Study of Aldafermin (NGM282) in Subjects With Compensated Cirrhosis (ALPINE 4)

Phase 2

Completed

• Conditions: Compensated Cirrhosis; Nonalcoholic Steatohepatitis
• Interventions: Biological: aldafermin; Other: Placebo

• Registration Number: NCT04210245
• Lead Sponsor: NGM Biopharmaceuticals, Inc

Brief Summary

A multi-center evaluation of aldafermin in a randomized, double-blind, placebo-controlled study in subjects with compensated cirrhosis.

Detailed Description

The study will compare multiple doses of aldafermin against placebo in a compensated NASH cirrhosis population for 48 weeks of treatment.

Study Timeline

• Study First Submitted: 2019-12-16
• Study First Submitted QC: 2019-12-20
• Study First Posted: 2019-12-24
• Study Start: 2020-03-23
• Primary Completion: 2023-01-04
• Study Completion: 2023-02-23
• Results First Submitted: 2024-11-14
• Status Verified: 2025-02
• Results First Submitted QC: 2025-03-24
• Last Update Submitted: 2025-03-24
• Results First Posted: 2025-03-26
• Last Update Posted: 2025-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. Liver biopsy consistent with NASH cirrhosis.
2. Compensated cirrhosis due to NASH.

Key

Exclusion Criteria

1. Other causes of liver disease including but not limited to alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders, primary biliary cirrhosis, drug-induced hepatotoxicity, Wilson's disease, hemochromatosis, and alpha-1-anti-trypsin definition based on medical history and/or centralized read of liver histology.
2. Evidence of drug induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis.
3. History of hepatic decompensation including variceal bleeding, ascites, or hepatic encephalopathy.
4. Model of end stage liver disease (MELD) score >12.

Other protocol-defined inclusion/exclusion criteria could apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Daily 0.3 mg dose	aldafermin	Administered by subcutaneous injection
Placebo	Placebo	Administered by subcutaneous injection
Daily 3 mg dose	aldafermin	Administered by subcutaneous injection
Daily 1 mg dose	aldafermin	Administered by subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Enhanced Liver Fibrosis Score at Week 48	48 weeks	Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test derived from the measurement of hyaluronic acid (HA), amino terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloprotease 1 (TIMP1) using a proprietary algorithm (Siemens). ELF score is a laboratory test, is unitless, and is used as a continuous variable. The minimal ELF score is zero, the maximal ELF score is unknown. The higher the ELF score, the worse the disease outcome.; ELF is a score on a scale of severity assessment against biopsy-proven fibrosis. A score of \<7.7 is none to mild, \> 7.7-9.8 is moderate, \> 9.8 is severe.

Trial Locations

Locations (9)

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

NGM Clinical Study Site 413; 🇺🇸 Tucson, Arizona, United States

NGM Clinical Study Site 415; 🇺🇸 Tucson, Arizona, United States

NGM Clinical Study Site 488; 🇺🇸 Jackson, Mississippi, United States

NGM Clinical Study Site 481; 🇺🇸 Houston, Texas, United States

NGM Clinical Study Site 482; 🇺🇸 Seattle, Washington, United States

NGM Clinical Study Site 444; 🇵🇱 Wroclaw, Poland

NGM Clinical Study Site 446; 🇵🇱 Wroclaw, Poland

NGM Clinical Study Site 466; 🇬🇧 London, United Kingdom