A Study to Test Whether BI 3802876 is Tolerated in People With Compensated Liver Cirrhosis Due to Metabolic Dysfunction- Associated Steatohepatitis (MASH)

Official title

A Phase IIa Double-blind, Placebo-controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 3802876 in Participants With Compensated Cirrhosis Due to Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Overview

This study is open to adults with a type of confirmed liver condition called compensated cirrhosis due to Metabolic Dysfunction-Associated Steatohepatitis (MASH). The purpose of this study is to find out how well a study medicine called BI 3802876 is tolerated in people with this condition. The study looks at how different doses of BI 3802876 are handled by the body. BI 3802876 is being developed to improve liver health in people living with this liver condition. Participants are put in 3 different dose groups randomly, which means by chance. Participants within a group get BI 3802876 or placebo. Placebo looks like BI 3802876 but does not contain any medicine. Participants have more than twice the chance of receiving BI 3802876 than placebo. The study medicine is given as an infusion into a vein. Participants are in the study for about half a year. During this time, they visit the study site 12 times. At 2 visits, participants get the study medicine. Doctors collect information on any health problems and take blood samples to check how BI 3802876 is handled by the body. They compare results between the groups.

Interventions

• Drug BI 3802876
  BI 3802876
• Drug Placebo
  Placebo

Primary outcome measures

• Occurrence of any Adverse Events (AEs) [Time frame: up to 134 days]

Secondary outcome measures (3)

• Area under the concentration-time curve of the analyte in serum over the time interval from 0 extrapolated to infinity (AUC0-∞) [Time frame: up to 134 days]
• Maximum measured concentration of the analyte in serum (Cmax) [Time frame: up to 134 days]
• Relative change from baseline in N-terminal type III collagen propeptide (PRO-C3) at week 7 [Time frame: at baseline, at week 7]

Eligibility criteria

Inclusion criteria

• Male or female adults ≥18 to ≤75 years of age at the time of screening, and at least the legal age of consent in countries where it is > 18 years
• Patients meeting criteria for Child-Pugh category A without history of previous decompensation event
• Compensated Metabolic Dysfunction-Associated Steatohepatitis (MASH) cirrhosis diagnosed by 1 of the following:

• Biopsy (collected during screening or ≤ 5 years\* prior to screening) showing cirrhosis (fibrosis stage 4) with steatosis or steatohepatitis.
• Biopsy (collected during screening or ≤ 5 years\* prior to screening) showing cryptogenic cirrhosis.
• Biopsy showing steatosis or steatohepatitis prior to screening without confirmation of fibrosis stage 4, or current or previous imaging showing steatosis with no liver histology available must meet either one of the following inclusion criteria at screening:

• Vibration-controlled transient elastography (VCTE) ≥ 15 kilopascals (kPa) plus 1 of the following, Magnetic Resonance Enterography (MRE) ≥4.2 kPa, platelet count <150,000/μL or imaging techniques (computed tomography (CT) scan and/or Magnetic Resonance Imaging (MRI) and/or Ultrasound) suggestive of cirrhosis.
• VCTE measurement ≥ 20 kPa
• Enhanced Liver Fibrosis (ELF) score ≥ 10.2 \*If biopsy was collected > 365 days prior to screening either criteria a, b or c must be met Further inclusion criteria apply.

Exclusion criteria

• Patients with clinically significant portal hypertension defined by any of the following:

• VCTE ≥25 kPa if the platelets are ≥150,000/μL
• VCTE ≥20 kPa if platelets are <150,000/μL
• History of esophageal or gastric varices (Grade ≥1) on endoscopy
• ELF score ≥11.3
• Hepatic venous pressure gradient (HVPG) ≥10 mmHg
• Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis \[PBC\], primary sclerosing cholangitis \[PSC\], autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1- antitryspin deficiency
• Chronic viral hepatitis parameters that would be considered exclusionary for the participation in this trial are (hepatitis B and C testing will be done at screening visit):

• Hepatitis B virus (HBV): Past or present hepatitis B infection, including a positive hepatitis B surface antigen (HBsAg) and/or detectable HBV Deoxyribonucleic Acid (DNA).
• Hepatitis C virus (HCV): Past or present hepatitis C infection, including positive hepatitis C antibodies and/or detectable HCV ribonucleic acid (RNA).
• History of liver transplantation or patients listed for liver transplantation
• Suspicion, confirmed diagnosis, or history of Hepatocellular Carcinoma (HCC)
• Present or past evidence of decompensating events of liver cirrhosis
• Model for End-Stage Liver Disease (MELD) score > 12, unless due to therapeutic anti-coagulation
• History of significant alcohol consumption (defined as intake of > 210 g/week in males and > 140 g/week in females on average over a consecutive period of more than 3 months) within 1 year prior to screening
• International Normalized Ratio (INR) >1.3 unless due to therapeutic anticoagulants or laboratory error Further exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 26 centers

• Arizona Clinical Trials - Chandler — Chandler
• Southern California Research Center — Coronado
• Velocity Clinical Research, San Diego — La Mesa
• Kaiser Permanente - Los Angeles Medical Center — Los Angeles
• Catalina Research Institute, LLC — Montclair
• Peak Gastroenterology Associates — Colorado Springs
• Schiff Center Liver Diseases — Miami
• Panax Clinical Research — Miami Lakes
• … and 18 more centers

Canada · 1 center

• University of Alberta Hospital (University of Alberta) — Edmonton

Identifiers

NCT: NCT07325526 · 1517-0002 · 1111-1313-8064

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗