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

Peripheral Arterial Occlusive Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01157143
• Other study ID #: TED10105
• Secondary ID: PM105
• Status: Completed
• Phase: Phase 1
• First received: July 2, 2010
• Last updated: July 2, 2010
• Start date: January 2002
• Est. completion date: October 2003

Study information

• Verified date: July 2010
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: October 2003
• Est. primary completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arterial Occlusive Diseases
• Peripheral Arterial Disease
• Peripheral Arterial Occlusive Disease

Intervention

Drug:
• XRP0038 (NV1FGF)
Pharmaceutical form : solution Route of administration : intramuscular

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of FGF-1 mRNA (by real-time RT-PCR) in injected tissues at injection site		3 to 8 days after amputation	No
Secondary	Detection of FGF-1 protein (by immunohistochemistry) in injected tissues (injection and remote site)		3 to 8 days after amputation	No
Secondary	Detection of FGF-1 mRNA (by real-time RT-PCR) in injected tissues at remote site		3 to 8 days after amputation	No
Secondary	Detection of FGF-1 receptor (by immunohistochemistry) in injected tissues (injection and remote site)		3 to 8 days after amputation	No
Secondary	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	No
Secondary	Evaluation of healing of the amputation site		6 months	No