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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 204
- Locations
- 6
- Primary Endpoint
- Percent change in liver fat
Study Overview
Brief 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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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)
Exclusion Criteria
- •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.
Arms & Interventions
Part B: B3
Intervention: ALN-PNP (Drug)
Part A: A1
Intervention: Tirzepatide (Drug)
Part B: B1
Intervention: Tirzepatide (Drug)
Part B: B4
Intervention: Placebo (Drug)
Part B: B2
Intervention: Placebo (Drug)
Part A: A2
Intervention: Placebo (Drug)
Part A: A2
Intervention: Tirzepatide (Drug)
Part B: B1
Intervention: ALN-PNP (Drug)
Part B: B2
Intervention: Tirzepatide (Drug)
Part A: A1
Intervention: ALN-PNP (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Achievement of liver fat <5%(At weeks 24 and 48)
- Occurence of Treatment-Emergent Adverse Events (TEAEs)(Through week 60)
- Severity of TEAEs(Through week 60)
- Severity of TEAEs(Through week 72)
- Occurrence of Treatment-Emergent Adverse Events (TEAEs)(Through week 72)