Peripheral Arterial Disease (PAD): Intermittent Claudication (IC) MedDRA version: 9.1 Level: LLT Classification code 10009241 Term: Claudication intermittent
Conditions
Interventions
Product Name: Ad2/HIF-1a/VP16
Product Code: Ad2/HIF-1a/VP16
Pharmaceutical Form: Solution for injection
Current Sponsor code: Ad2/ HIF-1a/VP16
Concentration unit: ml millilitre(s)
Concentration numb
Sponsors
Genzyme Europe BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male and females 40 to 80 years of age, inclusive. 2.Clinical diagnosis of peripheral arterial disease (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. •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 -the post-exercise ABI in the non-index limb is also reduced by greater than or equal to 20% (according to current protocol)or -a medically significant stenosis of a femeropopilteal or infrapopliteal artery is present, as documented via imaging study (such as MR, conventional angiography, duplex ultrasound, or CT) •If the ABI cannot be measured in either leg (due to noncompressable arteries), then a toe-brachial index (TBI) of = 0.70 may be used in its place to confirm PAD. 3.Symptoms of severe IC in at least 1 lower limb persisting for = 6 months. 4.Patients with a PWT of 1 to 12 minutes (inclusive) using the standard 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 (eg, 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 3 weeks of treatment administration. 5.Patients have been considered for other potential treatment options including exercise rehabilitation, smoking cessation, and pharmacological therapy prior to enrollment. 6.Claudication severity, concomitant medications for the treatment of coronary artery disease (CAD), PAD, and IC, smoking status and exercise habits should be clinically stable for 3 months prior to Screening. 7.At Screening, patients will be required to be in compliance with the American Cancer Society (ACS) or other current national recommended guidelines for screening for malignancies of the colon, lung, breast, cervix, uterus (females only) and prostate (males only). 8.Patients who are committed to following the protocol requirements as evidenced by written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=6
Exclusion criteria
Exclusion criteria: 1.Patients with either current or any history of critical limb ischemia (CLI) (classified as Rutherford Category 4,5 or 6). 2.Patients in whom arterial insufficiency in the lower extremity is the result of acute limb ischemia or an immunological or inflammatory non-atherosclerotic disorder and systemic sclerosis. 3.A PAD-specific surgical revascularization procedure within 6 months of Enrollment or PAD-specific a percutaneous procedure within 3 months of Enrollment, or patients likely to require a PAD-specific revascularization procedure within 6 months after Enrollment. 4.Patients with aortoiliac disease that limits inflow in either leg. 5.Patients in whom walking impairment due to pain in the index leg is the result of nonatherosclerotic comorbid conditions. 6.Conditions other than IC of significant severity that could confound peak walking time on the standardized exercise treadmill test causing premature or inconsistent termination of exercise (eg, angina pectoris, heart failure [New York Heart Association {NYHA} Classes III and IV], respiratory disease [eg, chronic obstructive pulmonary disease], orthopedic disease, neurological disorders, rheumatologic disorders [eg, severe degenerative joint diseases], dyspnea, fatigue, prior lower limb amputation, including amputations proximal to the metatarsal or phalangeal joints). 7.Presence or history of cancer within 5 years or not current with American Cancer Society (ACS) (or other nationally recognized) cancer screening guidelines, except low grade and fully resolved nonmelanoma skin malignancy. 8.Patients with a well defined clinical or genetic disorder predisposing to malignancy should be excluded (eg, von Hippel- Lindau, familial polyposis coli, BRCA1, BRCA2, etc). 9.Patients with baseline funduscopic evidence of active proliferative diabetic retinopathy, preproliferative diabetic retinopathy, or wet age-related macular degeneration (AMD) AND/OR Patients with a history of treatment for active proliferative diabetic retinopathy or wet AMD within 5 years of study participation. 10.Diabetes type 1 (juvenile onset). 11.Poorly controlled type 2 diabetes (ie, HbA1C > 10%) at Screening. 12.Active hepatitis defined as clinically significant increase in liver enzymes (ie, 3 times the upper limit of normal [ULN]) or other current infectious disease. 13.Patients with symptoms of respiratory infection at time of Screening and/or randomization period and/or patients who have been on systemic or oral antibiotics for active infection within 2 weeks of study drug administration. 14.Patients with clinically significant abnormal hematology (eg, hematocrit 14,000), blood chemistry, renal, hepatic, or other laboratory parameters that could be the result of an underlying malignancy or systemic infection (eg, serum creatinine = 2.5 mg/dL), as judged by the investigator. 15.Patients with the following comorbidities who may not be healthy enough to successfully complete all protocol requirements or in whom results may be particularly difficult to assess: •Concurrent severe congestive heart failure (NYHA Classes III and IV), •Life-threatening ventricular arrhythmias, unstable angina and/or myocardial infarction within 4 weeks before Enrollment, •Coronary artery bypass grafting or percutaneous coronary intervention within 3 months before Enrollment, •Transient ischemic attack within 3 months before Enrollment, •Deep vein thrombosis within 3 months, •Severe chronic obstruct
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the safety of an experimental gene transfer agent, Ad2/HIF-1a/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). This is done by assessing: • the safety and tolerability of 3 doses of Ad2/HIF-1a/VP16 compared to Placebo-control in the treatment of severe intermittent claudication (IC) • the efficacy of 3 doses of Ad2/HIF-1a/VP16 compared to Placebo-control in the treatment of severe IC ;Secondary Objective: This study is being conducted to: •Provide a basis for optimal dose selection for Phase 3 studies •Provide a basis for patient population, safety and efficacy parameters, and sample size determinations for Phase 3 studies ;Primary end point(s): The safety data collected for the Phase 2 therapeutic dose-selection study include: 1.AEs and vital signs -Adverse vascular events 2.Clinical laboratory parameters -Hematology, liver function tests, renal function test, blood chemistry (including EPO -PSA, occult blood in stool 3.Selected cancer screening 4.Antibody titels and neutralizing antibody titers 5.Eye examinations 6.Potential adenoviral vector circulation within the blood 7.Potential adenoviral vector shedding The primary efficacy variable is: Change form Baseline to week 26 in PWT using a standardized exercise treadmill test | — |
Countries
Germany, United Kingdom
Outcome results
None listed