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J Am Acad Dermatol. 2019 Jul;81(1):196-203. doi: 10.1016/j.jaad.2019.03.056. Epub 2019 Mar 27.

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.

Author information

1
Faculty of Medicine of Comenius University, Bratislava, Slovakia.
2
EMD Serono Research and Development Institute, Billerica, Massachusetts.
3
EMD Serono Research and Development Institute, Billerica, Massachusetts. Electronic address: roland.grenningloh@emdserono.com.
4
Rockefeller University, New York, New York.

Abstract

BACKGROUND:

Interleukin 17 is involved in the pathogenesis of psoriasis, a chronic debilitating disease.

OBJECTIVES:

To evaluate the safety/tolerability, immunogenicity, pharmacokinetics/pharmacodynamics, and efficacy of M1095, an anti-interleukin 17A/F nanobody, in moderate-to-severe plaque psoriasis.

METHODS:

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.

RESULTS:

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.

LIMITATIONS:

Interpretation of efficacy data is limited by the small sample size.

CONCLUSION:

Multiple subcutaneous doses of M1095 showed a favorable safety profile with dose-dependent improvements in psoriasis.

KEYWORDS:

ALX-0761; M1095; interleukin 17; nanobody; phase 1; psoriasis

PMID:
30926369
DOI:
10.1016/j.jaad.2019.03.056
[Indexed for MEDLINE]
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