A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001)

Phase 2

Terminated

Brief Summary: This study will evaluate the effect of each dose of MK-3655 versus placebo on the percentage of individuals with NASH resolution without worsening of fibrosis after 52 weeks. The primary hypothesis of the study is that at least 1 dose of MK-3655 is superior to placebo with respect to the percentage of individuals with NASH resolution without worsening of fibrosis after 52 weeks.

Recruitment & Eligibility

Inclusion Criteria

Has histological confirmation of NASH
Is a male or female aged 18 years to 80 years (in Japan and Taiwan aged 20 to 80 years)
Has a body mass index (BMI) ≥25 kg/m^2 and ≤50 kg/m^2 and stable weight for the past 3 months
Has no history of Type 2 diabetes mellitus (T2DM) OR a history of T2DM controlled by diet or stable doses of antihyperglycemic agents (AHAs)
Contraceptive use by male participants should be consistent with local regulations.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and she is not a woman of child-bearing potential (WOCBP) OR she is a WOCBP and uses a contraceptive method that is highly effective during the intervention period and for at least 16 weeks after the last dose of study intervention.

Exclusion Criteria

Has presence of cirrhosis on liver biopsy
Has Type 1 diabetes
Has a history of malignancy, unless cancer free ≥5 years, or is under evaluation for active or suspected malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
Has a history of bariatric surgery ≤5 years before study participation
Has undergone a major surgical procedure ≤3 months before study participation or has major surgery planned during the study
Has a history or evidence of chronic liver disease other than NASH. Individuals with a history of Hepatitis B or C may be eligible for participation.
Has significant systemic or major illnesses other than liver disease, including recent events (≤6 months before study entry) of congestive heart failure, unstable coronary artery disease, arterial revascularization, pulmonary disease, renal failure, stroke, transient ischemic attack, or organ transplantation

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
MK-3655 50 mg	MK-3655	Following a 2-week placebo run-in, participants will receive MK-3655 50 mg by subcutaneous (SC) injection once every 4 weeks (Q4W) for 52 weeks.
MK-3655 100 mg	MK-3655	Following a 2-week placebo run-in, participants will receive MK-3655 100 mg by SC injection Q4W for 52 weeks.
Placebo	Placebo	Following a 2-week placebo run-in, participants will receive Placebo by SC injection Q4W for 52 weeks.
MK-3655 300 mg	MK-3655	Following a 2-week placebo run-in, participants will receive MK-3655 300 mg by SC injection Q4W for 52 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced an Adverse Event (AE)	Up to 64 weeks	An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.
Percentage of Participants Discontinuing Study Medication Due to an AE	Up to 52 weeks	An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.
Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 52 Weeks	Week 52	The NASH Clinical Research Network (CRN) scoring system evaluated by Blinded Independent Central Review (BICR) was used to assess treatment response. The NASH CRN scoring scales were: lobular inflammation score (0-3); hepatocyte ballooning score (0-2); steatosis score (0-3); and fibrosis score (0-4). NASH resolution was defined as a score of 0-1 for inflammation, 0 for ballooning, and any grade of steatosis.

Secondary Outcome Measures

Name	Time	Method
Mean Percent Relative Reduction From Baseline in Liver Fat Content (LFC) After 24 Weeks	Baseline and Week 24	LFC % was measured by Magnetic Resonance Imaging-Estimated Proton Density Fat Fraction (MRI-PDFF) and evaluated by BICR. MRI-PDFF is a highly accurate noninvasive measure of the proportion of fat content of a tissue.
Percentage of Participants With ≥2 Point Improvement in NAS With ≥1 Point Improvement in Inflammation or Ballooning Without Worsening of Fbrosis by Histology (Evaluated by BICR) After 52 Weeks	Week 52	Participants with ≥2 point improvement in the NAS with ≥1 point improvement in inflammation or ballooning without worsening of fibrosis were assessed with the NASH CRN scoring system (evaluated by BICR). The NAS was calculated as the unweighted sum of the scores and ranges from 0-8 (highest activity).
Percentage of Participants With ≥1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis Assessed With the NASH CRN Scoring System After 52 Weeks	Week 52	Participants were evaluated with the NASH CRN scoring system with BICR with ≥1 stage improvement in fibrosis without worsening of steatohepatitis defined as no increase in the ballooning, inflammation, or steatosis scores.

Locations (180): Adobe Clinical Research, LLC ( Site 2644)
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Tucson, Arizona, United States
Arizona Liver Health ( Site 9026)
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Tucson, Arizona, United States
Del Sol Research Management ( Site 2674)
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Tucson, Arizona, United States
Arkansas Gastroenterology - North Little Rock ( Site 9015)
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North Little Rock, Arkansas, United States
Hope Clinical Research, Inc. ( Site 2601)
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Canoga Park, California, United States
Velocity Clinical Research, Huntington Park ( Site 9022)
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Huntington Park, California, United States
UCSD - Altman Clinical and Translational Research Institute -UC San Diego NAFLD Research Center ( Si
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La Jolla, California, United States
Ruane Clinical Research Group, Inc ( Site 9014)
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Los Angeles, California, United States
Velocity Clinical Research, Westlake ( Site 9013)
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Los Angeles, California, United States
Catalina Research Institute, LLC ( Site 2643)
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Montclair, California, United States
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Adobe Clinical Research, LLC ( Site 2644)
🇺🇸Tucson, Arizona, United States