| | A randomized, double-blind, placebo-controlled, phase I study of MEDI-545, an anti–interferon-alfa monoclonal antibody, in subjects with chronic psoriasisAccepted 14 May 2009. BackgroundInterferon-alfa (IFN-α) has been implicated in the pathogenesis of psoriasis. ObjectiveTo evaluate the safety profile of MEDI-545, a fully human anti–IFN-α monoclonal antibody and to explore its effect on the involvement of type I IFN-α activity in the maintenance of established plaque psoriasis. MethodsWe conducted an 18-week, randomized, double-blind, placebo-controlled, dose-escalating study in 36 subjects with chronic plaque psoriasis. Subjects received one intravenous dose of MEDI-545 (0.3-30.0 mg/kg) or placebo. Study outcomes were safety profile, pharmacokinetics, immunogenicity, and clinical effects. ResultsThere was no difference in adverse events between MEDI-545 and placebo. Two serious adverse events were reported; one drug-related hypotensive infusion reaction occurred in one subject in the 30.0 mg/kg MEDI-545 dose group, causing discontinuation of study drug in that subject and study dismissal of the other subjects in the same cohort; and a myocardial infarction occurred in one subject in the 10 mg/kg MEDI-545 dose group, which was considered to be unrelated to treatment. MEDI-545 was nonimmunogenic, had a half-life of 21 days, showed no significant inhibition of the type I IFN gene signature, and had no clinical activity. LimitationsThe study addressed only IFN-α and chronic psoriatic lesions. ConclusionThe safety profile of MEDI-545 supports further clinical development. IFN-α does not appear to be significantly involved in the maintenance of established plaque psoriasis. Abbreviations used: AE, adverse event, BSA, body surface area, CL, (total body serum) clearance, DLQI, Dermatology Life Quality Index, HSV, herpes simplex virus, IFN, interferon, IV, intravenous, PASI, Psoriasis Area and Severity Index, PGA, Physician Global Assessment, SLE, systemic lupus erythematosus, TNF, tumor necrosis factor, VAS, visual analog scale a Innovaderm Research, Inc, Montreal, Quebec, Canada b Probity Medical Research, Waterloo, Ontario, Canada c Innovaderm Research, Inc, Laval, Quebec, Canada d MedImmune, LLC, Gaithersburg, Maryland  Reprint requests: Barbara White, MD, MedImmune, LLC, One MedImmune Way, Gaithersburg, MD 20878.
Supported by MedImmune, LLC. Disclosure: Drs Yao, Robbie, White, Le, and White are employees of MedImmune. Dr Bissonnette received research funding from MedImmune for this study; has received research funding, is a consultant, and/or has received honoraria from MedImmune, LLC, Amgen, Inc, Wyeth, Inc, Centocor/Schering-Plough, Ortho-Biotech, Abbott Laboratories, Astellas, and EMD Serono, Inc. Dr Papp received research funding from MedImmune for this study; has received research funding, is a consultant, Speaker Bureau, and/or investigator for MedImmune, Abbott Laboratories, Amgen, Inc, Celgene Corporation, Merck-Serono, Schering-Plough, and Wyeth, Inc. Dr Maari received research funding from MedImmune for this study; is a consultant and/or has received honoraria from Amgen, Inc, Wyeth, Inc, Centocor/Schering-Plough, Ortho-Biotech, Abbott Laboratories, Astellas, and Galderma. PII: S0190-9622(09)00686-0 doi:10.1016/j.jaad.2009.05.042 © 2009 American Academy of Dermatology, Inc. Published by Elsevier Inc All rights reserved. | |
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