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

Primary Purpose

Peripheral Arterial Occlusive Disease

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

XRP0038 (NV1FGF)

About this trial

This is an interventional treatment trial for Peripheral Arterial Occlusive Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

NV1FGF 500 μg

NV1FGF 2000 μg

NV1FGF 4000 μg

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Detection of FGF-1 protein (by immunohistochemistry) in injected tissues (injection and remote site)

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

Detection of FGF-1 receptor (by immunohistochemistry) in injected tissues (injection and remote site)

Detection of NV1FGF (by real-time PCR) in injected tissues (injection and remote site), in multiple organs/tissues when appropriate, and in plasma

Evaluation of healing of the amputation site

Full Information

NCT ID

NCT01157143

First Posted

July 2, 2010

Last Updated

July 2, 2010

Sponsor

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT01157143

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2010

Overall Recruitment Status

Completed

Study Start Date

January 2002 (undefined)

Primary Completion Date

October 2003 (Actual)

Study Completion Date

October 2003 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Sanofi

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral Arterial Occlusive Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NV1FGF 500 μg

Arm Type

Experimental

Arm Description

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

Arm Title

NV1FGF 2000 μg

Arm Type

Experimental

Arm Description

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

Arm Title

NV1FGF 4000 μg

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

XRP0038 (NV1FGF)

Intervention Description

Pharmaceutical form : solution Route of administration : intramuscular

Primary Outcome Measure Information:

Title

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

Time Frame

3 to 8 days after amputation

Secondary Outcome Measure Information:

Title

Detection of FGF-1 protein (by immunohistochemistry) in injected tissues (injection and remote site)

Time Frame

3 to 8 days after amputation

Title

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

Time Frame

3 to 8 days after amputation

Title

Detection of FGF-1 receptor (by immunohistochemistry) in injected tissues (injection and remote site)

Time Frame

3 to 8 days after amputation

Title

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

Title

Evaluation of healing of the amputation site

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

International Clinical Development Clinical Study Director

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

City

Minneapolis

State/Province

Minnesota

Country

United States

City

Bern

Country

Switzerland

12. IPD Sharing Statement

Citations:

PubMed Identifier

21716303

Citation

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.

Results Reference

derived

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

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