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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis.

Conditions
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Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: MK-3655
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-3655 Low Dose<br>MK-3655 low dose by subcutaneous (sc) injection once every 4 weeks (Q4W). | Drug: MK-3655<br>* MK-3655 low, middle, or high dose for injection<br>* Other names: NGM313;|
| Experimental: MK-3655 Middle Dose<br>MK-3655 middle dose by sc injection Q4W. | Drug: MK-3655<br>* MK-3655 low, middle, or high dose for injection<br>* Other names: NGM313;|
| Experimental: MK-3655 High Dose<br>MK-3655 high dose by sc injection Q4W. | Drug: MK-3655<br>* MK-3655 low, middle, or high dose for injection<br>* Other names: NGM313;|
| Placebo Comparator: Placebo<br>Matching placebo to MK-3655 by sc injection Q4W. | Drug: Placebo<br>* Matching placebo to MK-3655<br>|

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 After 52 Weeks | 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 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 is considered related to the medical treatment or procedure, that occurs during the course of the study. | Up to 56 weeks | 
| Percentage of Participants Discontinuing Study Medication Due to an AE | An adverse event (AE) is 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 is considered related to the medical treatment or procedure, that occurs during the course of the study. | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change from Baseline in Liver Fat Content (LFC) After 24 Weeks | LFC % is 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. | Baseline and Week 24 | 
| Percentage of Participants With ≥1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis Assessed With the NASH CRN Scoring System After 52 Weeks | Participants 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. | Week 52 | 
| Percentage of Participants With ≥2 Point Improvement in the Nonalcoholic Fatty Liver Disease Activity Score (NAS) Without Worsening of Fibrosis After 52 Weeks | Participants with ≥2 point improvement in the NAS with ≥1 point improvement in inflammation or ballooning without worsening of fibrosis assessed with the NASH CRN scoring system (evaluated by BICR). The NAS is calculated as the unweighted sum of the scores and ranges from 0-8 (highest activity). | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic fatty liver disease