NCT04321031|CompletedPhase 2ResultsDMCFDA Drug

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

MIRNA

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

Pfizer ClinicalTrials.gov

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2 other identifiers

C25410132019-004775-39

Study Type

interventional

Target

256

Locations

12 countries

Sites

291

Timeline

RegisteredMar 2020

StartedJun 2020

CompletionFeb 2024

Brief 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).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

256

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Jun 2020

Typical duration for phase_2

Geographic Reach

12 countries

291 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.7 years study duration

First Submitted

Initial submission to the registry

March 23, 2020

Completed

2 days until next milestone

First Posted

Study publicly available on registry

March 25, 2020

Completed

3 months until next milestone

Study Start

First participant enrolled

June 15, 2020

Completed

3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 23, 2024

Completed

29 days until next milestone

Study Completion

Last participant's last visit for all outcomes

February 21, 2024

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

March 21, 2025

Completed

Last Updated

March 21, 2025

Status Verified

March 1, 2025

Enrollment Period

3.6 years

First QC Date

March 23, 2020

Results QC Date

January 17, 2025

Last Update Submit

March 4, 2025

Conditions

Nonalcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis With Liver Fibrosis

Outcome Measures

Primary Outcomes (2)

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)
NASH resolution: disappearance of ballooning (Nonalcoholic Fatty Liver Disease \[NAFLD\] Activity Score \[NAS\] ballooning score=0;0=no ballooning,1=few balloon cells,2=many cells with prominent ballooning; higher scores(HS)=more disease activity \[DA\]),residual/no lobular inflammation(NAS lobular inflammation score 0/1,0=no foci,1= \<2 foci, 2=2-4 foci,3= \>4 foci; HS=more DA),NAS steatosis score 0,1,2,3; 0= \<5% hepatocytes involved (HI),1=5-33% HI ,2= 34-66% HI, 3= \>66% HI; HS=more DA. No worsening of fibrosis: no change/decrease of at least 1 stage in Brunt-Kleiner scale (BKS) compared to baseline (CTB). Improvement in fibrosis by \>=1 stage: decrease of at least 1 stage in BKS CTB. No worsening of NASH: no change/increase in NAS for ballooning, inflammation, steatosis CTB. BDRM utilized to characterize dose response across BID treatment groups, estimate posterior mean proportion (\& 90% credible interval \[CI\], indicated as 'confidence interval' below) for placebo and each BID dose studied.
Week 48
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
Resolution of NASH: disappearance of ballooning (NAS ballooning score= 0; where 0= no ballooning, 1= few balloon cells, 2= many cells with prominent ballooning; higher scores= more disease activity), residual or no lobular inflammation (NAS lobular inflammation score 0 or 1, where 0= no foci, 1= \<2 foci, 2= 2-4 foci, 3= \>4 foci; higher scores= more disease activity), NAS steatosis score 0, 1, 2, or 3, where 0= \<5% hepatocytes involved, 1= 5-33% hepatocytes involved, 2= 34-66% hepatocytes involved, 3= \>66% hepatocytes involved; higher scores= more disease activity. No worsening of fibrosis: no change or decrease of at least 1 stage in BKS compared to baseline. Improvement in fibrosis by \>=1 stage: decrease of at least 1 stage in BKS compared to baseline. No worsening of NASH: no change or increase in NAS for ballooning, inflammation, steatosis compared to baseline.
Week 48

Secondary Outcomes (14)

Percent Change From Baseline in Liver Fat at Week 48: Bayesian Dose Response Model
Baseline, Week 48
Percent Change From Baseline in Liver Fat at Week 48: Pairwise Comparisons With Analysis of Covariance (ANCOVA)
Baseline, Week 48
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
Week 48
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
Week 48
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
Week 48
+9 more secondary outcomes