Clinical Trials

Inclusion Criteria:

• Male or female participants ≥ 18 years (or who are of legal age in countries where that is greater than 18 years) of age at time of consent.
• Diagnosis of MASH (NAS ≥ 4, with at least 1 point in inflammation and ballooning each) and fibrosis stage F2-F3 proven by a biopsy conducted during the screening period or by a historical biopsy conducted within the last 6 months prior to randomisation.
• Stable body weight defined as less than 5% self-reported change in body weight 3 months prior to the screening or during the period between the historical biopsy and randomisation, if a historical biopsy is used.  The participants will be randomised following screening parameters which needs to be met in consecutive order: AST > 20 U/L, liver stiffness measured by FibroScan® VCTE ≥ 7.5k Pa and FAST > 0.36 at screening) and liver fat fraction ≥ 8% measured by MRI-PDFF prior to scheduling the screening biopsy.
• Be willing to maintain a stable diet and physical activity levels throughout the entire trial.

Exclusion Criteria:

• Any of the following liver laboratory test abnormalities at screening:
  • Serum AST and/or ALT elevation ≥ 5x ULN;
  • Platelet count < 140 000/mm3 (< 140 GI/L);
  • Alkaline phosphatase > 2x ULN;
  • Abnormal synthetic liver function as defined by screening central laboratory evaluation:
    • Albumin below < 3.5 g/dL (35.0 g/L)
    • OR International normalised ratio (INR) of prothrombin time > 1.3 (unless participant is on anticoagulants)
    • OR total serum bilirubin concentration ≥1.5x ULN (participants with a documented history of Gilbert’s syndrome can be enrolled if the direct bilirubin is within normal reference range)
• Any history or evidence of acute or chronic liver disease other than MASH.
• Histologically documented liver cirrhosis (fibrosis stage F4), either at screening or in a historical biopsy.
• History of or current diagnosis of hepatocellular carcinoma.
• History of or planned liver transplant.
• Inability or unwillingness to undergo a liver biopsy at screening (if a suitable historical biopsy is unavailable for central review), or during trial conduct.
• History of portal hypertension or presence of decompensated liver disease (including hepatic encephalopathy, variceal bleeding, ascites, and spontaneous bacterial peritonitis)
• MELD score ≥ 12 due to liver disease Note: MELD of ≥ 12 must be the result of liver disease to be exclusionary, NOT isolated laboratory abnormalities such as elevated creatinine due to chronic kidney disease, INR abnormality secondary to anticoagulants or laboratory error, and bilirubin elevation due to Gilbert’s Syndrome.
• Treatment with any medication for the indication obesity within 3 months before screening biopsy or historical biopsy time point.
• HbA1c > 10% (> 86 mmol/mol) as measured by the central laboratory at screening.
• Impaired renal function, defined as eGFR 2x ULN as measured by the central laboratory at screening.
• Uncontrolled hypertension (mean SBP ≥ 160 mmHg and/or mean DBP ≥ 100 mmHg) at screening (at least two measurements 5 minutes apart).
• Major surgery (in the opinion of the investigator) performed within 3 months prior to screening or planned during the trial.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/06/2024. Questions regarding updates should be directed to the study team contact.