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Safety and Efficacy Study of Ad2/Hypoxia Inducible Factor (HIF)-1α/VP16 Gene Transfer in Patients With Intermittent Claudication | Clinical Trials | Clareo Health

COMPLETEDPHASE2

Safety and Efficacy Study of Ad2/Hypoxia Inducible Factor (HIF)-1α/VP16 Gene Transfer in Patients With Intermittent Claudication

A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Dose-Selection Study of Ad2/Hypoxia Inducible Factor (HIF)-1α/VP16 in Patients With Intermittent Claudication

NCT00117650•Genzyme, a Sanofi Company

View on ClinicalTrials.gov

Summary

The purpose of this Phase 2 clinical research study is to examine the safety of an experimental gene transfer agent, Ad2/HIF-1α/VP16, and its ability to stimulate the growth of new blood vessels from existing blood vessels (a process called angiogenesis) in an attempt to improve the flow of blood in the legs of patients with peripheral arterial disease (PAD). Specifically, this study will enroll patients with severe intermittent claudication (IC) which is the stage of PAD in which a patient's walking ability is severely limited, causing pain in the legs upon exercise due to inadequate blood flow to the muscles of the lower limbs.

Detailed Description

This Phase 2 gene transfer study will look at whether different doses of Ad2/HIF-1α/VP16 can be tolerated safely by direct injection into the leg muscles where the blood flow is not sufficient to meet the oxygen demands of the leg muscles. The study will also assess whether patients who receive the investigational drug product are able to increase their maximal walking time using a standardized treadmill walking test. The study design is a randomized, double-blind, placebo-controlled, parallel group, multi-center, Phase 2 dose-selection study. Seventy-five patients will be enrolled into each of 4 study drug groups (3 groups of Ad2/HIF-1α/VP16 gene transfer and 1 placebo group) for a total of 300 patients overall. Three different doses of Ad2/HIF-1α/VP16 gene transfer will be studied. The dose range was previously tested in animals and in the Phase 1 human studies. A placebo group is included in the study to compare safety and efficacy of different doses of Ad2/HIF-1α/VP16 with placebo. Each patient will receive a single set of 20 injections (100 μL each) of gene transfer or placebo in one administration to each leg for a total of 40 injections.

Eligibility

Age

40 - 80 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Males and females 40 to 80 years of age, inclusive.
•Clinical diagnosis of PAD, secondary to atherosclerosis, in both lower limbs, confirmed by objective evidence: An ankle-brachial index (ABI) of ≤ 0.90 at rest in at least 1 lower limb (Note: The index limb must be ≤ 0.90 at rest.); The ABI after exercise must be reduced by ≥ 20% from the ABI at rest in the index leg (the most symptomatic leg during the treadmill testing). The post-exercise ABI will also be performed on the other leg if the resting ABI \> 0.90. A patient may be eligible for the study with a resting ABI in the non-index limb \> 0.90 if: a. The post-exercise ABI in the non-index leg is also reduced by greater than or equal to 20% OR; b. A medically significant stenosis (defined as ≥ 50%) of a femoropopliteal or infrapopliteal artery is present, as documented via an imaging study (such as MR, conventional angiography, duplex ultrasound, or CT); If the ABI cannot be measured in either leg (due to non-compressible arteries), then a toe-brachial index (TBI) of ≤ 0.70 may be used in its place to confirm PAD.
•Symptoms of severe intermittent claudication (IC) in at least 1 lower limb persisting for ≥ 6 months
•Patients with a peak walking time (PWT) of 1 to 12 minutes (inclusive) using the standardized exercise treadmill test at each of the 2 consecutive treadmill tests performed at least a week apart during the Screening period.
•During Screening, patients must demonstrate consistency of PWTs between 2 standardized exercise treadmill tests (Walk 1 and Walk 2) performed at least 1 week apart.
•Consistency of the PWT between the 2 visits is achieved if the difference between PWT at Walk 1 and Walk 2 is ≤ 25% of the higher of the 2 PWTs (\[higher PWT - lower PWT\]/higher PWT).
•If the difference between PWT at Walk 1 and Walk 2 is \> 25% of the higher of the 2 PWTs, a third treadmill test (Walk 3) may be performed at the discretion of the Principal Investigator between 7 and 14 days following Walk 2. The variability in PWT warranting the performance of Walk 3 must be secondary to circumstances that may contribute to the observed variation (e.g., prior exertion, inconsistent timing, ingestion of a meal within 4 hours, etc). To qualify for the study, the difference between PWT of either Walk 1 or Walk 2 as compared with Walk 3 must be ≤ 25% of the higher of the 2 PWTs (\[higher PWT - lower PWT\]/higher PWT). The decision whether Walk 1 or Walk 2 will be used for comparison with Walk 3 will be made prospectively and reviewed with the Sponsor.
•An acceptable mean PWT must be achieved within 4 weeks of treatment administration.
•Patients have been considered for other potential treatment options including exercise rehabilitation, smoking cessation, and pharmacological therapy prior to Enrollment.
•Claudication severity, concomitant medications for the treatment of CAD, PAD, and IC, smoking status and exercise habits should be clinically stable for 3 months prior to Enrollment.
+1 more criteria

Exclusion Criteria

•Patients with either current or any history of Critical Limb Ischemia (CLI; that is, patients classified as Rutherford Category 4 \[ischemic rest pain\], Rutherford Category 5 \[non-healing ischemic ulcers and minor tissue loss\], or Rutherford Category 6 \[non-healing ischemic ulcers and major tissue loss\]).
•Patients in whom arterial insufficiency in the lower extremity is the result of acute limb ischemia or an immunological or inflammatory non-atherosclerotic disorder (eg, thromboangiitis obliterans \[Buerger's Disease\]) and systemic sclerosis \[both limited and diffuse forms\]).
•A PAD-specific surgical revascularization procedure within 6 months of enrollment or a PAD-specific percutaneous procedure within 3 months of enrollment, or patients likely to require a PAD-specific revascularization procedure within 6 months after Enrollment.
•Patients with aortoiliac disease that limits inflow in either leg: a. Patients with concomitant aortoiliac disease (i.e., patients with a significant component of inflow disease in the distal aorta, common or external iliac, or proximal common femoral artery) as assessed by an imaging modality (e.g., segmental limb pressures and waveform analysis, duplex ultrasound scanning, magnetic resonance angiography, or radio-contrast arteriogram) performed within 1 year prior to Enrollment. If subject has had a bypass after the imaging study, then documentation of graft patency is required within 6 months prior to Enrollment; b. If it is suspected at Screening that a patient has aortoiliac disease based on vascular examination, an imaging modality (e.g., segmental limb pressures and waveform analysis, duplex ultrasound scanning, magnetic resonance angiography, or radio-contrast arteriogram) must be performed to rule it out if there is not one available within the times specified above. If there is no suspicion of aortoiliac disease in the Principal Investigator's judgment, an imaging test at Screening is not required for study purposes.
•Patients in whom walking impairment due to pain in the index leg is the result of these nonatherosclerotic comorbid conditions: venous claudication, chronic compartment syndrome, peripheral nerve pain (e.g., severe peripheral neuropathy), pseudoclaudication caused by spinal cord compression, or acute limb ischemia which, in the Principal Investigator's judgment are severe enough to confound the assessment of the patient's IC.
•Conditions other than IC of significant severity that could confound PWT on the standardized exercise treadmill test causing premature or inconsistent termination of exercise (e.g., angina pectoris, heart failure \[New York Heart Association {NYHA} Classes III and IV\], respiratory disease \[e.g., chronic obstructive pulmonary disease\], orthopedic disease, neurological disorders, rheumatologic disorders \[e.g., severe degenerative joint diseases\], dyspnea, fatigue, prior lower limb amputation, including amputations proximal to the metatarsal or phalangeal joints).
•Presence or history of cancer within 5 years of enrollment or not current with recommended screening guidelines for colorectal, lung, prostate, breast, cervical, and uterine cancers, with the exception of low grade and fully resolved non-melanoma skin malignancy.
•Patients with a well-defined clinical or genetic disorder predisposing to malignancy should be excluded (e.g., von Hippel Lindau, familial polyposis coli, BRCA1, BRCA2, etc).
•Patients with baseline funduscopic evidence of active proliferative diabetic retinopathy, preproliferative diabetic retinopathy, or wet AMD AND/OR Patients with a history of treatment for active proliferative diabetic retinopathy or wet AMD within 5 years of enrollment.
•Diabetes type 1 (juvenile onset)
+11 more criteria

Locations (47)

Baptist Medical Center Princeton

Birmingham, Alabama, United States

VA Palo Alto Health Care System

Palo Alto, California, United States

University of California at Davis

Sacramento, California, United States

Stanford University School of Medicine

Stanford, California, United States

University of Colorado Health Sciences Center

Denver, Colorado, United States

The Washington Hospital Center

Washington D.C., District of Columbia, United States

Palm Beach Heart Institute

Atlantis, Florida, United States

Baptist Health Care

Pensacola, Florida, United States

University of South Florida

Tampa, Florida, United States

Saint Joseph's Research Institute

Atlanta, Georgia, United States

Key Dates

Start Date

February 1, 2005

Primary Completion Date

September 1, 2008

Completion Date

March 1, 2010

Last Updated

April 3, 2015

Enrollment

289

ACTUAL participants

Conditions

Intermittent ClaudicationPeripheral Vascular DiseaseAtherosclerosis

Interventions

Ad2/HIF-1α/VP16

BIOLOGICAL

Ad2/HIF-1α/VP16

BIOLOGICAL

Ad2/HIF-1α/VP16

BIOLOGICAL

Saline (Placebo Control)

OTHER

Characterization of Patients With Uncommon Presentations and/or Uncommon Diseases Associated With the Cardiovascular System

NCT01143454

Metabolic DiseaseObesity+4 more

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Atherosclerosis Cardiovascular DiseaseChronic Kidney Disease

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: April 3, 2015Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Safety and Efficacy Study of Ad2/Hypoxia Inducible Factor (HIF)-1α/VP16 Gene Transfer in Patients With Intermittent Claudication

Inclusion Criteria

Exclusion Criteria

Characterization of Patients With Uncommon Presentations and/or Uncommon Diseases Associated With the Cardiovascular System

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