Kezar Life Sciences has announced plans to commence the Phase IIa PORTOLA clinical trial (KZR-616-208) of zetomipzomib to treat autoimmune hepatitis.
The move comes after the US Food and Drug Administration granted clearance for the Investigational New Drug (IND) application of Kezar Life Sciences for zetomipzomib.
The placebo-controlled, double-blind, randomised trial will analyse the safety and efficacy of zetomipzomib in AIH patients who are not responding well to the standard of care, or who have relapsed.
It is anticipated to enrol 24 subjects, who will be randomised into a 2:1 ratio to receive either zetomipzomib plus prednisone or a placebo plus prednisone for 24 weeks.
The trial will also have a protocol-directed steroid taper by week 14.
The proportion of subjects achieving a complete response as evaluated by the normalisation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, with a successful corticosteroid taper by week 24, will be the trial’s primary efficacy endpoint.
A selective immunoproteasome inhibitor, zetomipzomib has a wide-ranging treatment potential across various autoimmune diseases.
According to preclinical data, selective hindering of immunoproteasome leads to an extensive anti-inflammatory response in several autoimmune disease animal models while averting immunosuppression.
Findings from Phase I clinical trials of zetomipzomib also demonstrated a favourable safety and tolerability profile for severe, chronic autoimmune diseases.
Kezar Life Sciences chief medical officer Noreen Henig said: “Zetomipzomib is a unique small molecule with the potential to be a non-immunosuppressive, anti-inflammatory treatment for multiple autoimmune diseases.
“We plan to run PORTOLA, an early proof-of-concept study in parallel to our other development efforts, including a late-phase efficacy trial for patients with lupus nephritis and a potential programme in patients with systemic lupus erythematosus.”
A rare chronic ailment, AIH causes the immune system to attack the liver and leads to inflammation and tissue damage.
In June this year, the company reported positive data from the Phase II MISSION trial of zetomipzomib for active lupus nephritis.