A Trial to Learn if Having ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor
Nonalcoholic Steatohepatitis, Genetic Risk Factor
About this trial
This is an interventional treatment trial for Nonalcoholic Steatohepatitis focused on measuring NASH, Nonalcoholic Fatty Liver Disease, NAFLD
Eligibility Criteria
Key Inclusion Criteria: Participants from 18 (or country's legal age of adulthood) to 65 years of age, inclusive, at screening visit 1 Body mass index (BMI) from 23.0 kg/m^2 to 40.0 kg/m^2, inclusive, for East Asians (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and BMI from 27.0 kg/m^2 to 40.0 kg/m^2, inclusive, for any other ethnicity at screening visit 1 Meets genotype criteria for the rs738409:G PNPLA3 risk allele: homozygotes or heterozygotes; p.I148M variant (PNPLA3 rs738409:G [p.I148M]) at screening visit 1 Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3 Generally stable diet (based on participant's recall) for at least 3 months prior to the screening visit Key Exclusion Criteria: Evidence of other forms of known chronic liver disease, as defined in the protocol Has a contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made out of metal (for example, cochlear implant, nerve stimulators, magnetic vascular clips, and metallic heart valve), severe claustrophobia, or other contraindications for MRI Is taking a medication to treat a co-morbid condition that is not permitted during the study Has any laboratory parameter assessments a screening, as defined in the protocol History of Type 1 diabetes Bariatric surgery within approximately 5 years prior or planned during the study period Has lost or gained more than 4.0% body weight over the 3 months prior to or during the screening period Has known human immunodeficiency virus (HIV) infection, evidence of current or chronic hepatitis B virus (HBV) infection, or current or chronic hepatitis C virus (HCV) infection, as defined in the protocol Was hospitalized (ie, >24 hours) for any reason within 30 days of the screening visit Note: Other protocol defined Inclusion/Exclusion Criteria apply
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort 1
Cohort 2
Participants who are homozygous for the PNPLA3 risk allele (G/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo
Participants who are heterozygous for the PNPLA3 risk allele (C/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo