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01.12.2014 | Study protocol | Ausgabe 1/2014 Open Access

BMC Cardiovascular Disorders 1/2014

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

Zeitschrift:
BMC Cardiovascular Disorders > Ausgabe 1/2014
Autoren:
Helen M Colhoun, Jennifer G Robinson, Michel Farnier, Bertrand Cariou, Dirk Blom, Dean J Kereiakes, Christelle Lorenzato, Robert Pordy, Umesh Chaudhari
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1471-2261-14-121) contains supplementary material, which is available to authorized users.

Competing interests

The ODYSSEY COMBO studies were supported by Sanofi and Regeneron Pharmaceuticals, Inc.
HMC is a consultant or on an advisory panel for Pfizer, Sanofi Aventis, Regeneron, Novartis, and Eli Lilly, has received research support from Roche, Pfizer, Eli Lilly, Boehringer Ingelheim, and AstraZeneca, has participated in a lecture/speaker’s bureau and received honorarium from Pfizer, and is a shareholder in Roche.
JGR is employed by a university that has received research funds from Amarin, Amgen, AstraZeneca, Daiichi-Sankyo, Genetech/Hoffman La Roche, Glaxo-Smith Kline, Merck, Regeneron/Sanofi, and Zinfandel/Takeda, and is a consultant for Amgen, Hoffman La Roche, Merck, Pfizer, Sanofi, and Regeneron.
MF has received grant/research support and speaker’s honoraria from Amgen, Merck and Sanofi, has received honoraria from Abbott, Eli Lilly and Pfizer, and served as a consultant and advisor for Amgen, Astra Zeneca, Kowa, Merck, Recordati, Roche, Sanofi/Regeneron, and SMB.
BC has received research funds from Sanofi Aventis, and is a consultant or on an advisory panel for Amgen, Astra-Zeneca, DebioPharm, Janssen, Eli Lilly, Genfit, Novo-Nordisk and Sanofi-Aventis.
DB is a consultant or on an advisory panel for Aegerion, Amgen, AstraZeneca, MSD, and Sanofi Aventis. DB’s institution has received payment for conducting clinical trials from Aegerion, Amgen, Eli Lilly, Novartis, and Sanofi/Regeneron. DB has participated in a lecture/speaker’s bureau or received honoraria from Aegerion, Amgen, AstraZeneca, MSD, Pfizer, Sanofi Aventis, Servier, and Unilever.
DJK has received consulting fees from Medpace, HCRI, Ablative Solutions, Inc., Boston Scientific, Abbott Vascular, and REVA Medical Inc.
CL and UC are employees of Sanofi.
RP is an employee of Regeneron Pharmaceuticals, Inc.

Authors’ contributions

HMC, JGR, MF, CL, RP and UC were involved in the design and coordination of the study. BC, DB and DJK were involved in the coordination of the study and recruitment of patients, and are involved in the ongoing collection of data. CL developed the statistical analysis plan. HMC, JGR, MF, CL, RP and UC outlined the initial draft of the article. All authors have reviewed subsequent drafts of the manuscript throughout development and provided critical revisions. All authors read and approved the final manuscript.

Abstract

Background

Alirocumab 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/design

The 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).

Discussion

In 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 registrations

COMBO I: NCT01644175 (NCT01644175). COMBO II: NCT01644188 (NCT01644188).
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