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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT01157143
First received: July 2, 2010
Last updated: NA
Last verified: July 2010
History: No changes posted
  Purpose

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

Condition Intervention Phase
Peripheral Arterial Occlusive Disease
Drug: XRP0038 (NV1FGF)
Phase 1

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

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Detection of FGF-1 mRNA (by real-time RT-PCR) in injected tissues at injection site [ Time Frame: 3 to 8 days after amputation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Detection of FGF-1 protein (by immunohistochemistry) in injected tissues (injection and remote site) [ Time Frame: 3 to 8 days after amputation ] [ Designated as safety issue: No ]
  • Detection of FGF-1 mRNA (by real-time RT-PCR) in injected tissues at remote site [ Time Frame: 3 to 8 days after amputation ] [ Designated as safety issue: No ]
  • Detection of FGF-1 receptor (by immunohistochemistry) in injected tissues (injection and remote site) [ Time Frame: 3 to 8 days after amputation ] [ Designated as safety issue: No ]
  • Detection of NV1FGF (by real-time PCR) in injected tissues (injection and remote site), in multiple organs/tissues when appropriate, and in plasma [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Evaluation of healing of the amputation site [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: January 2002
Study Completion Date: October 2003
Primary Completion Date: October 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NV1FGF 500 μg
8 intramuscular injections for a total of 500 μg administered in one single administration 3 to 8 days before major amputation
Drug: XRP0038 (NV1FGF)

Pharmaceutical form : solution

Route of administration : intramuscular

Experimental: NV1FGF 2000 μg
8 intramuscular injections for a total of 2000 μg administered in one single administration 3 to 8 days before major amputation
Drug: XRP0038 (NV1FGF)

Pharmaceutical form : solution

Route of administration : intramuscular

Experimental: NV1FGF 4000 μg
8 intramuscular injections for a total of 4000 μg administered in one single administration 3 to 8 days before major amputation
Drug: XRP0038 (NV1FGF)

Pharmaceutical form : solution

Route of administration : intramuscular


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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01157143

Locations
United States, Minnesota
Minneapolis, Minnesota, United States
Switzerland
Bern, Switzerland
Sponsors and Collaborators
Sanofi
Investigators
Study Director: International Clinical Development Clinical Study Director Sanofi
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: International Clinical Development Study Director, sanofi-aventis
ClinicalTrials.gov Identifier: NCT01157143     History of Changes
Other Study ID Numbers: TED10105, PM105
Study First Received: July 2, 2010
Last Updated: July 2, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Peripheral Arterial Disease
Vascular Diseases
Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis
Peripheral Vascular Diseases

ClinicalTrials.gov processed this record on July 24, 2014