Fatty Liver, Nonalcoholic, NAFLD, Non-alcoholic Fatty Liver Disease, Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis
Conditions
Brief summary
The purpose of this study is to learn how well efinopegdutide works compared to placebo in people who have non-alcoholic steatohepatitis (NASH). Researchers will also learn about the safety and benefit of efinopegdutide and how well people tolerate the medicine. The main goal of the study is to compare how many people taking efinopegdutide or placebo stop showing evidence of NASH without liver scarring getting worse.
Interventions
DRUGEfinopegdutide
Subcutaneous (SC) injection in dose-escalation regimens potentially including doses of 2 mg, 4 mg, 7 mg, and 10 mg
DRUGSemaglutide
SC injection in a dose-escalation regimen of 0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg
DRUGPlacebo
SC injection of matching placebo
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Histological confirmation of NASH, defined as NAFLD Activity Score (NAS) ≥4 with a score ≥1 point in each component (steatosis, ballooning, and lobular inflammation) AND NASH clinical research network (CRN) fibrosis score of Stage 2 or 3 * No history of Type 2 diabetes mellitus (T2DM) OR a history of T2DM with an A1C ≤9% that is controlled by diet or stable doses of antihyperglycemic agents (AHAs) * Participants in South Korea are eligible between the ages of 19 to 80 years of age (inclusive)
Exclusion criteria
* History of liver disease other than NASH * History or evidence of cirrhosis * History of pancreatitis * History of Type 1 diabetes mellitus (T1DM), diabetic ketoacidosis, or diabetes secondary to pancreatectomy * History of a bariatric surgical procedure ≤5 years before study entry, or a known clinically significant gastric emptying abnormality * Has significant systemic or major illnesses, including recent events (≤6 months before study entry) of congestive heart failure, unstable angina, myocardial infarction, arterial revascularization, stroke, or transient ischemic attack
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis At Week 52 | Week 52 | The NASH Clinical Research Network (CRN) scoring system evaluated by Blinded Independent Central Review (BICR) is used to assess treatment response. The NASH CRN scoring scales are: lobular inflammation score (0-3); hepatocyte ballooning score (0-2); steatosis score (0-3); and fibrosis score (0-4). NASH resolution is defined as a score of 0-1 for inflammation, 0 for ballooning, and any grade of steatosis. |
| Percentage of Participants Who Experienced an Adverse Event (AE) | Up to 60 weeks | An adverse event (AE) is a health problem that happens or worsens during a study. |
| Percentage of Participants Discontinuing Study Medication Due to an AE | Up to 52 weeks | An adverse event (AE) is a health problem that happens or worsens during a study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis At Week 52 | Week 52 | Participants will be assessed using the NASH CRN scoring system evaluated by BICR for ≥1-stage improvement in fibrosis without worsening of steatohepatitis. Fibrosis is scored from stage 0 to 4 where 0 = None, 1=Perisinusoidal OR periportal, 2=Perisinusoidal AND portal/periportal, 3= Bridging fibrosis, 4=Cirrhosis. No worsening of steatohepatitis is defined as no increase in the ballooning, inflammation, or steatosis scores. |
| Change from Baseline in Body Weight At Week 52 | Week 52 | Body weight (kg) will be measured using a standardized, digital scale. The percent change from baseline in body weight after 52 weeks will be reported. |
Countries
Austria, Belgium, Canada, Chile, China, Colombia, Czechia, France, Hong Kong, Hungary, Israel, Italy, Japan, Mexico, Peru, Portugal, Puerto Rico, Singapore, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed