A Phase 3 Trial of Imsidolimab, a Monoclonal Antibody Therapy for Generalized Pustular Psoriasis

The design of a phase 3 clinical trial of imsidolimab for the treatment of generalized pustular psoriasis (GPP) was presented at the 2022 Annual Meeting of the American Academy of Dermatology (AAD), held from March 25 to 29, 2022 in Boston, Massachusetts.

GPP, a rare inflammatory disease, manifests as recurrent flares of erythematous and pustular rash, typically accompanied by general malaise, fever, hyperleukocytosis, and elevated C-reactive protein.

There are currently no therapies approved in the United States or European Union for the treatment of GPP.

Imsidolimab (ANB019) is a high-affinity, humanized, anti-interleukin (IL)-36 receptor (IL-36R) monoclonal antibody that is being developed to target GPP and other inflammatory dermatoses. This monoclonal antibody antagonizes IL-36 cytokine signaling, which has clear evidence of involvement in the pathogenesis of GPP.

To evaluate the safety and efficacy of imsidolimab in GPP, the presenting authors proposed the design of a phase 3, international, multicenter, randomized, double-blind, placebo-controlled trial called Gemini-1 (ANB019-301).

The study will recruit 45 adult patients aged 18 to80 years who have active GPP. Active GPP is defined as satisfying the European Rare and Severe Psoriasis Expert Network (ERASPEN) GPP criteria or a first episode GPP event with GPP Physician’s Global Assessment (GPPPGA) score of 3 or greater, affecting 5% or more of the body surface area with pustules excluding palms and soles, and polygenic risk score of 3 or more.

Participants will be randomly assigned in a 1:1:1 ratio to receive 1-time 750 mg intravenous imsidolimab, 300 mg intravenous imsidolimab, or placebo treatment.

The primary efficacy endpoint is GPPPGA score at 4 weeks, in which a score of 0 indicates clear and 1 almost clear. Individuals who do not respond or worsen by day 8 will be eligible to receive rescue therapy.

Participants will either enter the safety follow-up or rollover to the 24-week long-term extension trial, Gemini-2 (ANB019-302).

For the Gemini-2 study, participants who received imsidolimab will be stratified by whether they were a responder, partial responder, or needed rescue medication. Responders will be randomly assigned in a 1:1 ratio to receive 200 mg subcutaneous imsidolimab or placebo, partial responders will receive 200 mg subcutaneous imsidolimab, and those who need rescue will receive any available therapy. For the placebo group, the responders and partial responders will receive same treatments as the imsidolimab cohort. The placebo recipients who need rescue medication will receive 750 mg intravenous imsidolimab on day 1 followed by 200 mg subcutaneous imsidolimab. Treatments will be administered every 4 weeks for 20 weeks. At week 24, participants will enter the safety follow-up until week 32.

Clinicians with patients who may benefit from enrolling in this trial are encouraged to contact Innovaderm Research for more information.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Gudjonsson JE, Randazzo B, Zhou J, Peterson R, Lizzul P. Imsidolimab in the treatment of adult subjects with generalized pustular psoriasis: Design of a pivotal phase 3 clinical trial and a long-term extension study. Presented at: the 2022 Annual Meeting; March 25-29, 2022. Abstract/Poster 34617.