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 - 21/06/19
, James G. Krueger, MD cAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : ALX-0761, interleukin 17, M1095, nanobody, phase 1, psoriasis
Abbreviations used : ADA, AE, BSA, IL, PASI, sPGA, TEAE
Plan
| Funding sources: This study was sponsored by Merck KGaA, Darmstadt, Germany. |
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| Disclosure: Dr Lubell and Mr Mackenzie were employees of EMD Serono, US (a business of Merck KGaA, Darmstadt, Germany) at the time of the study. Ms Casset-Semanaz and Dr Grenningloh are employees of EMD Serono, US (a business of Merck KGaA, Darmstadt, Germany). Ms Svecova declares no conflicts of interest. Dr Krueger's institution (Rockefeller University) received a research grant to fund part of this study, and he has been a consultant to Amgen, Lilly, Novartis, and UCB related to the development of interleukin 17–targeted therapeutics. |
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| The data in this manuscript were presented as a poster at the American Association of Dermatology annual meeting, Orlando, FL, March 3-7, 2017. |
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| Reprints not available from the authors. |
Vol 81 - N° 1
P. 196-203 - juillet 2019 Retour au numéro
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