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Not yet recruitingPhase 2

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

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)

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

0

Recruiting sites

Enrollment

204

estimated

Study population

MASH / NAFLD / liver fibrosis, Obesity / overweight

Key I/E criterion

BMI 30-45

Primary endpoint

Liver fat content, change

Identifiers

Registered as

NCT IDNCT07527910
Org study IDALN-PNP-MASLD-2543

Timeline

Milestones

Study first posted2026-04-14actual
Last update posted2026-04-14actual
Study start2026-04-20estimated
Primary completion2029-11-27estimated
Study completion2029-11-27estimated

Assets

Investigational agents

Study populations

Who this study enrolls

MASH / NAFLD / liver fibrosisObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years
Maximum age75 Years
SexAll
Healthy volunteersNot accepted

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.

Endpoints (5)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

MASH / liver
3
Safety / tolerability / PK
2

MASH / liver

3 endpoints
Primary/protocol endpoint

Percent change in liver fat

Time frame:From baseline at week 24

Liver fat content, change

percent change from baseline, improvement

Primary/protocol endpoint

Percent change in liver fat

Time frame:From baseline at week 48

Liver fat content, change

percent change from baseline, improvement

Secondary/protocol endpoint

Achievement of liver fat <5%

Time frame:At weeks 24 and 48

threshold achievement, improvement

Safety / tolerability / PK

2 endpoints
Secondary/protocol endpoint

Occurence of Treatment-Emergent Adverse Events (TEAEs)

Time frame:Through week 60

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Severity of TEAEs

Time frame:Through week 60

Treatment-emergent AEs (any)

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.