Dose-finding, Safety and Efficacy Study of NV1FGF in Patients With Intermittent Claudication

Study Overview
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Brief Summary
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The primary objective is to assess safety and efficacy of two different doses of NV1FGF as compared to placebo. The secondary objective is to assess the pharmacokinetics of NV1FGF and FGF-1 protein.

Detailed Description
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Screening of 1 to 4 weeks before study drug administration; 6 weeks of treatment, followed by 20 weeks of follow-up.

Official Title
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Double-blind, Randomized, Placebo-controlled, Parallel Group and Dose-finding, Multicentric, Safety and Efficacy Study With Intramuscular Injections of NV1FGF in Subjects With Intermittent Claudication

Conditions
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Peripheral Arterial Occlusive Disease

Intervention / Treatment
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* Drug: XRP0038 (NV1FGF)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age>40 years History of typical intermittent claudication lasting for at least 3 months, showing no improvement and consistent with treadmill test findings Objective evidence of Peripheral Arterial Occlusive Disease. After 10 minutes of rest, either by Ankle brachial index measure (ABI) <0.8 or Systolic ankle pressure (AP) < 50 mmHg or Systolic toe pressure <50 mmHg Patent femoral inflow above the level of injections recently (<2 weeks) documented either with Doppler ultrasonography or Magnetic Resonance Angiography or Angiography Exclusion criteria: Evidence of other causes for leg pain other than intermittent claudication. Illnesses limiting subject exercise capacity (angina pectoris, heart failure, respiratory disease, orthopaedic disease, neurological disorders…) Pain at rest Buerger's disease Positive serology for HIV 1 or 2, positive serology hepatitis B or C. Subjects with serum creatinine > 2 mg/dl (176 µmol/l) and subjects on dialysis. Active proliferative retinopathy defined by the presence of new vessel formation and scarring. Subjects who had a stroke or neurologic deficit presumed to be due to stroke within 3 months prior to the first administration of study treatment Previous treatment with any angiogenic growth factor Pregnant or breast feeding women or who disagree to practice a medically accepted method of birth control. Men and women who do not agree to use condoms as the only accepted protection barrier, for the entire study period Serious concomitant medical conditions not adequately controlled. Current alcohol or drug abuse The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 40 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: placebo<br>4 administrations at 2-week interval of placebo solution | Drug: placebo<br>* Pharmaceutical form:solution Route of administration: intramuscular<br>|
| Experimental: NV1FGF 16 mg<br>4 administrations at 2-week interval of 4mg at each administration | Drug: XRP0038 (NV1FGF)<br>* Pharmaceutical form:solution Route of administration: intramuscular<br>|
| Experimental: NV1FGF 32 mg<br>4 administrations at 2-week interval of 8mg at each administration | Drug: XRP0038 (NV1FGF)<br>* Pharmaceutical form:solution Route of administration: intramuscular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Absolute Claudication Distance (ACD) evaluated by treadmill test at week 13 |  | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NV1FGF DNA 69 base pair (bp) in plasma |  | up to week 27 | 
| NV1FGF DNA 825 bp in plasma |  | up to week 27 | 
| FGF-1 in plasma |  | up to week 27 | 
| Anti-FGF1 antibodies in serum |  | up to week 27 |