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Phase 2 N=255 Randomized Quadruple-blind Basic Science

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

Nonalcoholic Fatty Liver Disease · Nonalcoholic Steatohepatitis With Liver Fibrosis

Enrolled (actual)
255
Serious AEs
7.4%
Results posted
Mar 2025
Primary outcome: Primary: Mean Proportion of Participants Achieving Resolution of NASH Without Worsening/Improvement of Fibrosis by >=1 Stage Without Worsening of NASH/Both Based on Assessment by Sponsor-Identified Central Pathologist at Week 48:Bayesian Dose Response Model (BDRM) — 0.38; 0.45; 0.48; 0.50 Proportion of participants

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Placebo (Drug); PF-06865571 (Drug); PF-05221304 (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Pfizer
Primary completion
Jan 2024

Outcome Measures

OutcomeResultp-value
PRIMARY
Mean Proportion of Participants Achieving Resolution of NASH Without Worsening/Improvement of Fibrosis by >=1 Stage Without Worsening of NASH/Both Based on Assessment by Sponsor-Identified Central Pathologist at Week 48:Bayesian Dose Response Model (BDRM)
0.38; 0.45; 0.48; 0.50; 0.51
PRIMARY
Number of Participants Achieving Resolution of NASH Without Worsening or Improvement in Fibrosis by >= 1 Stage Without Worsening of NASH or Both Based on Assessment by Sponsor-Identified Central Pathologist at Week 48: Logistic Regression Model
13; 16; 25; 21; 23; 14
SECONDARY
Percent Change From Baseline in Liver Fat at Week 48: Bayesian Dose Response Model
-10.79; -36.76; -46.20; -51.33; -55.53
SECONDARY
Percent Change From Baseline in Liver Fat at Week 48: Pairwise Comparisons With Analysis of Covariance (ANCOVA)
1.41; -41.00; -42.53; -58.77; -67.76; -49.76
SECONDARY
Mean Proportion of Participants Achieving Resolution of NASH, Without Worsening of Fibrosis Based on Assessment by Sponsor-Identified Central Pathologist(s) at Week 48: Bayesian Dose Response Model
0.11; 0.32; 0.37; 0.40; 0.41
SECONDARY
Number of Participants Achieving Resolution of NASH, Without Worsening of Fibrosis Based on Assessment by Sponsor-Identified Central Pathologist(s) at Week 48: Pairwise Comparisons With Logistic Regression Model
3; 11; 22; 13; 22; 13
SECONDARY
Mean Proportion of Participants Achieving Improvement in Fibrosis by >=1 Stage, Without Worsening of NASH Based on Assessment by Sponsor-Identified Central Pathologist(s) at Week 48: Bayesian Dose Response Model
0.33; 0.28; 0.25; 0.24; 0.22
SECONDARY
Number of Participants Achieving Improvement in Fibrosis by >=1 Stage, Without Worsening of NASH Based on Assessment by Sponsor-Identified Central Pathologist(s) at Week 48: Pairwise Comparisons With Logistic Regression Model
12; 10; 10; 14; 13; 4
SECONDARY
Mean Proportion of Participants Achieving Improvement in Fibrosis by >=2 Stage, Without Worsening of NASH Based on Assessment by Sponsor-Identified Central Pathologist(s) at Week 48: Bayesian Dose Response Model
0.05; 0.08; 0.09; 0.09; 0.10
SECONDARY
Number of Participants Achieving Improvement in Fibrosis by >=2 Stage, Without Worsening of NASH Based on Assessment by Sponsor-Identified Central Pathologist(s) at Week 48: Pairwise Comparisons With Logistic Regression Model
1; 4; 3; 5; 7; 2
SECONDARY
Mean Proportion of Participants Achieving Improvement of >=2 Points in Total NAS, Without Progression of Fibrosis Based on Assessment by Sponsor-Identified Central Pathologist(s) at Week 48: Bayesian Dose Response Model
0.24; 0.42; 0.47; 0.49; 0.51
SECONDARY
Number of Participants Achieving Improvement of >=2 Points in Total NAS Without Progression of Fibrosis Based on Assessment by Sponsor-Identified Central Pathologist(s) at Week 48: Pairwise Comparisons With Logistic Regression Model
8; 13; 28; 21; 25; 12
SECONDARY
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
26; 25; 38; 30; 25; 26
SECONDARY
Number of Participants With Laboratory Test Abnormalities
31; 32; 46; 39; 34; 27
SECONDARY
Number of Participants With Clinically Significant Abnormalities in Vital Signs
0; 0; 0; 0; 0; 0
SECONDARY
Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECG) Parameters
0; 0; 0; 0; 0; 0

Summary

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).

Eligibility Criteria

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,
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04321031). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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