A Master Protocol for a Randomized, Controlled, Clinical Trial of Multiple Pharmacologic Agents in Adult Participants with Metabolic Dysfunction-Associated Steatotic Liver Disease Who Are at Increased Risk of Developing Major Adverse Liver Outcomes (Synergy-Outcomes)
Investigating Treatments for Fatty Liver Disease Related to Metabolic Issues
Raj Vuppalanchi, MD
Primary Investigator
Brief description of study
This multicenter, randomized, parallel-arm, double-blind, placebo-controlled Phase 3 umbrella- type master protocol aims to create a framework for simultaneously evaluating the safety and efficacy of multiple pharmacologic agents (interventions) for the treatment of high-risk metabolic dysfunction-associated steatotic liver disease.
Detailed description of study
Once enrolled in the MP, the participant will be randomized 1:1 to either ISA and then randomized 2:1 to study intervention or placebo. The MP study will continue until the number of events required for the final analysis for the primary composite endpoint is reached.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease
-
Age: 18 years - 100 years
-
Gender: All
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Informed Consent
1. Participants must be at least 18 years of age (or the legal age of consent according to
local regulations) at the time of signing the ICF and are capable of giving signed
informed consent, as described in Appendix 1, which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
Type of participant and disease characteristics
2. ELF score of ≥9 and ≤10.8 at screening (Visit 1).
3. VCTE-LSM ≥ 10 kPa and 4. Liver fat content ≥8% as determined by MRI-PDFF at Visit 2.
Note: Participants must meet inclusion criteria #2 and #3 before proceeding to the MRI
at Visit 2. Participants must meet MRI-PDFF criterion prior to inclusion in the study.
Sex assigned at birth and contraceptive/barrier requirements
5. Assigned male at birth/assigned female at birth.
Contraceptive use by participants should be consistent with local regulations regarding
the methods of contraception for those participating in clinical studies For the
contraception requirements of this protocol, see Section 10.4. Participants’ partners of
childbearing potential must also use contraception during the study. Participants must
not be pregnant, intending to be pregnant, breastfeeding, or intending to breastfeed.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply at screening or at
other specified visits:
Liver-related Medical Conditions
6. History of esophageal varices, gastric varices or varices needing treatment.
7. Clinical evidence of hepatic decompensation as defined by history of any of the
following
history of variceal hemorrhage
ascites, or
hepatic encephalopathy.
8. Histological diagnosis of cirrhosis by a previous liver biopsy.
9. Imaging evidence of cirrhosis with portal hypertension (for example, presence of
varices, splenomegaly, and ascites) or a hepatic mass suggestive of a potential
malignancy.
10. Evidence of other forms of chronic liver disease including but not limited to
alcoholic liver disease
Hepatitis B as defined by the presence of hepatitis B surface antigen
Hepatitis C as defined by the presence of hepatitis C virus RNA
Note: Participants who have been treated for hepatitis C and are confirmed
cured are eligible if they have a negative hepatitis C RNA test for at least
2 years prior to screening.
history of primary biliary cholangitis
primary sclerosing cholangitis
autoimmune liver disease
hemochromatosis
Wilson’s disease
Alpha-1-antitrypsin-related liver disease
current drug-induced liver disease as defined based on typical exposure and
history, and
any other type of liver disease other than MASLD.
11. Have abnormal liver values at screening
This study investigates metabolic dysfunction-associated steatotic liver disease (MASLD), a condition where fat builds up in the liver due to metabolic issues. The purpose of this study is to assess the safety and effectiveness of different investigational medications for adults with MASLD who are at high risk of serious liver problems. Participants in the study may also have type 2 diabetes mellitus (T2DM).
Participants will be randomly assigned to either receive the investigational medication or a placebo, which is an inactive substance that looks like the investigational medicine but does not contain any medicine. The study is designed to be double-blind, meaning neither participants nor researchers will know who receives the investigational medication or the placebo. The study will continue until enough data is collected for final analysis.
- Who can participate: Adults aged 18 and older with a specific ELF score within a defined range and a certain percentage of liver fat content, as determined by medical tests, can participate. Participants must not have certain liver-related conditions or other chronic liver diseases.
- Study details: Participants will be randomly assigned to receive either an investigational medication or a placebo. The study will be double-blind, meaning neither participants nor researchers will know who receives which treatment. Participants must follow specific contraceptive guidelines during the study, which include using effective birth control methods to prevent pregnancy.
