Metabolic Interventions to Resolve Non-alcoholic Steatohepatitis (NASH) With Fibrosis (MIRNA)

Study Overview
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Brief Summary
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The study aims to evaluate two, orally administered, investigational agents - PF-06865571 (DGAT2 inhibitor) and the coadministration of PF-06865571 with PF-05221304 (ACC inhibitor). This study is specifically designed to evaluate the effect of a range of doses of DGAT2i alone, and DGAT2i + ACCi, on resolution of NASH or improvement in liver fibrosis, as assessed histologically (via liver biopsy).

Official Title
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A PHASE 2, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PLACEBO-CONTROLLED, DOSE-RANGING, DOSE-FINDING, PARALLEL GROUP STUDY TO ASSESS EFFICACY AND SAFETY OF PF-06865571 (DGAT2I) ALONE AND WHEN COADMINISTERED WITH PF-05221304 (ACCI) IN ADULT PARTICIPANTS WITH BIOPSY-CONFIRMED NONALCOHOLIC STEATOHEPATITIS AND FIBROSIS STAGE 2 OR 3

Conditions
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Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis With Liver Fibrosis

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-06865571
* Drug: PF-05221304


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven NASH with either F2 or F3 fibrosis, per NASH CRN definition BMI >/= 22.5kg/m2 Exclusion Criteria: Evidence of other causes of liver disease such as Alcoholic steatohepatitis, (de)compensated cirrhosis, active viral hepatitis Any condition possibly affecting drug absorption -Unstable concomitant medical conditions, based on medical history or screening laboratory results including- unstable liver function tests, recent cardiovascular event(s) significant malignancies,

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: dose ranging, dose finding
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>participants will receive medication for 48 weeks | Drug: Placebo<br>* Tablet<br>|
| Experimental: PF-06865571 25 milligrams (mg) twice daily (BID)<br>participants will receive medication for 48 weeks | Drug: PF-06865571<br>* Tablet<br>|
| Experimental: PF-06865571 75 mg BID<br>participants will receive medication for 48 weeks | Drug: PF-06865571<br>* Tablet<br>|
| Experimental: PF-06865571 150 mg BID<br>participants will receive medication for 48 weeks | Drug: PF-06865571<br>* Tablet<br>|
| Experimental: PF-06865571 300 mg BID<br>participants will receive medication for 48 weeks | Drug: PF-06865571<br>* Tablet<br>|
| Experimental: PF-06865571 (150 mg BID) + PF-05221304 (5 mg BID)<br>participants will receive medication for 48 weeks | Drug: PF-06865571<br>* Tablet<br>Drug: PF-05221304<br>* Tablet<br>|
| Experimental: PF-06865771 (300 mg BID) + PF-05221304 (10 mg BID)<br>participants will receive medication for 48 weeks | Drug: PF-06865571<br>* Tablet<br>Drug: PF-05221304<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of NASH without worsening of fibrosis or improvement in fibrosis by 1>/= or both | Proportion of participants achieving resolution of NASH without worsening of fibrosis or improvement in fibrosis by ≥1 stage without worsening of NASH or both | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in liver fat | Percent change in liver fat (assessed via MRI-PDFF) | Week 48 | 
| Proportion of participants achieving Resolution of NASH, without worsening of fibrosis |  | Week 48 | 
| Proportion of participants achieving improvement in fibrosis by ≥1stage, without worsening of NASH |  | Week 48 | 
| Proportion of participants with Improvement in fibrosis by ≥2 stages, without worsening of NASH |  | Week 48 | 
| Proportion of participants with Improvement of ≥2 points in Total NASH |  | Week 48 | 
| Proportion of participants with a clinically significant change from baseline in vital signs |  | Baseline to Week 50 | 
| Proportion of participants with a clinically significant change from baseline in laboratory values |  | Baseline to Week 50 | 
| Proportion of participants with a clinically significant change from baseline in electrocardiograms (ECG) parameters |  | Baseline to Week 50 | 
| Proportion of participants with treatment-emergent adverse events (TEAE) |  | Baseline to Week 52 |