Evaluation of Efficacy, Safety and Tolerability of Aldafermin in a Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Study In Subjects With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis (ALPINE 2/3)

Phase 2

Completed

• Conditions: NASH - Nonalcoholic Steatohepatitis
• Interventions: Biological: NGM282; Other: Placebo

• Registration Number: NCT03912532
• Lead Sponsor: NGM Biopharmaceuticals, Inc

Brief Summary

This is a multi-center evaluation of NGM282 in a randomized, double-blind, placebo-controlled study administered for 24 weeks in participants with histologically confirmed NASH and F2/F3 Fibrosis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-09
• Study First Submitted QC: 2019-04-09
• Study First Posted: 2019-04-11
• Study Start: 2019-05-16
• Primary Completion: 2021-03-04
• Study Completion: 2021-03-29
• Status Verified: 2025-03
• Results First Submitted: 2025-03-07
• Results First Submitted QC: 2025-06-16
• Last Update Submitted: 2025-06-16
• Results First Posted: 2025-07-03
• Last Update Posted: 2025-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 171

Inclusion Criteria

1. Histologically confirmed NASH diagnosis as defined by the NASH CRN
2. Total liver fat content of ≥ 8% as measured by MRI-PDFF

Exclusion Criteria

1. Clinically significant acute or chronic liver disease of an etiology other than NASH
2. Evidence of drug-induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis
3. History or presence of cirrhosis (compensated or decompensated) as determined by histology and/or relevant medical complications and/or laboratory parameters
4. Prior or pending liver transplantation

Other protocol-defined inclusion/exclusion criteria could apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NGM282 Dose 1	NGM282	Administered by subcutaneous injection
NGM282 Dose 2	NGM282	Administered by subcutaneous injection
NGM282 Dose 3	NGM282	Administered by subcutaneous injection
Placebo	Placebo	Administered by subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Liver Fibrosis Response After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis	Baseline up to Week 24	Liver biopsies were collected at baseline and Week 24 and read by a central pathologist using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) criteria. Fibrosis stages of F0, F1, F2, F3 and F4 are defined by NASH CRN criteria with F0 (minimal score) indicating no fibrosis and F4 (maximal score) indicating liver cirrhosis. Liver fibrosis response was defined as an improvement in liver fibrosis \>=1 stage with no worsening of steatohepatitis on liver biopsy at Week 24 compared with baseline.
Number of Participants With Treatment-emergent Adverse Events After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis	Baseline up to Week 24	Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that commenced on or after the date and time of first study drug administration.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis	Baseline to Week 12, Week 24, and Week 30	Change from baseline in liver fat content was assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF). Negative values indicate an improvement in liver fat content.
Mean Percentage of Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis	Baseline, Week 12, Week 24, and Week 30	Mean percentage of liver fat content was assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF).
Number of Participants With Liver Fat Normalization and Response in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis	Baseline to Week 12, Week 24 and Week 30	Liver fat normalization (LFC; defined as \<5%) and response (LFC decrease \>=5% from baseline and LFC relative decrease \>=30% from baseline) were assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF). The responders were defined as participants with either normalization (\<5%) or response (decrease from baseline \>=5% or relative decrease from baseline \>=30%).

Trial Locations

Locations (4)

NGM Clinical Study Site; 🇵🇷 San Juan, Puerto Rico

NGM Clinical Study Site 814; 🇺🇸 Tucson, Arizona, United States

NGM Clinical Study Site 816; 🇺🇸 Tucson, Arizona, United States

NGM Clinical Study Site 845; 🇺🇸 Edinburg, Texas, United States