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

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

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).

Study Overview

• Status: Completed
• Conditions: Peripheral Artery Disease
• Intervention / Treatment: Biological: PVS-10200

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • Centre Hospitalier Universitaire d'Amiens
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75018
    • Hôpital Bichat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject has signed the informed consent document and patient information leaflet.
2. Male and female subject ≥ 18 years of age at the time of consent.
3. 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).
4. Subject has symptomatic peripheral arterial disease involving the superficial femoral artery, defined as Fontaine Class IIb, III and IV.

5. 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
6. Target lesion is 7-15 cm in length.
7. Subject is expected to stay in the same geographic area for at least 48 weeks.
8. In the opinion of the investigator, the subject is able to understand and is willing to complete the study requirements.
9. 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:

1. Subject has acute limb ischemia.
2. Subject has had prior revascularization of the target lesion.
3. Subject has untreated inflow disease of the ipsilateral pelvic arteries (> 50% stenosis or occlusion).
4. 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).
5. Subject has an unresolved thrombus within the target vessel.
6. Additional percutaneous interventional procedures (cardiac/peripheral) are planned ≤ 30 days following the study procedure.
7. Subject has suffered a hemorrhagic stroke ≤ 6 mo prior to the study procedure.
8. Subject has a history of bleeding diatheses or coagulopathy.
9. Subject is diagnosed with septicemia at the time of the study procedure.
10. Subject is known to be seropositive for HIV.
11. Subject has some other medical illness that may cause the subject to be non-compliant with the protocol.
12. Subject has a known allergy to bovine or porcine products (i.e., heparin).
13. Subject has a known allergy to collagen/gelatin products.
14. Subject has had a severe reaction to contrast media.
15. Subject has a known allergy or intolerance to anti-platelet medication (e.g., acetylsalicylic acid or clopidogrel) or statin therapy.
16. Subject has a history of IV drug use within 6 months prior to screening.
17. Subject has a documented diagnosis of cancer within 2 years (24 months) prior to screening.
18. Subject is a female who is pregnant, breast-feeding, or plans to become pregnant during the study.
19. 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.
20. Subject is a staff member of any of the participating institutions or relative of a staff member.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: PVS-10200; 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; PVS-10200 is composed of allogeneic human aortic endothelial cells cultured in a gelatin matrix.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Sevestre MA, Larghero J, Castier Y, Nugent HM, Visonneau S, Alsac JM. Pilot safety study of perivascular injection of tissue-engineered allogeneic aortic endothelial cells in patients undergoing minimally invasive peripheral revascularization. J Vasc Surg. 2014 Jun;59(6):1597-606. doi: 10.1016/j.jvs.2014.01.014. Epub 2014 Mar 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 30, 2010
• Primary Completion (ACTUAL): June 30, 2012
• Study Completion (ACTUAL): October 31, 2012

Study Registration Dates

• First Submitted: April 1, 2010
• First Submitted That Met QC Criteria: April 5, 2010
• First Posted (ESTIMATE): April 6, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 28, 2021
• Last Update Submitted That Met QC Criteria: June 4, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: stent; peripheral artery disease; percutaneous transluminal angioplasty; superficial femoral artery; balloon/stent
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease
• Other Study ID Numbers: PVS 03-001; 2009-011998-32 (EUDRACT_NUMBER)