BACKGROUND:Interferon-alfa (IFN-alpha) has been implicated in the pathogenesis of psoriasis. OBJECTIVE: To evaluate the safety profile of MEDI-545, a fully human anti-IFN-alpha monoclonal antibody and to explore its effect on the involvement of type I IFN-alpha activity in the maintenance of established plaque psoriasis. METHODS: We 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. RESULTS: There 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. LIMITATIONS: The study addressed only IFN-alpha and chronic psoriatic lesions. CONCLUSION: The safety profile of MEDI-545 supports further clinical development. IFN-alpha does not appear to be significantly involved in the maintenance of established plaque psoriasis. Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
RCT Entities:
BACKGROUND: Interferon-alfa (IFN-alpha) has been implicated in the pathogenesis of psoriasis. OBJECTIVE: To evaluate the safety profile of MEDI-545, a fully human anti-IFN-alpha monoclonal antibody and to explore its effect on the involvement of type I IFN-alpha activity in the maintenance of established plaque psoriasis. METHODS: We 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. RESULTS: There 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. LIMITATIONS: The study addressed only IFN-alpha and chronic psoriatic lesions. CONCLUSION: The safety profile of MEDI-545 supports further clinical development. IFN-alpha does not appear to be significantly involved in the maintenance of established plaque psoriasis. Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Authors: John C Hall; Livia Casciola-Rosen; Alan E Berger; Efstathia K Kapsogeorgou; Chris Cheadle; Athanasios G Tzioufas; Alan N Baer; Antony Rosen Journal: Proc Natl Acad Sci U S A Date: 2012-10-08 Impact factor: 11.205
Authors: Shereen Oon; Huy Huynh; Tsin Yee Tai; Milica Ng; Katherine Monaghan; Mark Biondo; Gino Vairo; Eugene Maraskovsky; Andrew D Nash; Ian P Wicks; Nicholas J Wilson Journal: JCI Insight Date: 2016-05-05