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RecruitingNCT07527910Updated Sep 29, 2026

A Phase 2a Study of ALN-PNP With and Without a GLP1R Agonist in Adult Patients With Homozygous PNPLA3-Related MASLD

A Phase 2 interventional study of ALN-PNP and Tirzepatide in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), sponsored by Regeneron Pharmaceuticals. Recruiting at 9 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Regeneron Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
204
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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. 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
02

Conditions studied

  • Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Keywords

  • Homozygous PNPLA3-Related MASLD
  • Fatty Liver Disease
  • Metabolic Dysfunction-Associated Steatohepatitis (MASH)
  • Non-Alcoholic Fatty Liver Disease (NAFLD)
  • Nonalcoholic Steatohepatitis (NASH)
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

Part A and Part B:

  1. Homozygous for the PNPLA3 p.I148M genotype
  2. Liver fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥15% at visit 3
  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:

  1. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3 × Upper Limit of Normal (ULN) as described in the protocol
  2. On a stable dose of tirzepatide at randomization (≥5 mg weekly)

Key Exclusion Criteria:

  1. 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
  2. Known chronic liver disease other than MASLD, as determined by the investigator, as defined in the protocol
  3. Contraindications to MRI examinations, including but not limited to persons with MRI-incompatible cardiac pacemaker and implants made of metal, severe claustrophobia, size restrictions
  4. Any contraindication listed in the Zepbound United States Prescribing Information (USPI), as defined in the protocol

NOTE: Other protocol-defined inclusion/exclusion criteria apply.

04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
204 participants (estimated)

Study arms

  • Experimental
    Part A: A1

    Drug: ALN-PNP · Drug: Tirzepatide

  • Experimental
    Part A: A2

    Drug: Tirzepatide · Drug: Placebo

  • Experimental
    Part B: B1

    Drug: ALN-PNP · Drug: Tirzepatide

  • Experimental
    Part B: B2

    Drug: Tirzepatide · Drug: Placebo

  • Experimental
    Part B: B3

    Drug: ALN-PNP

  • Placebo comparator
    Part B: B4

    Drug: Placebo

Interventions

  • DrugALN-PNP

    Administered per the protocol

  • DrugTirzepatide

    Administered per the protocol

    Also known as: Zepbound®

  • DrugPlacebo

    Administered per the protocol Placebo matching ALN-PNP

05

What researchers measure

Primary outcomes

  1. Percent change in liver fat

    Part A

    Time frame: From baseline at week 24

  2. Percent change in liver fat

    Part B

    Time frame: From baseline at week 48

Secondary outcomes

  1. Achievement of liver fat <5%

    Time frame: At weeks 24 and 48

  2. Occurrence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Through week 72

  3. Severity of TEAEs

    Time frame: Through week 72

06

Study locations

9 of 9 sites recruiting
  • Arizona Liver Health - Tucson
    Tucson, Arizona 85712, United States
    Recruiting
  • Southern California Research Center
    Coronado, California 92118, United States
    Recruiting
  • California Liver Research Institute
    Pasadena, California 91105, United States
    Recruiting
  • Health Awareness, Inc
    Jupiter, Florida 33458, United States
    Recruiting
  • Evolution Clinical Trials
    Miami, Florida 33122, United States
    Recruiting
  • Tandem Clinical Research, Plaza II
    Metairie, Louisiana 70006, United States
    Recruiting
  • American Research Corporation
    Austin, Texas 78757, United States
    Recruiting
  • Advanced Medical Trials
    Georgetown, Texas 78628, United States
    Recruiting
  • American Research Corporation at The Texas Liver Institute
    San Antonio, Texas 78215, United States
    Recruiting
07

References and documents

Individual participant data

Plan to share: Yes — All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

Supporting information: Study protocol, Sap, Icf, Csr, Analytic code

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07527910
Lead sponsor
Regeneron Pharmaceuticals
Responsible party
Sponsor
First posted
Apr 14, 2026
Start date
May 22, 2026
Primary completion
Mar 15, 2030 (estimated)
Completion
Mar 15, 2030 (estimated)
Last update
Sep 29, 2026

Study contacts

Clinical Trials Administrator
Contact
clinicaltrials@regeneron.com
844-734-6643
Clinical Trial Management
study director · Regeneron Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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