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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 204
- 试验地点
- 6
- 主要终点
- Percent change in liver fat
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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.
研究组 & 干预措施
Part B: B3
干预措施: ALN-PNP (Drug)
Part A: A1
干预措施: Tirzepatide (Drug)
Part B: B1
干预措施: Tirzepatide (Drug)
Part B: B4
干预措施: Placebo (Drug)
Part B: B2
干预措施: Placebo (Drug)
Part A: A2
干预措施: Placebo (Drug)
Part A: A2
干预措施: Tirzepatide (Drug)
Part B: B1
干预措施: ALN-PNP (Drug)
Part B: B2
干预措施: Tirzepatide (Drug)
Part A: A1
干预措施: ALN-PNP (Drug)
结局指标
主要结局
Percent change in liver fat
时间窗: From baseline at week 24
Part A
Percent change in liver fat
时间窗: From baseline at week 48
Part B
次要结局
- 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)