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

Evaluation of Efficacy, Safety and Tolerability of NGM282 (Aldafermin) in a Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Study in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (ALPINE 4)

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04210245
Enrollment
160
Registered
2019-12-24
Start date
2020-03-23
Completion date
2023-02-23
Last updated
2025-03-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Compensated Cirrhosis, Nonalcoholic Steatohepatitis

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.

Interventions

BIOLOGICALaldafermin

aldafermin

OTHERPlacebo

Placebo for aldafermin

Sponsors

NGM Biopharmaceuticals, Inc
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No

Inclusion criteria

Key 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/

Design outcomes

Primary

MeasureTime frameDescription
Change From Baseline in Enhanced Liver Fibrosis Score at Week 4848 weeksEnhanced 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.

Countries

Australia, Belgium, France, Germany, Hong Kong, Poland, Puerto Rico, United Kingdom, United States

Participant flow

Participants by arm

ArmCount
Daily 0.3 mg Dose
Administered by subcutaneous injection daily for 48 weeks
7
Daily 1 mg Dose
Administered by subcutaneous injection daily for 48 weeks
42
Daily 3 mg Dose
Administered by subcutaneous injection daily for 48 weeks
55
Placebo
Administered by subcutaneous injection daily for 48 weeks
56
Total160

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Overall Study1 due to life stressors and injection site discomfort and 1 subject started prohibited medication0002
Overall StudyAdverse Event0360
Overall StudyLost to Follow-up0111
Overall StudyWithdrawal by Subject0144

Baseline characteristics

CharacteristicDaily 0.3 mg DoseDaily 1 mg DoseDaily 3 mg DosePlaceboTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
2 Participants18 Participants18 Participants11 Participants49 Participants
Age, Categorical
Between 18 and 65 years
5 Participants24 Participants37 Participants45 Participants111 Participants
Age, Continuous59.7 years
STANDARD_DEVIATION 6.78
61.3 years
STANDARD_DEVIATION 7.57
59.6 years
STANDARD_DEVIATION 8.72
58.3 years
STANDARD_DEVIATION 8.11
59.6 years
STANDARD_DEVIATION 8.15
BMI32.768 kg/m^2
STANDARD_DEVIATION 3.2236
35.979 kg/m^2
STANDARD_DEVIATION 6.3231
34.265 kg/m^2
STANDARD_DEVIATION 6.7146
34.757 kg/m^2
STANDARD_DEVIATION 7.1164
34.822 kg/m^2
STANDARD_DEVIATION 6.6468
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants8 Participants12 Participants18 Participants40 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
4 Participants33 Participants43 Participants38 Participants118 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants1 Participants0 Participants0 Participants2 Participants
Height164.3 centimeter
STANDARD_DEVIATION 11.35
167.5 centimeter
STANDARD_DEVIATION 11.23
166.2 centimeter
STANDARD_DEVIATION 10.02
163.9 centimeter
STANDARD_DEVIATION 8.89
165.7 centimeter
STANDARD_DEVIATION 10.05
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants1 Participants1 Participants0 Participants2 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants4 Participants5 Participants10 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants2 Participants1 Participants3 Participants
Race (NIH/OMB)
More than one race
0 Participants2 Participants1 Participants4 Participants7 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
7 Participants38 Participants47 Participants46 Participants138 Participants
Sex: Female, Male
Female
5 Participants23 Participants36 Participants39 Participants103 Participants
Sex: Female, Male
Male
2 Participants19 Participants19 Participants17 Participants57 Participants
Weight88.19 kilogram
STANDARD_DEVIATION 9.68
101.47 kilogram
STANDARD_DEVIATION 22.24
95.27 kilogram
STANDARD_DEVIATION 22.407
93.43 kilogram
STANDARD_DEVIATION 19.906
95.95 kilogram
STANDARD_DEVIATION 21.255

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
0 / 71 / 420 / 550 / 56
other
Total, other adverse events
5 / 740 / 4252 / 5549 / 56
serious
Total, serious adverse events
0 / 711 / 425 / 553 / 56

Outcome results

Primary

Change From Baseline in Enhanced Liver Fibrosis Score at Week 48

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.

Time frame: 48 weeks

Population: Enrollment to the 0.3 mg dose treatment arm was terminated during the study.

ArmMeasureValue (MEAN)Dispersion
Daily 0.3 mg DoseChange From Baseline in Enhanced Liver Fibrosis Score at Week 48-0.071 score on a scaleStandard Deviation 0.7214
Daily 1 mg DoseChange From Baseline in Enhanced Liver Fibrosis Score at Week 480.125 score on a scaleStandard Deviation 0.6938
Daily 3 mg DoseChange From Baseline in Enhanced Liver Fibrosis Score at Week 48-0.213 score on a scaleStandard Deviation 0.6145
PlaceboChange From Baseline in Enhanced Liver Fibrosis Score at Week 480.263 score on a scaleStandard Deviation 0.5767

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026