44496
document
A randomized , double-blind , placebo-controlled , phase I study of MEDI-545 , an anti-interferon-alfa monoclonal antibody , in subjects with chronic psoriasis . 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 .
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
MEDI-545
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Intervention_Pharmacological
MEDI-545
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
MEDI-545
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Intervention_Control
placebo
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Intervention_Pharmacological
MEDI-545
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Intervention_Control
placebo
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Intervention_Pharmacological
MEDI-545
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Intervention_Pharmacological
MEDI-545
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Intervention_Pharmacological
MEDI-545
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Intervention_Pharmacological
MEDI-545
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Outcome_Other
safety profile
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Outcome_Other
pharmacokinetics
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Outcome_Physical
immunogenicity
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Outcome_Other
clinical effects
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Outcome_Adverse-effects
adverse events
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Outcome_Adverse-effects
drug-related hypotensive infusion reaction
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Outcome_Physical
myocardial infarction
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Outcome_Other
half-life