gene expression and tolerability study of nv1fgf in patients with peripheral artery occlusive disease planned to undergo major amputation

Conditions: Peripheral Arterial Occlusive Disease

Summary: the primary objective is to evaluate the transgene expression (synthesis of fgf-1 mrna) in injected tissue, at injection site, after intra muscular (im) administration of increasing single doses of nv1fgf. secondary objectives : * to evaluate the safety and tolerability of im administration of increasing single doses of nv1fgf * to evaluate the transgene expression (fgf-1 protein) in injected tissues (injection site and remote site) * to evaluate the presence of fgf-1 receptors in injected tissues (injection site and remote site) * to evaluate the nv1fgf biodistribution in injected tissues (injection site and remote site), in multiple organs/tissues when appropriate, and plasma * to evaluate the transgene expression (synthesis of fgf-1 mrna) in injected tissue at remote site * to collect data from plasma nv1fgf pharmacokinetics * to evaluate healing of the amputation site

screening of 1 to 4 weeks before study drug administration; single study drug administration 3 to 8 days before planned amputation; 6 months of follow up

Eligibility criteria:
inclusion criteria: * subjects with prior decision for amputation above the ankle because of severe paod * males or females above 18 years * females must be either: * non pregnant, non lactating , having practicing a medically accepted method of birth control for more than 2 months prior screening visit; * or surgically sterilized (tubal ligation or hysterectomy) * or post menopausal for at least one year exclusion criteria: * subjects with urgent need for amputation that cannot await until completion of the screening period (up to 4 weeks), added to the minimum required 48 hours between study test medication administration and tissue sample collection * previous or current history of malignant disease (subjects with successful tumor resection more than 5 years -without any recurrence- prior to study start could be enrolled) * abnormal chest x-ray or mammography with suspicion of malignant disease * positive stool hemoccult (except in case of hemorrhoids or any other identified cause with no malignancy origin) * men with positive prostate specific antigen (psa) (above 2.5 ng/ml in subjects \< 50 years and above 5 ng/ml in subjects above 50 years) * females with papanicolaou smear of class iv or class v characterization * serious concomitant medical conditions not adequately controlled * alcohol or drug abuse * active proliferate retinopathy defined by the presence of new vessel formation and scarring * participation in clinical trials of non-approved experimental agents within four weeks before study entry; * positive serology for hiv1 or 2 * creatinine above 2.0 mg/dl (176 µmol/l), unless the subject is on hemodialysis / peritoneal dialysis and diagnosed with complete and irreversible renal failure or end-stage renal disease (esrd) * subjects who had a stroke or a neurological deficit presumably due to a stroke, within 3 months prior to study treatment (amendment #1) * alpha-fetoprotein (afp) in serum \> 15 µg/l, unless liver ultrasound ruled out any malignant disease * positive serology for hepatitis b or c, unless liver ultrasound ruled out any malignant disease. the above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.