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-α) has been implicated in the pathogenesis of psoriasis.

Objective

To 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.

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-α and chronic psoriatic lesions.

Conclusion

The 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