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)

NCT05648214 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ALN-PNP-HV-2227
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 6

Brief 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. 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)

Conditions

Healthy Volunteers; Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Keywords

Liver steatosis; Fibrosis; Hepatocytes; Non-Alcoholic Steatohepatitis (NASH); Non-Alcoholic Fatty Liver Disease (NAFLD); Metabolic dysfunction-Associated Steatohepatitis (MASH)

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  Up to Day 337

• Severity of TEAEs

  Up to Day 337

Secondary Outcomes (13)

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

  Up to Day 337

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

  Up to Day 337

• Magnitude of ADAs to ALN-PNP

  Up to Day 337

• Change in Low-Density Lipoprotein (LDL)

  Baseline up to Day 169

• Change in High-Density Lipoprotein (HDL)

  Baseline up to Day 169

Study Arms (5)

Part A: Cohorts

EXPERIMENTAL

Drug: ALN-PNP; Drug: Placebo (PB)

Part A: Optional Cohort

EXPERIMENTAL

Drug: ALN-PNP; Drug: Placebo (PB)

Part A: JPN Cohorts

EXPERIMENTAL

Drug: ALN-PNP; Drug: Placebo (PB)

Part B: Cohorts

EXPERIMENTAL

Drug: ALN-PNP; Drug: Placebo (PB)

Part C: Cohorts

EXPERIMENTAL

Drug: ALN-PNP; Drug: Placebo (PB)

Interventions

ALN-PNP DRUG

Administered per the protocol

Part A: Cohorts; Part A: JPN Cohorts; Part A: Optional Cohort; Part B: Cohorts; Part C: Cohorts

Placebo (PB) DRUG

Administered per the protocol

Part A: Cohorts; Part A: JPN Cohorts; Part A: Optional Cohort; Part B: Cohorts; Part C: Cohorts

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (6)

California Clinical Trials Medical Group

Glendale, California, 91206, United States

COMPLETED

Velocity Clinical research

Los Angeles, California, 90057, United States

RECRUITING

Genoma Research Group, Inc

Miami, Florida, 33173, United States

RECRUITING

Med Research of Florida, LLC

Miami, Florida, 33186, United States

RECRUITING

Tandem Clinical Research

Marrero, Louisiana, 70072, United States

RECRUITING

Pioneer Research Solutions

Houston, Texas, 77099, United States

RECRUITING

MeSH Terms

Conditions

Fatty Liver; Fibrosis; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials Administrator

CONTACT

844-734-6643; clinicaltrials@regeneron.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1: Part A (Sequential Ascending Dose) and Part B (Parallel Assignment) Phase 2a: Part C (Parallel Assignment)

Study Record Dates

• First Submitted: December 5, 2022
• First Posted: December 13, 2022
• Study Start: December 27, 2022
• Primary Completion (Estimated): August 10, 2027
• Study Completion (Estimated): August 10, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has: * received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development * made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry) * the legal authority to share the data, and * ensured the ability to protect participant privacy
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

US (6)