Gene Expression and Tolerability Study of NV1FGF in Patients With Peripheral Artery Occlusive Disease Planned to Undergo Major Amputation

Phase I, Double Blind, Parallel-Group, Multi-center, Gene Expression (Synthesis of FGF-1 mRNA) and Tolerability Study of Increasing Single Dose of NV1FGF Administered by Intra-Muscular Injection in Subjects With Severe Peripheral Artery Occlusive Disease (PAOD) Planned to Undergo Amputation Above the Ankle

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

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.