Efficacy and Safety Study of NV1FGF in Patients With Severe Peripheral Artery Occlusive Disease (TALISMAN 201)

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Efficacy and Safety Study of NV1FGF in Patients With Severe Peripheral Artery Occlusive Disease.

This study is a double-blind study to evaluate the efficacy and safety of NV1FGF, a pCOR plasmid constructed by inserting the gene coding for the FGF compared to placebo in patients with severe Peripheral Arterial Occlusive Disease, Fontaine's stage IV. The efficacy was assessed by the complete healing of at least one ulcer in the treated limb, 25 week post-baseline and secondary by the rate of amputation and death.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium
    • Ghent University Hospital
• France
  • Paris, France
    • Hôpital Europeén Georges Pompidou
• Germany
  • Karlsbad, Germany
    • Klinikum Karlsbad-Langensteinbach
• Italy
  • Roma, Italy
    • Istituto Dermopatico dell'Immacolata
• Switzerland
  • Bern, Switzerland
    • Universitätsklinik
• United Kingdom
  • London, United Kingdom
    • St George's Hospital

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:

• Outpatients with severe Peripheral Artery Occlusive Disease defined as Rutherford's Grade III, category 5 or 6, or Fontaine's stage IV.
• Trophic lesions with no signs of healing (no reduction in ulcer size or depth) for at least 2 weeks prior to first study treatment administration (Day 1).
• Patients with objective evidence of peripheral vascular disease (resting ankle pressure < 70 mmHg and/or toe pressure < 50 mmHg, and/or resting ankle-brachial index (ABI) < 0.4 and/or resting toe-brachial index (TBI) < 0.3 and/or metatarsal pulse volume recording (PVR) flat or barely pulsatile) in the diseased limb on two consecutive examinations performed at least 1 week apart.
• Demonstration or documentation (historical data not older than 6 months prior to first study treatment administration) of total occlusion of the affected limb of one or more of the iliac, superficial femoral, popliteal and/or one or more infrapopliteal arteries as assessed by angiography.
• Life expectancy > 6 months from the first study treatment administration.
• Poor/not candidates for revascularization (patients suitable for revascularization but with a high risk of failure/ amputation/ or patients not suitable for revascularization).

Exclusion Criteria:

• Previous or current history of malignant disease. Patients who had successful tumor resection or radio-chemotherapy more than 5 years prior to inclusion in the study and no recurrence will be allowed for inclusion.
• Suspicion of malignant disease (abnormal X ray,positive. stool hemoccult, positive Prostate Specific Antigen , abnormal mammography, papanicolaou smear of Class IV or Class V characterization.
• Lower extremity surgery : bypass/angioplasty of the leg to be treated within 2 months prior to the first administration of study treatment (Day 1).
• Active proliferative retinopathy.
• Buerger's disease

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Primary efficacy parameter: ulcer healing.
Ulcers will be evaluated at each visit primarily by collecting quantitative and qualitative information.

Secondary Outcome Measures

Outcome Measure
Pain
Death
Hemodynamic parameters:ABI, TcPO2
Amputation (Date of amputation, Indication for amputation, amputation level (minor and major)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Principal Investigator: Sigrid NIKOL, Prof., Universitätsklinikum Münster

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.
• Nikol S, Baumgartner I, Van Belle E, Diehm C, Visona A, Capogrossi MC, Ferreira-Maldent N, Gallino A, Wyatt MG, Wijesinghe LD, Fusari M, Stephan D, Emmerich J, Pompilio G, Vermassen F, Pham E, Grek V, Coleman M, Meyer F; TALISMAN 201 investigators. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther. 2008 May;16(5):972-8. doi: 10.1038/mt.2008.33. Epub 2008 Apr 1.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (Actual): April 1, 2005
• Study Completion (Actual): April 1, 2005

Study Registration Dates

• First Submitted: August 24, 2006
• First Submitted That Met QC Criteria: August 24, 2006
• First Posted (Estimate): August 25, 2006

Study Record Updates

• Last Update Posted (Estimate): November 18, 2008
• Last Update Submitted That Met QC Criteria: November 14, 2008
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: Gene Therapy; CLI; PAOD
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: DFI6143; NV1FGF-PM201