A Clinical Study of Efinopegdutide in Participants With Precirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-6024-013)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2b Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Efinopegdutide (MK-6024) in Adults With Precirrhotic Nonalcoholic Steatohepatitis

Conditions
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Non-alcoholic Fatty Liver Disease, Fatty Liver, Nonalcoholic, NAFLD, Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Efinopegdutide
* Drug: Semaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Efinopegdutide 4mg<br>Efinopegdutide administered by subcutaneous (SC) injection once weekly for 52 weeks in a dose-escalation regimen of 2 mg for 4 weeks and 4mg for 48 weeks. | Drug: Efinopegdutide<br>* Subcutaneous (SC) injection in dose-escalation regimens potentially including doses of 2 mg, 4 mg, 7 mg, and 10 mg<br>* Other names: JNJ-64565111;|
| Experimental: Efinopegdutide 7mg<br>Efinopegdutide administered by SC injection once weekly for 52 weeks in a dose-escalation regimen of 2 mg for 4 weeks, 4 mg for 4 weeks, and 7 mg for 44 weeks. | Drug: Efinopegdutide<br>* Subcutaneous (SC) injection in dose-escalation regimens potentially including doses of 2 mg, 4 mg, 7 mg, and 10 mg<br>* Other names: JNJ-64565111;|
| Experimental: Efinopegdutide 10mg<br>Efinopegdutide administered by SC injection once weekly for 52 weeks in a dose-escalation regimen of 2 mg for 4 weeks, 4 mg for 4 weeks, 7 mg for 4 weeks, and 10 mg for 40 weeks. | Drug: Efinopegdutide<br>* Subcutaneous (SC) injection in dose-escalation regimens potentially including doses of 2 mg, 4 mg, 7 mg, and 10 mg<br>* Other names: JNJ-64565111;|
| Placebo Comparator: Placebo<br>Placebo administered by SC injection once weekly for 52 weeks | Drug: Placebo<br>* SC injection of matching placebo<br>|
| Active Comparator: Semaglutide 2.4 mg<br>Semaglutide administered by SC injection once weekly for 52 weeks in a dose-escalation regimen of 0.25 mg for 4 weeks, 0.5 mg for 4 weeks, 1.0 mg for 4 weeks, 1.7 mg for 4 weeks, and 2.4 mg for 36 weeks. | Drug: Semaglutide<br>* SC injection in a dose-escalation regimen of 0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg<br>* Other names: Wegovy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis At 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. | Week 52 | 
| Percentage of Participants Who Experienced an Adverse Event (AE) | An adverse event (AE) is a health problem that happens or worsens during a study. | Up to 60 weeks | 
| Percentage of Participants Discontinuing Study Medication Due to an AE | An adverse event (AE) is a health problem that happens or worsens during a study. | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis At 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. | Week 52 | 
| Change from Baseline in Body Weight At 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. | Week 52 |