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

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


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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Subcutaneous
  • Interleukin-17 / antagonists & inhibitors*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Patient Safety
  • Psoriasis / diagnosis*
  • Psoriasis / drug therapy*
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult


  • Antibodies, Monoclonal
  • Interleukin-17