Efficacy and Safety of XRP0038/NV1FGF in Critical Limb Ischemia Patients With Skin Lesions

NCT ID: NCT00566657

Last Updated: 2016-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 525 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2012-08-31

Brief Summary

Primary objective is to demonstrate the superiority of riferminogene pecaplasmid (XRP0038/NV1FGF) over placebo in the prevention of major amputation above the ankle of the treated leg or of death from any cause, whichever comes first, in critical limb ischemia (CLI) patients with skin lesions.

Secondary objectives are to evaluate:

• The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to major amputation;
• The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to death;
• The safety of riferminogene pecaplasmid in the study population.

Detailed Description

The study consists in 6-week treatment then a follow-up period up to 12 months. A follow-up contact is then scheduled 6 months later.

Per protocol amendment a 18-month long-term safety survey was added.

Conditions

Peripheral Vascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Riferminogene pecaplasmid

4 administrations of riferminogene pecaplasmid 4 mg at 2-week intervals

Group Type: EXPERIMENTAL

riferminogene pecaplasmid

Intervention Type: BIOLOGICAL

Formulation: 5 ml glass vials containing 2,5 ml riferminogene pecaplasmid

Route: intramuscular (IM) injection of 2.5 mL in the ischemic leg to be treated

Placebo

4 administrations of placebo (for riferminogene pecaplasmid) at 2-week intervals

Group Type: PLACEBO_COMPARATOR

Placebo (for riferminogene pecaplasmid)

Intervention Type: BIOLOGICAL

Formulation: 5 ml glass vials containing 2,5 ml placebo

Route: IM injection of 2.5 mL in the ischemic leg to be treated

Interventions

riferminogene pecaplasmid

Formulation: 5 ml glass vials containing 2,5 ml riferminogene pecaplasmid

Route: intramuscular (IM) injection of 2.5 mL in the ischemic leg to be treated

Intervention Type: BIOLOGICAL

Placebo (for riferminogene pecaplasmid)

Formulation: 5 ml glass vials containing 2,5 ml placebo

Route: IM injection of 2.5 mL in the ischemic leg to be treated

Intervention Type: BIOLOGICAL

Other Intervention Names

NV1FGF; XRP0038

Eligibility Criteria

Inclusion Criteria

• Having peripheral artery disease at the stage of Critical Limb Ischemia (CLI) with skin lesions (either ulcer(s) or gangrene);
• With objective evidence of CLI such as ankle systolic pressure <70 mmHg and/or toe systolic pressure <50 mmHg or transcutaneous oxygen pressure (TcPO2) <30 mmHg;
• Unsuitable for standard revascularization of his/her peripheral arterial disease;
• Having a negative screening for cancer.

Exclusion Criteria

• Previous major amputation on the leg to be treated or planned major amputation within the first month following randomization;
• Known Buerger's disease;
• Successful lower extremity revascularization procedure within 3 months prior randomization;
• Uncontrolled blood pressure defined as systolic blood pressure (SBP) ≥180 mmHg or diastolic blood pressure (DBP) ≥110 mmHg despite adequate antihypertensive treatment;
• Acute cardiovascular events within 3 months prior to randomization;
• Active proliferative retinopathy and severe macular oedema;
• Previous or current history of malignant disease within the past 5 years;
• Previous treatment with systemic angiogenic factors or with stem cells therapy;
• Pregnant or breast-feeding woman or woman of childbearing potential not protected by an effective contraceptive method of birth control. Man not following effective contraceptive method with his partner of childbearing potential during the course of the study.

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ICD CSD

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Sanofi-Aventis Administrative Office

Buenos Aires, , Argentina

Sanofi-Aventis Administrative Office

Macquarie Park, New South Wales, Australia

Sanofi-Aventis Administrative Office

Vienna, , Austria

Sanofi-Aventis Administrative Office

Minsk, , Belarus

Sanofi-Aventis Administrative Office

Diegem, , Belgium

Sanofi-Aventis Administrative Office

São Paulo, , Brazil

Sanofi-Aventis Administrative Office

Laval, , Canada

Sanofi-Aventis Administrative Office

Santiago, , Chile

Sanofi-Aventis Administrative Office

Prague, , Czechia

Sanofi-Aventis Administrative Office

Hørsholm, , Denmark

Sanofi-Aventis Administrative Office

Tatari, , Estonia

Sanofi-Aventis Administrative Office

Helsinki, , Finland

Sanofi-Aventis Administrative Office

Paris, , France

Sanofi-Aventis Administrative Office

Berlin, , Germany

Sanofi-Aventis Administrative Office

Athens, , Greece

Sanofi-Aventis Administrative Office

Causeway Bay, , Hong Kong

Sanofi-Aventis Administrative Office

Budapest, , Hungary

Sanofi-Aventis Administrative Office

Milan, , Italy

Sanofi-Aventis Administrative Office

Tokyo, , Japan

Sanofi-Aventis Administrative Office

México, , Mexico

Sanofi-Aventis Administrative Office

Warsaw, , Poland

Sanofi-Aventis Administrative Office

Moscow, , Russia

Sanofi-Aventis Administrative Office

Singapore, , Singapore

Sanofi-Aventis Administrative Office

Midrand, , South Africa

Sanofi-Aventis Administrative Office

Seoul, , South Korea

Sanofi-Aventis Administrative Office

Barcelona, , Spain

Sanofi-Aventis Administrative Office

Bromma, , Sweden

Sanofi-Aventis Administrative Office

Geneva, , Switzerland

Sanofi-Aventis Administrative Office

Istanbul, , Turkey (Türkiye)

Sanofi-Aventis Administrative Office

Kiev, , Ukraine

Sanofi-Aventis Administrative Office

Guildford, Surrey, United Kingdom

Countries

United States; Argentina; Australia; Austria; Belarus; Belgium; Brazil; Canada; Chile; Czechia; Denmark; Estonia; Finland; France; Germany; Greece; Hong Kong; Hungary; Italy; Japan; Mexico; Poland; Russia; Singapore; South Africa; South Korea; Spain; Sweden; Switzerland; Turkey (Türkiye); Ukraine; United Kingdom

References

Van Belle E, Nikol S, Norgren L, Baumgartner I, Driver V, Hiatt WR, Belch J. Insights on the role of diabetes and geographic variation in patients with critical limb ischaemia. Eur J Vasc Endovasc Surg. 2011 Sep;42(3):365-73. doi: 10.1016/j.ejvs.2011.04.030. Epub 2011 Jun 21.

Reference Type: RESULT

PMID: 21696982 (View on PubMed)

Belch J, Hiatt WR, Baumgartner I, Driver IV, Nikol S, Norgren L, Van Belle E; TAMARIS Committees and Investigators. Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia. Lancet. 2011 Jun 4;377(9781):1929-37. doi: 10.1016/S0140-6736(11)60394-2. Epub 2011 May 28.

Reference Type: RESULT

PMID: 21621834 (View on PubMed)

Other Identifiers

2006-006277-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC6145

Identifier Type: -

Identifier Source: org_study_id