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

Официальное название

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)

Обзор

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

Вмешательства

• Препарат ALN-PNP
  Administered per the protocol
• Препарат Tirzepatide
  Administered per the protocol
• Препарат Placebo
  Administered per the protocol Placebo matching ALN-PNP

Первичные конечные точки

• Percent change in liver fat [Срок оценки: From baseline at week 24]
• Percent change in liver fat [Срок оценки: From baseline at week 48]

Вторичные конечные точки (3)

• Achievement of liver fat <5% [Срок оценки: At weeks 24 and 48]
• Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Through week 72]
• Severity of TEAEs [Срок оценки: Through week 72]

Критерии участия

Критерии включения

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)

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Southern California Research Center — Coronado
• California Liver Research Institute — Pasadena
• Tandem Clinical Research, Plaza II — Metairie
• Advanced Medical Trials — Georgetown
• American Research Corporation at The Texas Liver Institute — San Antonio

Идентификаторы

NCT: NCT07527910 · ALN-PNP-MASLD-2543

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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