | 
| Maintenance of Primary Patency of Superficial Femoral Artery (SFA) | Primary patency was defined as duplex ultrasound peak systolic velocity [PSV] ratio ≤2.4.Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 48 weeks from study procedure | 
| Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 4 weeks from study procedure | 
| Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 24 weeks from study procedure | 
| Rate of Binary In-stent Restenosis | Binary restenosis relied on duplex ultrasound data with a Yes/No assessment with 0-49% being No (peak systolic velocity [PSV] ratio ≤2.4) and Yes being 50-99% (PSV ratio >2.4), with the PSV ratio calculated as PSV from stenosis divided by the PSV from a normal segment of artery proximal to the stenosis. Ultrasound data was obtained for each patient at each time point and had to be considered diagnostic and evaluable by the core lab; if it was not, then this analysis could not be done for that particular subject. | within 48 weeks from study procedure | 
| Number of Patients Requiring Reintervention of Target Lesion / Target Vessel | Survival analysis - outcome reported as patients requiring reintervention of the target lesion / vessel | up to 48 Weeks from study procedure | 
| Resting Ankle-brachial Index | ABI was calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressures in the arm. This test is used to predict the severity of PAD. | within 4, 24 and 48 weeks from study procedure | 
| Changes in Physical Exam | Changes in physical examination were compared to baseline: numbers of subjects presenting any new finding or worsening of abnormal findings compared to the screening examination are reported | within 4, 24 and 48 weeks from baseline | 
| The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | change from baseline to 4 weeks | 
| The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | change from baseline to 24 weeks | 
| The Fontaine Class of Peripheral Artery Disease | CLASSIFICATION OF PERIPHERAL ATERIAL DISEASE ACCORDING TO FONTAINE Stage Clinical description I Asymptomatic IIA Mild claudication IIB Moderate -severe claudication III Ischemic rest pain IV Ulceration or gangrene | change from baseline to 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral artery disease, percutaneous transluminal angioplasty, stent, balloon/stent, superficial femoral artery