InflaRx N.V. announced details related to the design of its planned Phase III study with vilobelimab in ulcerative PG, a rare neutrophilic and inflammatory skin disease with destructive, painful cutaneous ulcers. The planned Phase III study is designed to enroll patients in the US, Europe and selected countries in other regions. The enrollment period is projected to be at least two years, depending on the total trial size after sample size adaptation.

The design is based on detailed feedback and recommendations from the FDA Division of Dermatology and Dentistry and was developed in close collaboration with the Company´s advisors from the US, Europe and other regions. The multi-national, randomized, double-blind, placebo-controlled Phase III trial will have two arms: vilobelimab (2400mg every other week) plus a low dose of corticosteroids and placebo plus the same low dose of corticosteroids. In both arms, corticosteroid treatment will be initiated on day 1 and will be tapered off within the first 8 weeks of the trial.

The primary endpoint of the study will be complete closure of the target ulcer at any time up to 26 weeks after initiation of treatment. Treatment will be discontinued for patients whose disease progresses or fails to improve at defined time points during the study. The study has an adaptive trial design with an interim analysis blinded for the sponsor and investigators (but unblinded for the independent data safety monitoring committee) planned upon enrollment of approximately 30 patients (15 per arm).

The interim analysis with a set of predefined rules will take into account the then-observed difference in complete target ulcer closure between the two arms and, accordingly, the trial sample size will be adapted or the trial will be stopped due to futility. As previously announced, the Company recently conducted a multi-center, proof-of-concept Phase IIa study with a total of 19 patients. Over a period of 26 weeks, patients were treated biweekly with vilobelimab 800mg, 1600mg or 2400mg, after an initial run-in phase with three doses of 800mg on days 1, 4 and 8, followed by a two-month observation period.

Efficacy was assessed with the physician global assessment score (PGA). In the high dose cohort, 6 out of 7 patients (85.7%) demonstrated complete target ulcer closure, and treatment response rates in the different dosing cohorts correlated with suppression of C5a levels in patients' plasma over time. The Company has received Fast Track and Orphan Drug (OD) designations by the FDA as well as OD designation by the European Medicines Agency (EMA) for the treatment of PG.

In September 2022, the Company submitted its application for emergency use authorization (EUA) of vilobelimab for the treatment of critically ill, intubated, mechanically ventilated COVID-19 patients with the FDA. The Company is in active dialogue with, and has received several requests for information from, the FDA, which the Company addressed. There is no set timeline for a decision from the FDA related to the EUA.

The Company will continue to interact closely with the FDA and will provide a timely update when appropriate. The Company´s management team will host investor and business meetings in San Francisco, CaliforniaJanuary 9 – 12 during JPM Week. Ulcerative pyoderma gangrenosum (PG) is a rare, non-infectious, neutrophilic dermatosis characterized by painful, necrolytic, cutaneous ulcers that can rapidly progress.

PG is considered an autoimmune disease of the skin, but the underlying cause of PG is not known in detail. PG lesions are histologically characterized by pronounced infiltration of neutrophils and activated neutrophils surrounding the ulcers are believed to be disease drivers. PG typically occurs in patients between 40 and 60 years of age, and PG patients often also suffer from other autoimmune disorders, such as inflammatory bowel diseases and rheumatoid arthritis.

There are no drugs currently approved for the treatment of PG in the US or in Europe, and there is no established standard of care based on controlled studies. Vilobelimab is a first-in-class monoclonal anti-human complement factor C5a antibody, which highly and effectively blocks the biological activity of C5a and demonstrates high selectivity towards its target in human blood. Thus, vilobelimab leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism, which is not the case for molecules blocking the cleavage of C5.

Vilobelimab has been demonstrated in pre-clinical studies to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key “amplifier” of this response. Vilobelimab is believed to be the first monoclonal anti-C5a antibody introduced into clinical development. Vilobelimab has been shown to be well tolerated within clinical trials in different disease settings.

Vilobelimab is currently being developed for various indications, including pyoderma gangrenosum (PG) and critical COVID-19. Vilobelimab is also in Phase II development for the treatment of patients suffering from cutaneous squamous cell carcinoma. The COVID-19 related work described herein is partly funded by the German Federal Government through grant number 16LW0113 (VILO-COVID).

All responsibility for the content of this work lies with InflaRx.