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

NCT01157143 | Completed Phase 1

• 2 other identifiers: TED10105PM105
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 2

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

Conditions

Peripheral Arterial Occlusive Disease

Outcome Measures

Primary Outcomes (1)

• Detection of FGF-1 mRNA (by real-time RT-PCR) in injected tissues at injection site

  3 to 8 days after amputation

Secondary Outcomes (5)

• 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

Study Arms (3)

NV1FGF 500 μg

EXPERIMENTAL

8 intramuscular injections for a total of 500 μg administered in one single administration 3 to 8 days before major amputation

Drug: XRP0038 (NV1FGF)

NV1FGF 2000 μg

EXPERIMENTAL

8 intramuscular injections for a total of 2000 μg administered in one single administration 3 to 8 days before major amputation

Drug: XRP0038 (NV1FGF)

NV1FGF 4000 μg

EXPERIMENTAL

8 intramuscular injections for a total of 4000 μg administered in one single administration 3 to 8 days before major amputation

Drug: XRP0038 (NV1FGF)

Interventions

XRP0038 (NV1FGF) DRUG

Pharmaceutical form : solution Route of administration : intramuscular

NV1FGF 2000 μg; NV1FGF 4000 μg; NV1FGF 500 μg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

Unknown Facility

Minneapolis, Minnesota, United States

Location

Unknown Facility

Bern, Switzerland

Location

Related Publications (1)

• Niebuhr A, Henry T, Goldman J, Baumgartner I, van Belle E, Gerss J, Hirsch AT, Nikol S. Long-term safety of intramuscular gene transfer of non-viral FGF1 for peripheral artery disease. Gene Ther. 2012 Mar;19(3):264-70. doi: 10.1038/gt.2011.85. Epub 2011 Jun 30.

  PMID: 21716303 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Occlusive Disease 1

Study Officials

• International Clinical Development Clinical Study Director

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 5, 2010
• Study Start: January 1, 2002
• Primary Completion: October 1, 2003
• Study Completion: October 1, 2003
• Last Updated: July 5, 2010

Record last verified: 2010-07

Locations

US (1); CH (1)