Peripheral Arterial Occlusive Disease
Conditions
Brief 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
Detailed description
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
Interventions
DRUGXRP0038 (NV1FGF)
Pharmaceutical form : solution Route of administration : intramuscular
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Detection of FGF-1 mRNA (by real-time RT-PCR) in injected tissues at injection site | 3 to 8 days after amputation |
Secondary
| Measure | Time frame |
|---|---|
| Detection of FGF-1 protein (by immunohistochemistry) in injected tissues (injection and remote site) | 3 to 8 days after amputation |
| Detection of FGF-1 mRNA (by real-time RT-PCR) in injected tissues at remote site | 3 to 8 days after amputation |
| Detection of FGF-1 receptor (by immunohistochemistry) in injected tissues (injection and remote site) | 3 to 8 days after amputation |
| Detection of NV1FGF (by real-time PCR) in injected tissues (injection and remote site), in multiple organs/tissues when appropriate, and in plasma | 2 months |
| Evaluation of healing of the amputation site | 6 months |
Countries
Switzerland, United States
Outcome results
None listed