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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)
Lead sponsor
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
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
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 endpointsPercent change in liver fat
Time frame:From baseline at week 24
Liver fat content, change
percent change from baseline, improvement
Percent change in liver fat
Time frame:From baseline at week 48
Liver fat content, change
percent change from baseline, improvement
Achievement of liver fat <5%
Time frame:At weeks 24 and 48
threshold achievement, improvement
Safety / tolerability / PK
2 endpointsOccurence of Treatment-Emergent Adverse Events (TEAEs)
Time frame:Through week 60
Treatment-emergent AEs (any)
event count, event
Severity of TEAEs
Time frame:Through week 60
Treatment-emergent AEs (any)
descriptive
Provenance
Sources
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.