A randomized, double-blind, placebo-controlled phase 1 study of multiple ascending doses of subcutaneous M1095, an anti-interleukin 17A/F nanobody, in moderate-to-severe psoriasis.

Abstract

Interleukin 17 is involved in the pathogenesis of psoriasis, a chronic debilitating disease. To evaluate the safety/tolerability, immunogenicity, pharmacokinetics/pharmacodynamics, and efficacy of M1095, an anti-interleukin 17A/F nanobody, in moderate-to-severe plaque psoriasis. This multicenter, double-blind, placebo-controlled dose escalation phase 1 study randomized 44 patients 4:1 to treatment with subcutaneous M1095 (30, 60, 120, or 240 mg) or placebo biweekly for 6 weeks, in 4 ascending dose cohorts. The most frequent treatment-emergent adverse events with M1095 were pruritus (n = 4) and headache (n = 3); 2 patients withdrew owing to adverse events (injection site reaction and elevated liver enzyme levels). The terminal half-life of M1095 was 11 to 12 days. The area under the curve/maximum concentration was dose proportional. Of 10 M1095-treated patients positive for antidrug antibodies, 5 showed treatment-emergent antidrug antibody responses. There was no effect on M1095 exposure. Marked decreases in psoriasis inflammatory markers were observed with M1095. By day 85, 100% and 56% of patients receiving M1095, 240 mg, achieved psoriasis area and severity index 90 and 100, respectively. Improvements in static Physician's Global Assessment and affected body surface area were also seen. Interpretation of efficacy data is limited by the small sample size. Multiple subcutaneous doses of M1095 showed a favorable safety profile with dose-dependent improvements in psoriasis.