Peripheral Vascular Diseases
Conditions
Keywords
Critical Limb Ischemia, Peripheral Artery Disease, Plasmid based gene therapy
Brief summary
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
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.
Interventions
BIOLOGICALriferminogene pecaplasmid
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
BIOLOGICALPlacebo (for riferminogene pecaplasmid)
Formulation: 5 ml glass vials containing 2,5 ml placebo Route: IM injection of 2.5 mL in the ischemic leg to be treated
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Brazil, Canada, Chile, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Mexico, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States
Outcome results
None listed