NASH - Nonalcoholic SteatohepatitisPhase 2NCT03912532

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)

A Phase 2 study testing NGM282 in people with NASH - Nonalcoholic Steatohepatitis, run by NGM Biopharmaceuticals, Inc at 37 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: NASH - Nonalcoholic Steatohepatitis
What is being tested?: NGM282
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 171 participants
Where: 37 sitesin 2 countries
Study dates: 16 May 2019to 29 Mar 2021
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

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

Who cannot join

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

Trial locations and contacts

37 sites in 2 countries.

Country

City, postcode or hospital

37 sites in 2 countries

United States36 sites

NGM Clinical Study Site
Ann Arbor, Michigan, 48109
NGM Clinical Study Site
Austin, Texas, 78757
NGM Clinical Study Site
Baltimore, Maryland, 21202
NGM Clinical Study Site
Baton Rouge, Louisiana, 70809
NGM Clinical Study Site
Boca Raton, Florida, 33434
NGM Clinical Study Site
Chandler, Arizona, 85224
NGM Clinical Study Site
Chicago, Illinois, 60611
NGM Clinical Study Site
Durham, North Carolina, 27708
NGM Clinical Study Site 845
Edinburg, Texas, 78539
NGM Clinical Study Site
Edinburg, Texas, 78539
NGM Clinical Study Site
Fayetteville, North Carolina, 28304
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
Hermitage, Tennessee, 37076
NGM Clinical Study Site
Houston, Texas, 77030
NGM Clinical Study Site
Jackson, Mississippi, 39216
NGM Clinical Study Site
Kansas City, Missouri, 64131
NGM Clinical Study Site
La Jolla, California, 92093
NGM Clinical Study Site
Lakewood Rch, Florida, 34211
NGM Clinical Study Site
Los Angeles, California, 90036
NGM Clinical Study Site
Los Angeles, California, 90057
NGM Clinical Study Site
New York, New York, 10029
NGM Clinical Study Site
North Little Rock, Arkansas, 72117
NGM Clinical Study Site
Port Orange, Florida, 32127
NGM Clinical Study Site
Poway, California, 92064
NGM Clinical Study Site
Rialto, California, 92377
NGM Clinical Study Site
Richmond, Virginia, 23226
NGM Clinical Study Site
Richmond, Virginia, 23298
NGM Clinical Study Site
San Antonio, Texas, 78229
NGM Clinical Study Site
San Antonio, Texas, 78233
NGM Clinical Study Site
Sarasota, Florida, 34240
NGM Clinical Study Site
St Louis, Missouri, 63104
NGM Clinical Study Site
The Villages, Florida, 32162
NGM Clinical Study Site 814
Tucson, Arizona, 85712
NGM Clinical Study Site 816
Tucson, Arizona, 85712

Other trials in United States

Puerto Rico1 site

NGM Clinical Study Site
San Juan

Other trials in Puerto Rico

About this study

Official title: A Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy, Safety, and Tolerability of Three Doses of NGM282 Administered for 24 Weeks for the Treatment of Histologically Confirmed Nonalcoholic Steatohepatitis (NASH)

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.

Conditions: NASH - Nonalcoholic Steatohepatitis
Being tested: NGM282, 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.

NGM282Biological
NGM282
PlaceboOther
Placebo for NGM282

Study groups in NCT03912532
Study group	Role	What they receive
NGM282 Dose 1	Experimental	Administered by subcutaneous injection Receives: Biological: NGM282
NGM282 Dose 2	Experimental	Administered by subcutaneous injection Receives: Biological: NGM282
NGM282 Dose 3	Experimental	Administered by subcutaneous injection Receives: Biological: NGM282
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.

Liver Fibrosis Response After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
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.
Measured: Baseline up to Week 24
Number of Participants With Treatment-emergent Adverse Events After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
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.
Measured: Baseline up to Week 24

Secondary outcomes (3)

Mean Percentage of Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
Mean percentage of liver fat content was assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF).
Measured: Baseline, Week 12, Week 24, and Week 30
Change From Baseline in Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
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.
Measured: Baseline to Week 12, Week 24, and Week 30
Number of Participants With Liver Fat Normalization and Response in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
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%).
Measured: Baseline to Week 12, Week 24 and Week 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 May 201929 Mar 2021

First posted11 Apr 2019
Study start16 May 2019
Primary completion4 Mar 2021
Study completion29 Mar 2021

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 NASH - Nonalcoholic SteatohepatitisStudies 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: 171 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03912532
Sponsor's protocol ID: 18-0108
Status last verified: Mar 2025
First submitted: 9 Apr 2019
Last updated: 3 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Harrison SA, Abdelmalek MF, Neff G, Gunn N, Guy CD, Alkhouri N, Bashir MR, Freilich B, Kohli A, Khazanchi A, Sheikh MY, Leibowitz M, Rinella ME, Siddiqui MS, Kipnes M, Moussa SE, Younes ZH, Bansal M, Baum SJ, Borg B, Ruane PJ, Thuluvath PJ, Gottwald M, Khan M, Chen C, Melchor-Khan L, Chang W, DePaoli AM, Ling L, Lieu HD. Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2022 Jul;7(7):603-616. doi: 10.1016/S2468-1253(22)00017-6. Epub 2022 Mar 21.
PubMed 35325622

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
NASH With Fibrosis, MASH With Fibrosis
Active, not recruitingPhase 1/2
A Study to Evaluate ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease or With Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH)
Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis
Active, not recruiting
Target of Suv420h1/2 in Hepatocytes
NAFLD
Active, not recruitingPhase 3
A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )
NASH - Nonalcoholic Steatohepatitis
Not yet recruitingPhase 2/3
Evaluating the Safety and Efficacy of Roflumilast in the Treatment of Nonalcoholic Fatty Liver Disease Patients
NAFLD (Nonalcoholic Fatty Liver Disease)

All NASH - Nonalcoholic Steatohepatitis trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy, Safety, and Tolerability of Three Doses of NGM282 Administered for 24 Weeks for the Treatment of Histologically Confirmed Nonalcoholic Steatohepatitis (NASH)
ClinicalTrials.gov ID: NCT03912532
Acronym / sponsor ID: 18-0108
Conditions: NASH - Nonalcoholic Steatohepatitis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 171 participants (actual)
Lead sponsor: NGM Biopharmaceuticals, IncIndustry (pharma, biotech, devices)
Study start: 16 May 2019 (actual)
Primary completion: 4 Mar 2021 (actual)
Study completion: 29 Mar 2021 (actual)
First posted: 11 Apr 2019 (actual)
Results: Posted 3 Jul 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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
NGM282 Dose 1	Experimental	Biological: NGM282Administered by subcutaneous injection
NGM282 Dose 2	Experimental	Biological: NGM282Administered by subcutaneous injection
NGM282 Dose 3	Experimental	Biological: NGM282Administered 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)

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

Key exclusion criteria (5 listed)

Clinically significant acute or chronic liver disease of an etiology other than NASH
Evidence of drug-induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis
History or presence of cirrhosis (compensated or decompensated) as determined by histology and/or relevant medical complications and/or laboratory parameters
Prior or pending liver transplantation
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
NGM282NGM282	Biological	NGM282 Dose 1, NGM282 Dose 2, NGM282 Dose 3
PlaceboPlacebo for NGM282	Other	Placebo

Primary outcome

Liver Fibrosis Response After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
Time frame: 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
Time frame: 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.

3 secondary outcomes

Mean Percentage of Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
Time frame: Baseline, Week 12, Week 24, and Week 30
Change From Baseline in Liver Fat Content in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
Time frame: Baseline to Week 12, Week 24, and Week 30
Number of Participants With Liver Fat Normalization and Response in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis
Time frame: Baseline to Week 12, Week 24 and Week 30

Results and safety

Results posted to the registry on 3 Jul 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aldafermin 0.3 mg	43	35
Aldafermin 1.0 mg	42	35
Aldafermin 3.0 mg	43	37
Placebo	43	36

Primary outcome: Liver Fibrosis Response After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis

Time frame: Baseline up to Week 24. Mean (Standard Error). Unit: score on a scale

Measure	Aldafermin 0.3 mg n = 43	Aldafermin 1.0 mg n = 42	Aldafermin 3.0 mg n = 43	Placebo n = 43
Value	0.24 (0.04)	0.25 (0.04)	0.27 (0.07)	0.23 (0.06)

Aldafermin 0.3 mg vs Aldafermin 1.0 mg vs Aldafermin 3.0 mg vs Placebo: p = 0.5534, Multiple comparison procedure step

Population analysed: Liver fibrosis response was assessed in the Intent-to-Treat Analysis Set.

Primary outcome: Number of Participants With Treatment-emergent Adverse Events After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis

Time frame: Baseline up to Week 24. Count of participants. Unit: Participants

Measure	Aldafermin 0.3 mg n = 43	Aldafermin 1.0 mg n = 41	Aldafermin 3.0 mg n = 43	Placebo n = 43
Any TEAE	30	34	38	36
Any TEAE, Grade 1	11	12	17	10
Any TEAE, Grade 2	16	18	19	24
Any TEAE, Grade 3	1	2	2	1
Any TEAE, Grade 4	2	1	0	1
Any TEAE, Grade 5	0	1	0	0
Any aldafermin-related TEAE	13	20	21	14
Any TEAE, not related to aldafermin	17	14	17	22

Population analysed: TEAEs were assessed in the Safety Analysis Set.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events (TEAEs) were collected from screening up to Week 30.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aldafermin 0.3 mg	1 of 43 (2.3%)	30 of 43 (69.8%)	0 of 43
Aldafermin 1.0 mg	4 of 41 (9.8%)	34 of 41 (82.9%)	1 of 41
Aldafermin 3.0 mg	1 of 43 (2.3%)	38 of 43 (88.4%)	0 of 43
Placebo	3 of 43 (7%)	36 of 43 (83.7%)	0 of 43

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35325622Harrison SA, Abdelmalek MF, Neff G, Gunn N, Guy CD, Alkhouri N, Bashir MR, Freilich B, Kohli A, Khazanchi A, Sheikh MY, Leibowitz M, Rinella ME, Siddiqui MS, Kipnes M, Moussa SE, Younes ZH, Bansal M, Baum SJ, Borg B, Ruane PJ, Thuluvath PJ, Gottwald M, Khan M, Chen C, Melchor-Khan L, Chang W, DePaoli AM, Ling L, Lieu HD. Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2022 Jul;7(7):603-616. doi: 10.1016/S2468-1253(22)00017-6. Epub 2022 Mar 21.
Individual participant dataSharing planned: No

Related trials for NASH - Nonalcoholic Steatohepatitis

RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
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A Study to Evaluate ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease or With Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH)
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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

37 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NGM282 in people with NASH - Nonalcoholic Steatohepatitis, run by NGM Biopharmaceuticals, Inc at 37 sites in 2 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 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Puerto Rico. 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 3 Jul 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?

Liver Fibrosis Response After Administration With Aldafermin in Participants With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis (time frame: Baseline up to Week 24). The study lists 2 primary outcomes in all. 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 NCT03912532, 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 3 Jul 2025.