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
| Autor: | Harald Mackenzie, Martin W. Lubell, D Svecova, James G. Krueger, Florence Casset-Semanaz, Roland Grenningloh |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Maximum Tolerated Dose Injections Subcutaneous Dermatology Placebo Risk Assessment Severity of Illness Index Gastroenterology Drug Administration Schedule Young Adult 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Double-Blind Method Reference Values Psoriasis Area and Severity Index Psoriasis Internal medicine Injection site reaction Humans Medicine Dose-Response Relationship Drug business.industry Interleukin-17 Area under the curve Antibodies Monoclonal Middle Aged medicine.disease Treatment Outcome Tolerability 030220 oncology & carcinogenesis Pharmacodynamics Female Patient Safety Interleukin 17 business Follow-Up Studies |
| Zdroj: | Journal of the American Academy of Dermatology. 81:196-203 |
| ISSN: | 0190-9622 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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