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NCT Number: NCT05648214

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)

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)

Recruiting

Interested in participating?

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

California Clinical Trials Medical Group, Glendale, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

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

Key Exclusion Criteria:

Part A:

  • 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
  • Has Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) or total bilirubin above the Upper Limit of Normal (ULN) range
  • Is a current smoker or former smoker, including e-cigarettes, who stopped smoking within 3 months prior to 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
  • Has a contraindication to MRI examinations, as defined in the protocol
  • History of Type 1 diabetes
  • 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 HCV infection, as defined in the protocol
  • 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

Treatment and study plan

ALN-PNP

Drug

Administered per the protocol

Placebo (PB)

Drug

Administered per the protocol

Primary outcomes

  1. Incidence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Up to Day 337

  2. Severity of TEAEs

    Time frame: Up to Day 337

Secondary outcomes

  1. Concentration of ALN-PNP and potential major metabolite(s) in plasma

    Time frame: Up to Day 337

  2. Incidence of Anti-Drug Antibodies (ADAs) to ALN-PNP

    Time frame: Up to Day 337

  3. Magnitude of ADAs to ALN-PNP

    Time frame: Up to Day 337

  4. Change in Low-Density Lipoprotein (LDL)

    Time frame: Baseline up to Day 169

    Part A

  5. Change in High-Density Lipoprotein (HDL)

    Time frame: Baseline up to Day 169

    Part A

  6. Change in TriGlyceride (TG)

    Time frame: Baseline up to Day 337

  7. Change in Apolipoprotein B (ApoB)

    Time frame: Baseline up to Day 337

  8. Change in liver fat fraction by Magnetic Resonance Imaging derived Proton-Density Fat Fraction (MRI-PDFF)

    Time frame: Baseline up to Day 253

    Part B and Part C

  9. Change in Low-Density Lipoprotein Cholesterol (LDL-C)

    Time frame: Baseline up to Day 337

    Part B and Part C

  10. Change in High-Density Lipoprotein Cholesterol (HDL-C)

    Time frame: Baseline up to Day 337

    Part B and Part C

  11. Change in Lipoprotein (a) (Lp[a])

    Time frame: Baseline up to Day 337

    Part B and Part C

  12. Change in Apolipoprotein A1 (ApoA1)

    Time frame: Baseline up to Day 337

    Part B and Part C

  13. Change in small dense Low-Density Lipoprotein (sdLDL)

    Time frame: Baseline up to Day 337

    Part C

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Administrator

CONTACT

[email protected]

844-734-6643

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Dec 13, 2022
Registry last updated
Apr 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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