Critical Limb Ischemia with skin lesions MedDRA version: 14.0 Level: LLT Classification code 10058069 Term: Critical limb ischemia System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Product Name: NV1FGF
Product Code: XRP0038
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not assigned
CAS Number: Not assigned
Current Sponsor code: XRP0038
Other descriptive name:
Sponsors
sanofi-aventis recherche et développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients complying with the following criteria will be eligible for inclusion: 1. Aged > 50 years old 2. Having CLI with skin lesions (either ulcer(s) stable over the last 2 week interval or gangrene ie major tissue loss). 3. With objective evidence of CLI such as ankle systolic pressure less than 70 mmHg and/or toe systolic pressure less than 50 mmHg or TcPO2 less than 30 mm Hg and patent femoral inflow assessed preferably by angiography, magnetic resonance or CT angiography (or by Doppler ultra sonography if the documentation of an older angiography technique is available), in the 6 months prior to first study treatment administration. 4. Unsuitable for standard revascularization of his/her peripheral arterial disease (patient will be considered unsuitable for revascularization by a vascular surgeon when there is no good or lack of autologous material for grafting, or if there is an unfavorable anatomy, or a bad prognosis of the revascularization, such as the revascularization will only bring an incomplete perfusion of the foot, or if there will be at high risk of failure/amputation, or if there is a safety risk associated with the revascularization procedure). 5. Having a negative screening for cancer (including a complete physical examination of each system organs especially the skin but other than ischemic skin lesions, a haematology blood test, a chest X-ray, a stool hemoccult test and in the last 6 months prior to screening a measurement of the level of Prostate Specific Antigen for males, a mammography and a Pap test for females. Additional investigations may be required as per local guidelines for cancer screening or because of a family cancer history or high frequency of a cancer in a country). 6. Who have signed the 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 (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous major amputation on the leg to be treated. 2. Planned major amputation within the first month following randomization. 3. Infected gangrene involving the forefoot evidenced by imaging (Xray). 4. Known Buerger’s disease. 5. ulcers from venous or neuropathic origin if not associated with at least one ulcer from arterial origin 6. Successful lower extremity revascularization surgery (bypass or angioplasty of the leg to be treated, sympathicolysis, sympathectomy or neurostimulation) within 3 months prior to randomization. 7. Uncontrolled blood pressure defined as SBP > 180 mmHg or DBP >=110 mmHg despite adequate antihypertensive treatment. 8. Presence of a severe non cardiovascular co-morbid condition such that the patient is not expected to survive more than 12 months. 9. Acute cardiovascular events (e.g. myocardial infarctus (MI), stroke, recent coronary intervention) within 3 months prior to randomization. 10. Active/proliferative retinopathy or severe macular oedema. 11. Previous or current history of malignant disease within the past 5 years. Previous malignant disease of more than 5 years with relapse or therapy within the past 5 years. Patients with a known predisposition for neoplasms (e.g. Hippel-Lindau syndrome, familial adenomatous poliposis, BRCA1 or BRCA2 mutation and Li-Fraumeni syndrome). 12. Previous treatment with systemic growth angiogenic factors or stem cells therapy. 13. Geographical or social factors that may preclude appropriate compliance to study requirements (e.g.: patients living too far from investigational site). 14. Pregnant or breast-feeding woman or woman of childbearing potential not protected by effective contraceptive method of birth control. Men not following effective contraceptive method with their partner of childbearing potential during the course of the study. 15. Receipt of any investigational treatment (drug or device) within the previous 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to demonstrate the superiority of 4 administrations of XRP0038/NV1FGF 4mg at 2-week intervals 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 Objective: The secondary objectives of the study are to evaluate: -The efficacy of XRP0038/NV1FGF versus XRP0038/NV1FGF placebo for delaying the time to major amputation -The efficacy of XRP0038/NV1FGF versus XRP0038/NV1FGF placebo for delaying the time to death. -The safety of XRP0038/NV1FGF in the study population;Primary end point(s): The primary endpoint is major amputation of the treated leg or death from any cause, whichever comes first, over the 12 months study period. Major amputation is an amputation above the ankle. | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed