Compensated CirrhosisPhase 2NCT04210245
Study of Aldafermin (NGM282) in Subjects With Compensated Cirrhosis (ALPINE 4)
A Phase 2 study testing aldafermin in people with Compensated Cirrhosis and Nonalcoholic Steatohepatitis, run by NGM Biopharmaceuticals, Inc at 49 sites in 9 countries.
Trial summary
A multi-center evaluation of aldafermin in a randomized, double-blind, placebo-controlled study in subjects with compensated cirrhosis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Compensated Cirrhosis, Nonalcoholic Steatohepatitis
- What is being tested?
- aldafermin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 49 sitesin 9 countries
- Study dates
- 23 Mar 2020to 23 Feb 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Liver biopsy consistent with NASH cirrhosis.
- Compensated cirrhosis due to NASH.
Who cannot join
- 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.
- Evidence of drug induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis.
- History of hepatic decompensation including variceal bleeding, ascites, or hepatic encephalopathy.
- Model of end stage liver disease (MELD) score >12.
- Other protocol-defined inclusion/exclusion criteria could apply.
Trial locations and contacts
49 sites in 9 countries.
49 sites in 9 countries
United States31 sites
NGM Clinical Study Site
Austin, Texas, 78746
NGM Clinical Study Site
Baltimore, Maryland, 21202
NGM Clinical Study Site
Boca Raton, Florida, 33434
NGM Clinical Study Site
Boston, Massachusetts, 02111
NGM Clinical Study Site
Boston, Massachusetts, 02114
NGM Clinical Study Site
Chicago, Illinois, 60611
NGM Clinical Study Site
Chicago, Illinois, 60637
NGM Clinical Study Site
Durham, North Carolina, 27710
NGM Clinical Study Site
Edinburg, Texas, 78229
NGM Clinical Study Site
Edinburg, Texas, 78539
NGM Clinical Study Site
Flowood, Mississippi, 39232
NGM Clinical Study Site
Fresno, California, 93720
NGM Clinical Study Site
Germantown, Tennessee, 38138
NGM Clinical Study Site
Glendale, Arizona, 85306
NGM Clinical Study Site 481
Houston, Texas, 77030
NGM Clinical Study Site 488
Jackson, Mississippi, 39216
NGM Clinical Study Site
Kansas City, Missouri, 64131
NGM Clinical Study Site
La Jolla, California, 92037
NGM Clinical Study Site
Los Angeles, California, 90057
NGM Clinical Study Site
Marietta, Georgia, 30060
NGM Clinical Study Site
Miami, Florida, 33136
NGM Clinical Study Site
North Little Rock, Arkansas, 72117
NGM Clinical Study Site
Panorama City, California, 91402
NGM Clinical Study Site
Rialto, California, 92377
NGM Clinical Study Site
Richmond, Virginia, 23249
NGM Clinical Study Site
Richmond, Virginia, 23298
NGM Clinical Study Site
San Antonio, Texas, 78215
NGM Clinical Study Site
San Antonio, Texas, 78229
NGM Clinical Study Site 482
Seattle, Washington, 98104
NGM Clinical Study Site 413
Tucson, Arizona, 85711
NGM Clinical Study Site 415
Tucson, Arizona, 85711
Australia8 sites
NGM Clinical Study Site
Adelaide, South Australia
NGM Clinical Study Site
Bedford Park, South Australia
NGM Clinical Study Site
Camperdown, New South Wales
NGM Clinical Study Site
Clayton, Victoria
NGM Clinical Study Site
Fitzroy, Victoria
NGM Clinical Study Site
Heidelberg, Victoria
NGM Clinical Study Site
Melbourne, Victoria
NGM Clinical Study Site
Westmead, New South Wales
France2 sites
NGM Clinical Study Site
Paris
NGM Clinical Study Site
Pessac, 33604
Germany2 sites
NGM Clinical Study Site
Leipzig, 04103
NGM Clinical Study Site
Leipzig
Poland2 sites
NGM Clinical Study Site 444
Wroclaw
NGM Clinical Study Site 446
Wroclaw
About this study
Official title: 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)
A multi-center evaluation of aldafermin in a randomized, double-blind, placebo-controlled study in subjects with compensated cirrhosis.
Read the detailed description
The study will compare multiple doses of aldafermin against placebo in a compensated NASH cirrhosis population for 48 weeks of treatment.
- Being tested
- aldafermin, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aldaferminBiological
aldafermin
PlaceboOther
Placebo for aldafermin
| Study group | Role | What they receive |
|---|---|---|
| Daily 0.3 mg dose | Experimental | Administered by subcutaneous injection Receives: Biological: aldafermin |
| Daily 1 mg dose | Experimental | Administered by subcutaneous injection Receives: Biological: aldafermin |
| Daily 3 mg dose | Experimental | Administered by subcutaneous injection Receives: Biological: aldafermin |
| Placebo | Placebo comparator | Administered by subcutaneous injection Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2019
- Study start23 Mar 2020
- Primary completion4 Jan 2023
- Study completion23 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Compensated CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- NGM Biopharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- NGM Study Director, Study director, NGM Biopharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04210245
- Sponsor's protocol ID
- 282-CC-207
- Status last verified
- Feb 2025
- First submitted
- 16 Dec 2019
- Last updated
- 26 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rinella ME, Lieu HD, Kowdley KV, Goodman ZD, Alkhouri N, Lawitz E, Ratziu V, Abdelmalek MF, Wong VW, Younes ZH, Sheikh AM, Brannan D, Freilich B, Membreno F, Sinclair M, Melchor-Khan L, Sanyal AJ, Ling L, Harrison SA. A randomized, double-blind, placebo-controlled trial of aldafermin in patients with NASH and compensated cirrhosis. Hepatology. 2024 Mar 1;79(3):674-689. doi: 10.1097/HEP.0000000000000607. Epub 2023 Sep 21.
PubMed 37732990
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04210245
- Acronym / sponsor ID
- 282-CC-207
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- NGM Biopharmaceuticals, IncIndustry (pharma, biotech, devices)
- Study start
- 23 Mar 2020 (actual)
- Primary completion
- 4 Jan 2023 (actual)
- Study completion
- 23 Feb 2023 (actual)
- First posted
- 24 Dec 2019 (actual)
- Results
- Posted 26 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Daily 0.3 mg dose | Experimental | Biological: aldaferminAdministered by subcutaneous injection |
| Daily 1 mg dose | Experimental | Biological: aldaferminAdministered by subcutaneous injection |
| Daily 3 mg dose | Experimental | Biological: aldaferminAdministered by subcutaneous injection |
| Placebo | Placebo comparator | Other: PlaceboAdministered by subcutaneous injection |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Liver biopsy consistent with NASH cirrhosis.
- Compensated cirrhosis due to NASH.
Key exclusion criteria (5 listed)
- 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.
- Evidence of drug induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis.
- History of hepatic decompensation including variceal bleeding, ascites, or hepatic encephalopathy.
- Model of end stage liver disease (MELD) score >12.
- Other protocol-defined inclusion/exclusion criteria could apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| aldaferminaldafermin | Biological | Daily 0.3 mg dose, Daily 1 mg dose, Daily 3 mg dose |
| PlaceboPlacebo for aldafermin | Other | Placebo |
Primary outcome
Change From Baseline in Enhanced Liver Fibrosis Score at Week 48
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37732990Rinella ME, Lieu HD, Kowdley KV, Goodman ZD, Alkhouri N, Lawitz E, Ratziu V, Abdelmalek MF, Wong VW, Younes ZH, Sheikh AM, Brannan D, Freilich B, Membreno F, Sinclair M, Melchor-Khan L, Sanyal AJ, Ling L, Harrison SA. A randomized, double-blind, placebo-controlled trial of aldafermin in patients with NASH and compensated cirrhosis. Hepatology. 2024 Mar 1;79(3):674-689. doi: 10.1097/HEP.0000000000000607. Epub 2023 Sep 21.
- Individual participant dataSharing planned: No
Related trials for Compensated Cirrhosis
RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
RecruitingObservational study
The Value of Spleen Thickness and Spleen Diameter for Gastroesophageal Varices Diagnosis in Compensated Cirrhosis
Liver Cirrhosis, Gastroesophageal Varices
RecruitingPhase 3
A Pivotal Clinical Study to Investigate the Safety and Efficacy of Efimosfermin Compared With Placebo in Adult Participants With Compensated Cirrhosis Due to Metabolic Dysfunction-associated Steatohepatitis (MASH)
Metabolic Dysfunction-associated Steatohepatitis
RecruitingPhase 3
A Study to Investigate Safety and Efficacy of Efimosfermin Compared With Placebo in Adult Participants With Compensated Cirrhosis Due to Metabolic Dysfunction-associated Steatohepatitis (MASH)
Metabolic Dysfunction-associated Steatohepatitis
RecruitingPhase 2
A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
NGM Study Director study director
NGM Biopharmaceuticals
49 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing aldafermin in people with Compensated Cirrhosis and Nonalcoholic Steatohepatitis, run by NGM Biopharmaceuticals, Inc at 49 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States, Australia, France, Germany, Poland and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Enhanced Liver Fibrosis Score at Week 48 (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04210245, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2025.