Dose-finding, Safety and Efficacy Study of NV1FGF in Patients With Intermittent Claudication (TALISMAN 211)

Double-blind, Randomized, Placebo-controlled, Parallel Group and Dose-finding, Multicentric, Safety and Efficacy Study With Intramuscular Injections of NV1FGF in Subjects With Intermittent Claudication

The primary objective is to assess safety and efficacy of two different doses of NV1FGF as compared to placebo.

The secondary objective is to assess the pharmacokinetics of NV1FGF and FGF-1 protein.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Occlusive Disease
• Intervention / Treatment: Drug: placebo; Drug: XRP0038 (NV1FGF)

Detailed Description

Screening of 1 to 4 weeks before study drug administration; 6 weeks of treatment, followed by 20 weeks of follow-up.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
• Germany
  • Münster, Germany
• Switzerland
  • Bern, Switzerland
• United States
  • Minnesota
    • Minneapolis, Minnesota, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Age>40 years
• History of typical intermittent claudication lasting for at least 3 months, showing no improvement and consistent with treadmill test findings
• Objective evidence of Peripheral Arterial Occlusive Disease. After 10 minutes of rest, either by Ankle brachial index measure (ABI) <0.8 or Systolic ankle pressure (AP) < 50 mmHg or Systolic toe pressure <50 mmHg
• Patent femoral inflow above the level of injections recently (<2 weeks) documented either with Doppler ultrasonography or Magnetic Resonance Angiography or Angiography

Exclusion criteria:

• Evidence of other causes for leg pain other than intermittent claudication.
• Illnesses limiting subject exercise capacity (angina pectoris, heart failure, respiratory disease, orthopaedic disease, neurological disorders…)
• Pain at rest
• Buerger's disease
• Positive serology for HIV 1 or 2, positive serology hepatitis B or C.
• Subjects with serum creatinine > 2 mg/dl (176 µmol/l) and subjects on dialysis.
• Active proliferative retinopathy defined by the presence of new vessel formation and scarring.
• Subjects who had a stroke or neurologic deficit presumed to be due to stroke within 3 months prior to the first administration of study treatment
• Previous treatment with any angiogenic growth factor
• Pregnant or breast feeding women or who disagree to practice a medically accepted method of birth control. Men and women who do not agree to use condoms as the only accepted protection barrier, for the entire study period
• Serious concomitant medical conditions not adequately controlled.
• Current alcohol or drug abuse

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: placebo; 4 administrations at 2-week interval of placebo solution	Drug: placebo; Pharmaceutical form:solution Route of administration: intramuscular
Experimental: NV1FGF 16 mg; 4 administrations at 2-week interval of 4mg at each administration	Drug: XRP0038 (NV1FGF); Pharmaceutical form:solution Route of administration: intramuscular
Experimental: NV1FGF 32 mg; 4 administrations at 2-week interval of 8mg at each administration	Drug: XRP0038 (NV1FGF); Pharmaceutical form:solution Route of administration: intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Absolute Claudication Distance (ACD) evaluated by treadmill test at week 13	13 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
NV1FGF DNA 69 base pair (bp) in plasma	up to week 27
NV1FGF DNA 825 bp in plasma	up to week 27
FGF-1 in plasma	up to week 27
Anti-FGF1 antibodies in serum	up to week 27

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): August 1, 2005
• Study Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: July 6, 2010
• First Submitted That Met QC Criteria: July 6, 2010
• First Posted (Estimate): July 7, 2010

Study Record Updates

• Last Update Posted (Estimate): July 7, 2010
• Last Update Submitted That Met QC Criteria: July 6, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Intermittent Claudication; Arterial Occlusive Diseases
• Other Study ID Numbers: ACT6141; PM211 (Other Identifier: Gencell)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No