InflaRx N.V. announced that the first patient has been dosed in its Phase III study investigating the efficacy and safety of vilobelimab in ulcerative PG, a rare neutrophilic and inflammatory skin disease characterized by destructive, painful cutaneous ulcers. The Phase III clinical study is designed to enroll patients worldwide, including countries such as the U.S., countries in Europe, and Australia. The multi-national, randomized, double-blind, placebo-controlled trial has two arms: one arm receiving vilobelimab (2400mg every other week) plus a low dose of corticosteroids and another arm receiving 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 is complete closure of the target ulcer at any time up to 26 weeks after initiation of treatment. 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), which is planned upon enrollment of approximately 30 patients, divided equally between the two aforementioned arms of the study.

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 will then determine whether the trial sample size will be adapted or whether the trial should be stopped due to futility. The enrollment period is projected to last at least two years, and its overall period will depend on the total trial size after sample size adaptation. The Company has received Fast Track and Orphan Drug (OD) designations by the U.S. Food and Drug Administration (FDA), as well as OD designation by the European Medicines Agency (EMA) for the treatment of PG.

Ulcerative PG is a rare, non-infectious, neutrophilic dermatosis recurrent skin disorder 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 the ages of 40 and 60, and PG patients often also suffer from other autoimmune disorders, such as inflammatory bowel disease and rheumatoid arthritis. There are currently no approved drugs for the treatment of PG in the U.S. 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 of the innate immune system, which is not the case for molecules blocking C5. In pre-clinical studies, vilobelimab has been shown to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key ?amplifier? of this response.

Gohibic (vilobelimab) has been granted an Emergency Use Authorization (EUA) in the U.S. for the treatment of COVID-19 in hospitalized adults when initiated within 48 hours of receiving invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). A Marketing Authorization Application (MAA) for the treatment of adult patients with SARS-CoV-2 induced septic acute respiratory distress syndrome receiving IMV or ECMO is currently under review by the European Committee for Medicinal Products for Human Use. In addition to development in COVID-19, vilobelimab is being developed for other debilitating or life-threatening inflammatory indications, including pyoderma gangrenosum.