Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)Phase 2NCT07527910
A Phase 2a Study of ALN-PNP With and Without a GLP1R Agonist in Adult Patients With Homozygous PNPLA3-Related MASLD
A Phase 2 study testing ALN-PNP and Tirzepatide in people with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), run by Regeneron Pharmaceuticals at 9 sites in United States.
Trial summary
This study will test a study drug called ALN-PNP with and without another drug that is used for controlling blood sugar, appetite, and weight (for example, tirzepatide), to see if it can help treat MASLD, also known as fatty liver disease. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
- What is being tested?
- ALN-PNP and Tirzepatide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 204 participants
- Where
- 9 sitesUnited States
- Study dates
- 22 May 2026to 15 Mar 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Part A and Part B:
- Homozygous for the PNPLA3 p.I148M genotype
- Liver fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥15% at visit 3
- Has a Body Mass Index (BMI) ≥30 to <45 kg/m^2 at visit 2
- Part A: To be eligible for randomization on study day 1:
- Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3 × Upper Limit of Normal (ULN) as described in the protocol
- On a stable dose of tirzepatide at randomization (≥5 mg weekly)
Who cannot join
- Evidence or diagnosis of portal hypertension or cirrhosis from any cause, including cirrhosis due to MASH, as determined by the investigator, based on medical history, clinical assessment, imaging, and/or liver biopsy
- Known chronic liver disease other than MASLD, as determined by the investigator, as defined in the protocol
- Contraindications to MRI examinations, including but not limited to persons with MRI-incompatible cardiac pacemaker and implants made of metal, severe claustrophobia, size restrictions
- Any contraindication listed in the Zepbound United States Prescribing Information (USPI), as defined in the protocol
- NOTE: Other protocol-defined inclusion/exclusion criteria apply.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
United States9 sites, 9 recruiting
- Recruiting
American Research Corporation
Austin, Texas, 78757
- Recruiting
Southern California Research Center
Coronado, California, 92118
- Recruiting
Advanced Medical Trials
Georgetown, Texas, 78628
- Recruiting
Health Awareness, Inc
Jupiter, Florida, 33458
- Recruiting
Tandem Clinical Research, Plaza II
Metairie, Louisiana, 70006
- Recruiting
Evolution Clinical Trials
Miami, Florida, 33122
- Recruiting
California Liver Research Institute
Pasadena, California, 91105
- Recruiting
American Research Corporation at The Texas Liver Institute
San Antonio, Texas, 78215
- Recruiting
Arizona Liver Health - Tucson
Tucson, Arizona, 85712
About this study
Official title: A Two-Part, Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study of ALN-PNP With and Without a GLP1R Agonist in Adults With Homozygous PNPLA3-Related Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
This study will test a study drug called ALN-PNP with and without another drug that is used for controlling blood sugar, appetite, and weight (for example, tirzepatide), to see if it can help treat MASLD, also known as fatty liver disease. ALN-PNP reduces the amount of Patatin-like phospholipase domain-containing protein 3 (PNPLA3), a protein that liver cells make, which may help decrease liver fat if there is an abnormal PNPLA3 protein.
The goal of this study is to understand the effect of ALN-PNP with or without tirzepatide on reducing liver fat.
Read more
The study is looking at:
- How well ALN-PNP with and without tirzepatide works
- What side effects ALN-PNP might cause
- How much ALN-PNP is in the blood at different times
- How the body and the liver change after having ALN-PNP, which can help researchers understand why ALN-PNP works better in some people than others
- Being tested
- ALN-PNP, Tirzepatide, Placebo
- Keywords
- Homozygous PNPLA3-Related MASLD, Fatty Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis (MASH), Non-Alcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
- 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.
ALN-PNPDrug
Administered per the protocol
TirzepatideDrug
Also called Zepbound®
Administered per the protocol
PlaceboDrug
Administered per the protocol Placebo matching ALN-PNP
| Study group | Role | What they receive |
|---|---|---|
| Part A: A1 | Experimental | Not described Receives: Drug: ALN-PNP; Drug: Tirzepatide |
| Part A: A2 | Experimental | Not described Receives: Drug: Tirzepatide; Drug: Placebo |
| Part B: B1 | Experimental | Not described Receives: Drug: ALN-PNP; Drug: Tirzepatide |
| Part B: B2 | Experimental | Not described Receives: Drug: Tirzepatide; Drug: Placebo |
| Part B: B3 | Experimental | Not described Receives: Drug: ALN-PNP |
| Part B: B4 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in liver fat
Part A
Measured: From baseline at week 24
Percent change in liver fat
Part B
Measured: From baseline at week 48
Secondary outcomes (3)
Achievement of liver fat <5%
Measured: At weeks 24 and 48
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Measured: Through week 72
Severity of TEAEs
Measured: Through week 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2026
- Study start22 May 2026
- Primary completion15 Mar 2030 (estimated)
- Study completion15 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)Studies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- 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
- 204 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07527910
- Sponsor's protocol ID
- ALN-PNP-MASLD-2543
- Status last verified
- Sep 2026
- First submitted
- 7 Apr 2026
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Part, Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study of ALN-PNP With and Without a GLP1R Agonist in Adults With Homozygous PNPLA3-Related Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
- ClinicalTrials.gov ID
- NCT07527910
- Acronym / sponsor ID
- ALN-PNP-MASLD-2543
- Keywords
- Homozygous PNPLA3-Related MASLD, Fatty Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis (MASH), Non-Alcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 204 participants (estimated)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 22 May 2026 (actual)
- Primary completion
- 15 Mar 2030 (estimated)
- Study completion
- 15 Mar 2030 (estimated)
- First posted
- 14 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test a study drug called ALN-PNP with and without another drug that is used for controlling blood sugar, appetite, and weight (for example, tirzepatide), to see if it can help treat MASLD, also known as fatty liver disease. ALN-PNP reduces the amount of Patatin-like phospholipase domain-containing protein 3 (PNPLA3), a protein that liver cells make, which may help decrease liver fat if there is an abnormal PNPLA3 protein.
The goal of this study is to understand the effect of ALN-PNP with or without tirzepatide on reducing liver fat.
The study is looking at:
- How well ALN-PNP with and without tirzepatide works
- What side effects ALN-PNP might cause
- How much ALN-PNP is in the blood at different times
- How the body and the liver change after having ALN-PNP, which can help researchers understand why ALN-PNP works better in some people than others
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part A: A1 | Experimental | Drug: ALN-PNP, Drug: Tirzepatide |
| Part A: A2 | Experimental | Drug: Tirzepatide, Drug: Placebo |
| Part B: B1 | Experimental | Drug: ALN-PNP, Drug: Tirzepatide |
| Part B: B2 | Experimental | Drug: Tirzepatide, Drug: Placebo |
| Part B: B3 | Experimental | Drug: ALN-PNP |
| Part B: B4 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Homozygous for the PNPLA3 p.I148M genotype
- Liver fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥15% at visit 3
- Has a Body Mass Index (BMI) ≥30 to <45 kg/m^2 at visit 2
- Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3 × Upper Limit of Normal (ULN) as described in the protocol
- On a stable dose of tirzepatide at randomization (≥5 mg weekly)
Key exclusion criteria (5 listed)
- Evidence or diagnosis of portal hypertension or cirrhosis from any cause, including cirrhosis due to MASH, as determined by the investigator, based on medical history, clinical assessment, imaging, and/or liver biopsy
- Known chronic liver disease other than MASLD, as determined by the investigator, as defined in the protocol
- Contraindications to MRI examinations, including but not limited to persons with MRI-incompatible cardiac pacemaker and implants made of metal, severe claustrophobia, size restrictions
- Any contraindication listed in the Zepbound United States Prescribing Information (USPI), as defined in the protocol
- NOTE: Other protocol-defined inclusion/exclusion criteria 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 |
|---|---|---|
| ALN-PNPAdministered per the protocol | Drug | Part A: A1, Part B: B1, Part B: B3 |
| TirzepatideAlso: Zepbound®Administered per the protocol | Drug | Part A: A1, Part A: A2, Part B: B1, Part B: B2 |
| PlaceboAdministered per the protocol Placebo matching ALN-PNP | Drug | Part A: A2, Part B: B2, Part B: B4 |
Primary outcome
Percent change in liver fat
Time frame: From baseline at week 24
Part A
Percent change in liver fat
Time frame: From baseline at week 48
Part B
3 secondary outcomes
Achievement of liver fat <5%
Time frame: At weeks 24 and 48
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: Through week 72
Severity of TEAEs
Time frame: Through week 72
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Related trials for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Not yet recruitingObservational study
Periodontal Status and Biomarkers in MASLD
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
Enrolling by invitation
Effect of Ancestry Supplementation in Subjects With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
MASLD
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
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.
Clinical Trial Management study director
Regeneron Pharmaceuticals
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ALN-PNP and Tirzepatide in people with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), run by Regeneron Pharmaceuticals at 9 sites in United States.
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 7 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: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in liver fat (time frame: From baseline at 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?
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 29 Sep 2026.