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NCT05648214RecruitingPhase 1/2

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

A Three-Part, Phase 1/2a, Randomized, Double-blind, Placebo-Controlled, Single and Multiple Dose Study of the Safety, Tolerability, and Pharmacokinetics of ALN-PNP, an siRNA Targeting PNPLA3, in Healthy Adults and Adult Participants With MASLD

Source: ClinicalTrials.gov · Last updated 16 Apr 2026

Brief summary (registry, in English)

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)

Status (registry)
Recruiting
Phase (registry)
Phase 1/2
Study type
Interventional
Enrollment
172 (estimated)
First submitted
5 Dec 2022
Start date
27 Dec 2022
Primary completion date
10 Aug 2027
Lead sponsor
Regeneron Pharmaceuticals
NCT number
NCT05648214

What you commit to

  • Study type: Interventional · Phase 1/2
  • Planned participants: 172
  • From 27 Dec 2022 to the primary completion date, 10 Aug 2027
  • 6 sites in 1 country
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

  • Is a current smoker or former smoker, including e-cigarettes, who stopped smoking within 3 months prior to the screening visit
  • Has lost or gained more than 4.0% body weight over the 3 months prior to or during the screening period
  • Bariatric surgery within approximately 5 years (Part B) or 3 years (Part C) prior or planned during the study period
    • NOTE: Other protocol defined inclusion / exclusion criteria apply

Other illness

  • 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
  • Using the Modification of Diet in Renal Disease equation, has a glomerular filtration rate as described in the protocol at the screening visit
  • Has a history of alcohol or drug abuse per investigator opinion
  • Is positive for hepatitis C antibody and if so, positive for qualitative (ie, detected or not detected) Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) test at the screening visit
    • Part B and Part C:
  • Evidence of other forms of known chronic liver disease, as defined in the protocol
  • History of Type 1 diabetes
  • Has known Human Immunodeficiency Virus (HIV) infection, evidence of current or chronic Hepatitis B Virus (HBV) infection, or current or chronic HCV infection, as defined in the protocol

Lab values

  • Has Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) or total bilirubin above the Upper Limit of Normal (ULN) range

Other

  • Part A:
  • 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
  • Has a contraindication to MRI examinations, as defined in the protocol

Who the study is looking for

  • Part A (Healthy Adults):
  • From 18 to 55 years of age
  • For Japanese cohorts ONLY; the Japanese participant must:
    • 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
  • Has a Body Mass Index (BMI) between 18 and 32 kg/m\^2, inclusive, at the screening visit
  • Is judged by the investigator to be in good health, as described in the protocol
  • Is in good health based on laboratory safety testing obtained at the screening visit and approximately within 24 hours prior to administration of study drug
    • Part B and Part C (Participants with MASLD):
  • Part B: From 18 to 65 years of age
  • Part C: From 18 to 75 years of age
  • BMI from 23.0 kg/m2 to 40.0 kg/m2, inclusive, for East Asians (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and BMI from 27.0 kg/m2 to 40.0 kg/m2, inclusive, for any other ethnicity at screening visit 1
  • Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3

Age in the registry: 18 years to 75 years · Sex: All · Accepts healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (6)

Sites in registry order. Pick your city on the disease page to sort them by distance.

SiteCityCountrySite status
California Clinical Trials Medical Group
Coordinator of this site? Confirm its status
GlendaleUnited StatesCompleted
Pioneer Research Solutions
Coordinator of this site? Confirm its status
HoustonUnited StatesRecruiting
Velocity Clinical Research
Coordinator of this site? Confirm its status
Los AngelesUnited StatesRecruiting
Tandem Clinical Research
Coordinator of this site? Confirm its status
MarreroUnited StatesRecruiting
Med Research of Florida, LLC
Coordinator of this site? Confirm its status
MiamiUnited StatesRecruiting
Genoma Research Group, Inc.
Coordinator of this site? Confirm its status
MiamiUnited StatesRecruiting

This page is information, not medical advice. Discuss any trial with your doctor.