Efficacy and Safety of XRP0038/NV1FGF in Critical Limb Ischemia Patients With Skin Lesions

Study Overview
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Brief Summary
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Primary objective is to demonstrate the superiority of riferminogene pecaplasmid (XRP0038/NV1FGF) over placebo in the prevention of major amputation above the ankle of the treated leg or of death from any cause, whichever comes first, in critical limb ischemia (CLI) patients with skin lesions. Secondary objectives are to evaluate: The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to major amputation; The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to death; The safety of riferminogene pecaplasmid in the study population.

Detailed Description
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The study consists in 6-week treatment then a follow-up period up to 12 months. A follow-up contact is then scheduled 6 months later. Per protocol amendment a 18-month long-term safety survey was added.

Official Title
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A Randomized Double-Blind Placebo-Controlled Parallel Group Study of the Efficacy and Safety of XRP0038/NV1FGF on Amputation or Any Death in Critical Limb Ischemia Patients With Skin Lesions

Conditions
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Peripheral Vascular Diseases

Intervention / Treatment
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* Biological: riferminogene pecaplasmid
* Biological: Placebo (for riferminogene pecaplasmid)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having peripheral artery disease at the stage of Critical Limb Ischemia (CLI) with skin lesions (either ulcer(s) or gangrene); With objective evidence of CLI such as ankle systolic pressure <70 mmHg and/or toe systolic pressure <50 mmHg or transcutaneous oxygen pressure (TcPO2) <30 mmHg; Unsuitable for standard revascularization of his/her peripheral arterial disease; Having a negative screening for cancer. Exclusion Criteria: Previous major amputation on the leg to be treated or planned major amputation within the first month following randomization; Known Buerger's disease; Successful lower extremity revascularization procedure within 3 months prior randomization; Uncontrolled blood pressure defined as systolic blood pressure (SBP) ≥180 mmHg or diastolic blood pressure (DBP) ≥110 mmHg despite adequate antihypertensive treatment; Acute cardiovascular events within 3 months prior to randomization; Active proliferative retinopathy and severe macular oedema; Previous or current history of malignant disease within the past 5 years; Previous treatment with systemic angiogenic factors or with stem cells therapy; Pregnant or breast-feeding woman or woman of childbearing potential not protected by an effective contraceptive method of birth control. Man not following effective contraceptive method with his partner of childbearing potential during the course of the study. 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: 50 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: Riferminogene pecaplasmid<br>4 administrations of riferminogene pecaplasmid 4 mg at 2-week intervals | Biological: riferminogene pecaplasmid<br>* Formulation: 5 ml glass vials containing 2,5 ml riferminogene pecaplasmid Route: intramuscular (IM) injection of 2.5 mL in the ischemic leg to be treated<br>* Other names: XRP0038;|
| Placebo Comparator: Placebo<br>4 administrations of placebo (for riferminogene pecaplasmid) at 2-week intervals | Biological: Placebo (for riferminogene pecaplasmid)<br>* Formulation: 5 ml glass vials containing 2,5 ml placebo Route: IM injection of 2.5 mL in the ischemic leg to be treated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to major amputation of the treated leg or death from any cause, whichever comes first |  | From randomization up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first major amputation of the treated leg |  | From randomization up to 12 months | 
| Time to death from any cause |  | From randomization up to 12 months | 
| Number of participants with adverse events as a measure of safety |  | From 1st treatment administration up to death, or the earliest of Day 360 or last contact/assessment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmid based gene therapy, Critical Limb Ischemia, Peripheral Artery Disease