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

• ClinicalTrials.gov Identifier: NCT00566657
• Recruitment Status: Completed
• First Posted: December 3, 2007
• Last Update Posted: May 2, 2016
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Peripheral Vascular Diseases	Biological: riferminogene pecaplasmid; Biological: Placebo (for riferminogene pecaplasmid)	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 525 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-Blind Placebo-Controlled Parallel Group Study of the Efficacy and Safety of XRP0038/NV1FGF on Amputation or Any Death in Critical Limb Ischemia Patients With Skin Lesions
• Study Start Date: November 2007
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Riferminogene pecaplasmid; 4 administrations of riferminogene pecaplasmid 4 mg at 2-week intervals	Biological: 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; Other Names: NV1FGF; XRP0038
Placebo Comparator: Placebo; 4 administrations of placebo (for riferminogene pecaplasmid) at 2-week intervals	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

Outcome Measures

Primary Outcome Measures :

1. Time to major amputation of the treated leg or death from any cause, whichever comes first [ Time Frame: From randomization up to 12 months ]

Secondary Outcome Measures :

1. Time to first major amputation of the treated leg [ Time Frame: From randomization up to 12 months ]
2. Time to death from any cause [ Time Frame: From randomization up to 12 months ]
3. Number of participants with adverse events as a measure of safety [ Time Frame: From 1st treatment administration up to death, or the earliest of Day 360 or last contact/assessment ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, New Jersey

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Argentina

Sanofi-Aventis Administrative Office

Buenos AIres, Argentina

Australia, New South Wales

Sanofi-Aventis Administrative Office

Macquarie Park, New South Wales, Australia

Austria

Sanofi-Aventis Administrative Office

Vienna, Austria

Belarus

Sanofi-Aventis Administrative Office

Minsk, Belarus

Belgium

Sanofi-Aventis Administrative Office

Diegem, Belgium

Brazil

Sanofi-Aventis Administrative Office

Sao Paulo, Brazil

Canada

Sanofi-Aventis Administrative Office

Laval, Canada

Chile

Sanofi-Aventis Administrative Office

Santiago, Chile

Czech Republic

Sanofi-Aventis Administrative Office

Praha, Czech Republic

Denmark

Sanofi-Aventis Administrative Office

Horsholm, Denmark

Estonia

Sanofi-Aventis Administrative Office

Tatari, Estonia

Finland

Sanofi-Aventis Administrative Office

Helsinki, Finland

France

Sanofi-Aventis Administrative Office

Paris, France

Germany

Sanofi-Aventis Administrative Office

Berlin, Germany

Greece

Sanofi-Aventis Administrative Office

Athens, Greece

Hong Kong

Sanofi-Aventis Administrative Office

Causeway Bay, Hong Kong

Hungary

Sanofi-Aventis Administrative Office

Budapest, Hungary

Italy

Sanofi-Aventis Administrative Office

Milan, Italy

Japan

Sanofi-Aventis Administrative Office

Tokyo, Japan

Korea, Republic of

Sanofi-Aventis Administrative Office

Seoul, Korea, Republic of

Mexico

Sanofi-Aventis Administrative Office

Mexico, Mexico

Poland

Sanofi-Aventis Administrative Office

Warszawa, Poland

Russian Federation

Sanofi-Aventis Administrative Office

Moscow, Russian Federation

Singapore

Sanofi-Aventis Administrative Office

Singapore, Singapore

South Africa

Sanofi-Aventis Administrative Office

Midrand, South Africa

Spain

Sanofi-Aventis Administrative Office

Barcelona, Spain

Sweden

Sanofi-Aventis Administrative Office

Bromma, Sweden

Switzerland

Sanofi-Aventis Administrative Office

Geneva, Switzerland

Turkey

Sanofi-Aventis Administrative Office

Istanbul, Turkey

Ukraine

Sanofi-Aventis Administrative Office

Kiev, Ukraine

United Kingdom

Sanofi-Aventis Administrative Office

Guildford, Surrey, United Kingdom

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: ICD CSD; Sanofi

More Information

Publications of Results:

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.

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.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00566657
• Other Study ID Numbers: EFC6145; 2006-006277-24 ( EudraCT Number )
• First Posted: December 3, 2007
• Last Update Posted: May 2, 2016
• Last Verified: March 2016

Keywords provided by Sanofi:

Critical Limb Ischemia; Peripheral Artery Disease; Plasmid based gene therapy

Additional relevant MeSH terms:

Vascular Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Ischemia; Pathologic Processes; Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases