AFFIRM: A randomized, double-blind, placebo-controlled study to assess the efficacy of Seladelpar on clinical outcomes in patients with primary biliary cholangitis (PBC) and compensated cirrhosis

Zusammenfassung der Studie

This study investigates how Seladelpar (the study drug) improves clinical outcomes in patients with primary biliary cholangitis (PBC) and compensated cirrhosis (In cirrhosis, the tissue hardens and shrinks.) and assesses the safety of Seladelpar. This is done by examining changes in overall health, symptom severity, and the progression of PBC. Seladelpar is an investigational drug. This is a randomized, double-blind, placebo-controlled study. Randomized means that you will be selected at random (like flipping a coin) to receive either the study drug or placebo. The placebo looks like the study drug but contains no active ingredient. Double-blind means that neither you nor your study doctor will know whether you are taking the study drug or placebo. Participants must have PBC in connection with liver cirrhosis, which can be classified according to the so-called Child Pugh (CP) criteria. Only individuals with PBC and cirrhosis of severity CP-A or CP-B will be included in this study. Participants will be randomly assigned to either the study drug or the corresponding placebo capsules. The probability of receiving the study drug is about two-thirds (67%), and the probability of receiving placebo is about one-third (33%). This study is an international study. This means there are approximately 5 participants in Switzerland and a total of 318 participants worldwide, at about 250 medical centers globally. Your participation in this study will last approximately 38 months (about 3 years and 2 months).

(BASEC)

Untersuchte Intervention

Participants with cirrhosis in CP stage A will receive 10 mg of the study drug or placebo. Participants with cirrhosis in CP stage B will receive 5 mg of the study drug or placebo. You will take the assigned treatment orally (by mouth) once daily, always at approximately the same time of day. Neither you nor your study doctor will know whether you are receiving the study drug or placebo. If the CP stage of your cirrhosis changes from CP-A to CP-B during the study, your dose will be adjusted: from 10 mg Seladelpar or corresponding placebo to 5 mg Seladelpar or corresponding placebo.

Seladelpar (MBX-8025 and previously RWJ-800025) is an oral, effective, and selective PPARδ agonist (i.e., a Delpar) that targets various cell types in the liver and leads to anticholestatic (against the backlog of bile fluid), anti-inflammatory, anti-itching, and antifibrotic (against fibrosis/scarring) effects in animal studies and human studies. Seladelpar is being developed for the treatment of primary biliary cholangitis (PBC), including itching (pruritus), a burdensome symptom for many PBC patients.

(BASEC)

Untersuchte Krankheit(en)

Primary biliary cholangitis (PBC) Primary biliary cholangitis (PBC) begins (= primary) with inflammation of the small bile ducts in the liver. The bile ducts are small channels (= ducts) that carry bile from the liver to the gallbladder and then to the small intestine. The inflammation obstructs the flow of bile from the liver, causing bile fluid to accumulate there. The bile ducts are increasingly damaged by this backlog and chronic inflammation. Over time, a network of scar tissue develops throughout the liver (= fibrosis). The scar tissue increasingly replaces liver tissue. This destroys the internal structure of the liver and can lead to cirrhosis. In cirrhosis, the tissue hardens and shrinks. The organ is destroyed.

(BASEC)

Sponsor

Gilead Sciences, Inc., Foster City, USA Gilead Sciences Switzerland Sàrl, Zug

(BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Zürich

(BASEC)

Datum der Bewilligung durch die Ethikkommission

13.06.2025

(BASEC)

Ergebnisse der Studie