A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Non-Alcoholic Fatty Liver Disease (NAFLD)

Last updated: March 13, 2025
Sponsor: Regeneron Pharmaceuticals
Overall Status: Active - Not Recruiting

Phase

1

Condition

Primary Biliary Cholangitis

Liver Disease

Healthy Volunteers

Treatment

ALN-PNP - Part A

ALN-PNP - Part B

Placebo (PB)

Clinical Study ID

NCT05648214
ALN-PNP-HV-2227
  • Ages 18-65
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

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.

Part A is focused on healthy participants. Part B of the study is focused on participants who are known to have NAFLD 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.

Part A is looking at several other research questions, including:

  • What side effects may happen from taking the study drug

  • How much study drug is 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)

  • 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 B is looking at several other research questions, including:

  • What side effects may happen from taking the study drug

  • How the study drug works to change liver fat content in NAFLD

  • How much study drug and study drug metabolites (byproduct of the body breaking down the study drug) are in your blood at different times

  • Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

  • Better understanding of the study drug and NAFLD

Eligibility Criteria

Inclusion

Key Inclusion Criteria:

Part A (Healthy Adults):

  1. From 18 to 55 years of age

  2. For Japanese cohorts ONLY; the Japanese participant must:

  3. Be Japanese, born in Japan, and have both biologic parents and 4 biologicgrandparents who are ethnically Japanese and born in Japan

  4. Have maintained a Japanese lifestyle, with no significant change since leavingJapan, including having access to Japanese food and adhering to a Japanese diet

  5. Be living <10 years outside of Japan

  6. Has a body mass index between 18 and 32 kg/m^2, inclusive, at the screening visit

  7. Is judged by the investigator to be in good health, as described in the protocol

  8. Is in good health based on laboratory safety testing obtained at the screening visitand approximately within 24 hours prior to administration of study drug

Part B (Participants with NAFLD):

  1. From 18 to 65 years of age

  2. Body mass index (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) andBMI from 27.0 kg/m2 to 40.0 kg/m2, inclusive, for any other ethnicity at screeningvisit 1

  3. Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3

Exclusion

Key Exclusion Criteria:

Part A:

  1. History of clinically significant cardiovascular, respiratory, hepatic, renal,gastrointestinal, endocrine, hematological, psychiatric, neurological, ordermatologic disease, as assessed by the investigator, that may confound the resultsof the study or poses an additional risk to the participant by study participation

  2. Presents any concern to the study investigator that might confound the results ofthe study or poses an additional risk to the participant by their participation inthe study

  3. Hospitalized for any reason within 30 days of the screening visit

  4. Using the Modification of Diet in Renal Disease equation, has a glomerularfiltration rate as described in the protocol at the screening visit

  5. Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or totalbilirubin above the upper limit of normal (ULN) range

  6. Is a current smoker or former smoker, including e-cigarettes, who stopped smokingwithin 3 months prior to the screening visit

  7. Has a history of alcohol or drug abuse per investigator opinion

  8. Is positive for hepatitis C antibody and if so, positive for qualitative (ie,detected or not detected) hepatitis C virus ribonucleic acid (RNA) test at thescreening visit

Part B:

  1. Evidence of other forms of known chronic liver disease, as defined in the protocol

  2. Has a contraindication to MRI examinations, as defined in the protocol

  3. History of Type 1 diabetes

  4. Bariatric surgery within approximately 5 years prior or planned during the studyperiod

  5. Has lost or gained more than 4.0% body weight over the 3 months prior to or duringthe screening period

  6. Has known human immunodeficiency virus (HIV) infection, evidence of current orchronic hepatitis B virus (HBV) infection, or current or chronic hepatitis C virus (HCV) infection, as defined in the protocol

NOTE: Other protocol defined inclusion / exclusion criteria apply

Study Design

Total Participants: 23
Treatment Group(s): 3
Primary Treatment: ALN-PNP - Part A
Phase: 1
Study Start date:
December 27, 2022
Estimated Completion Date:
October 18, 2025

Connect with a study center

  • California Clinical Trials Medical Group

    Glendale, California 91206
    United States

    Site Not Available

  • Velocity Clinical research

    Los Angeles, California 90057
    United States

    Site Not Available

  • Genoma Research Group ,Inc

    Miami, Florida 33173
    United States

    Site Not Available

  • Med Research of Florida,LLC

    Miami, Florida 33186
    United States

    Site Not Available

  • Tandem Clinical Research

    Marrero, Louisiana 70072
    United States

    Site Not Available

  • Pioneer Research Solutions

    Houston, Texas 77099
    United States

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.