Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials

BMC Cardiovascular Disorders

Study Protocol

Dirk Blom¹  Bertrand Cariou²  Michel Farnier³  Robert Pordy⁴  Umesh Chaudhari⁵  Christelle Lorenzato⁶  Dean J Kereiakes⁷  Helen M Colhoun⁸  Jennifer G Robinson⁹ 

[1] Division of Lipidology, Department of Medicine, University of Cape Town and MRC Cape Heart Group, Cape Town, South Africa;L’Institut du Thorax, CHU de Nantes, Nantes, France;Point Médical, Dijon, France;Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA;Sanofi, Bridgewater, NJ, USA;Sanofi, Paris, France;The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, Cincinnati, OH, USA;University of Dundee, DD2 4BF, Dundee, Scotland, UK;University of Iowa, Iowa City, IA, USA;

关键词: Alirocumab;    Ezetimibe;    Low-density lipoprotein cholesterol;    Monoclonal antibody;    Proprotein convertase subtilisin kexin type 9;   

DOI  :  10.1186/1471-2261-14-121

 received in 2014-06-19, accepted in 2014-09-11,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundAlirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 (PCSK9) under investigation for treatment of hypercholesterolemia and reduction of cardiovascular events.Methods/designThe COMBO studies, part of the Phase 3 ODYSSEY clinical trial program, are designed to evaluate the efficacy and safety of alirocumab as add-on therapy to stable, maximally tolerated daily statin, with or without other lipid-lowering therapy (LLT), in a planned 966 patients with hypercholesterolemia at high cardiovascular risk. COMBO I (http://clinicaltrials.gov/show/NCT01644175) is placebo-controlled, with a double-blind treatment period of 52 weeks, and 306 planned patients who may receive other LLTs in addition to statin therapy. COMBO II (http://clinicaltrials.gov/show/NCT01644188) has a double-blind treatment period of 104 weeks, comparing alirocumab with ezetimibe in 660 planned patients receiving statin therapy (but no other LLTs). The primary efficacy endpoint is the difference between treatment arms in percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 24. Both studies utilized a starting dose of alirocumab 75 mg every 2 weeks (Q2W; administered as 1 mL solution via auto-injector). Patients with LDL-C levels ≥70 mg/dL after 8 weeks of treatment were up-titrated in a blinded manner at week 12 to alirocumab 150 mg Q2W (also 1 mL auto-injector).DiscussionIn conclusion, the COMBO studies will provide information on the long-term efficacy and safety of alirocumab in high-risk patients when administered in addition to maximally tolerated statin therapy, with a flexible dosing strategy which allows for individualized therapy based on the degree of LDL-C lowering needed to achieve the desired treatment response.Trial registrationsCOMBO I: NCT01644175 (NCT01644175). COMBO II: NCT01644188 (NCT01644188).

【 授权许可】

CC BY   
© Colhoun et al.; licensee BioMed Central Ltd. 2014