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

Peripheral Vascular Diseases Clinical Trial

— TAMARIS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00566657
• Other study ID #: EFC6145
• Secondary ID: 2006-006277-24
• Status: Completed
• Phase: Phase 3
• First received: November 30, 2007
• Last updated: July 31, 2013
• Start date: November 2007
• Est. completion date: August 2012

Study information

• Verified date: July 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentRussia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

Primary objective is to demonstrate the superiority of riferminogene pecaplasmid 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 525
• Est. completion date: August 2012
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• Vascular Diseases

Intervention

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
• 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

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos AIres
Australia	Sanofi-Aventis Administrative Office	Macquarie Park	New South Wales
Austria	Sanofi-Aventis Administrative Office	Vienna
Belarus	Sanofi-Aventis Administrative Office	Minsk
Belgium	Sanofi-Aventis Administrative Office	Diegem
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Canada	Sanofi-Aventis Administrative Office	Laval
Chile	Sanofi-Aventis Administrative Office	Santiago
Czech Republic	Sanofi-Aventis Administrative Office	Praha
Denmark	Sanofi-Aventis Administrative Office	Horsholm
Estonia	Sanofi-Aventis Administrative Office	Tatari
Finland	Sanofi-Aventis Administrative Office	Helsinki
France	Sanofi-Aventis Administrative Office	Paris
Germany	Sanofi-Aventis Administrative Office	Berlin
Greece	Sanofi-Aventis Administrative Office	Athens
Hong Kong	Sanofi-Aventis Administrative Office	Causeway Bay
Hungary	Sanofi-Aventis Administrative Office	Budapest
Italy	Sanofi-Aventis Administrative Office	Milan
Japan	Sanofi-Aventis Administrative Office	Tokyo
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Mexico	Sanofi-Aventis Administrative Office	Mexico
Poland	Sanofi-Aventis Administrative Office	Warszawa
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
Singapore	Sanofi-Aventis Administrative Office	Singapore
South Africa	Sanofi-Aventis Administrative Office	Midrand
Spain	Sanofi-Aventis Administrative Office	Barcelona
Sweden	Sanofi-Aventis Administrative Office	Bromma
Switzerland	Sanofi-Aventis Administrative Office	Geneva
Turkey	Sanofi-Aventis Administrative Office	Istanbul
Ukraine	Sanofi-Aventis Administrative Office	Kiev
United Kingdom	Sanofi-Aventis Administrative Office	Guildford	Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Brazil,  Canada,  Chile,  Czech Republic,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (2)

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 i — View Citation

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.2011.04.0 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to major amputation of the treated leg or death from any cause, whichever comes first		From randomization up to 12 months	No
Secondary	Time to first major amputation of the treated leg		From randomization up to 12 months	No
Secondary	Time to death from any cause		From randomization up to 12 months	No
Secondary	Number of participants with adverse events as a measure of safety		From 1st treatment administration up to death, or the earliest of Day 360 or last contact/assessment	Yes