This study is researching an experimental drug called ALN-PNP (called "study drug"). This is a first in human study. The study drug is not approved by any public health agency such as the United States Food and Drug Administration (FDA) for any kind of treatment.
This study consists of 3 parts. Part A is focused on healthy participants. Parts B and C of the study are focused on participants who are known to have MASLD and a specific variant of the PNPLA3 gene.
The aim of the study is to see how safe, tolerable and effective the study drug is.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drug (Parts A, B and C) * How much study drug (Parts A, B and C) and study drug metabolites (byproduct of the body breaking down the study drug) (Parts B and C) are in the blood at different times * Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects) (Part A, B and C) * Explore impact of Japanese ethnicity on safety and PK (Pharmacokinetics, or study of what the body does to the drug) of single doses of ALN-PNP over time (Part A) * How the study drug works to change liver fat content in MASLD (Part B and C) * Better understanding of the study drug and MASLD (Part B and C)
From 18 to 55 years of age
Be Japanese, born in Japan, and have both biologic parents and 4 biologic grandparents who are ethnically Japanese and born in Japan
Have maintained a Japanese lifestyle, with no significant change since leaving Japan, including having access to Japanese food and adhering to a Japanese diet
Be living <10 years outside of Japan
History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, neurological, or dermatologic disease, as assessed by the investigator, that may confound the results of the study or poses an additional risk to the participant by study participation
Presents any concern to the study investigator that might confound the results of the study or poses an additional risk to the participant by their participation in the study
Hospitalized for any reason within 30 days of the screening visit
Using the Modification of Diet in Renal Disease equation, has a glomerular filtration rate as described in the protocol at the screening visit