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)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
156
Administered per the protocol
Administered per the protocol
California Clinical Trials Medical Group
Glendale, California, United States
COMPLETEDVelocity Clinical research
Los Angeles, California, United States
RECRUITINGGenoma Research Group, Inc
Miami, Florida, United States
RECRUITINGMed Research of Florida, LLC
Miami, Florida, United States
RECRUITINGTandem Clinical Research
Marrero, Louisiana, United States
RECRUITINGPioneer Research Solutions
Houston, Texas, United States
RECRUITINGIncidence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to Day 253
Severity of TEAEs
Time frame: Up to Day 253
Concentration of ALN-PNP and potential major metabolite(s) in plasma
Time frame: Up to Day 253
Incidence of Anti-Drug Antibodies (ADAs) to ALN-PNP
Time frame: Up to Day 253
Magnitude of ADAs to ALN-PNP
Time frame: Up to Day 253
Change in Low-Density Lipoprotein (LDL)
Part A
Time frame: Baseline up to Day 169
Change in High-Density Lipoprotein (HDL)
Part A
Time frame: Baseline up to Day 169
Change in TriGlyceride (TG)
Time frame: Baseline up to Day 253
Change in Apolipoprotein B (ApoB)
Time frame: Baseline up to Day 253
Change in liver fat fraction by Magnetic Resonance Imaging derived Proton-Density Fat Fraction (MRI-PDFF)
Part B and Part C
Time frame: Baseline up to Day 253
Change in Low-Density Lipoprotein Cholesterol (LDL-C)
Part B and Part C
Time frame: Baseline up to Day 253
Change in High-Density Lipoprotein Cholesterol (HDL-C)
Part B and Part C
Time frame: Baseline up to Day 253
Change in Lipoprotein (a) (Lp[a])
Part B and Part C
Time frame: Baseline up to Day 253
Change in Apolipoprotein A1 (ApoA1)
Part B and Part C
Time frame: Baseline up to Day 253
Change in small dense Low-Density Lipoprotein (sdLDL)
Part C
Time frame: Baseline up to Day 253
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