A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor

NCT06024408 | Completed Phase 1 FDA Drug

• 1 other identifier: ALN-PNP-NASH-2255
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

Brief Summary

This study is researching an experimental drug called ALN-PNP. This study is focused on participants who are known to have nonalcoholic fatty liver disease (NAFLD), and a specific variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene. The aim of this study is to see how safe, tolerable, and effective the study drug is. This study 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

Conditions

Nonalcoholic Fatty Liver Disease (NAFLD); Nonalcoholic Steatohepatitis (NASH); Genetic Risk Factor

Keywords

Homozygous; Heterozygous

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent adverse events (TEAEs)

  Up to 253 days

• Severity of TEAEs

  Up to 253 days

Secondary Outcomes (10)

• Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDFF) in participants with NAFLD

  Baseline up to 253 days

• Change in low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD

  Baseline up to 253 days

• Change in high-density lipoprotein cholesterol (HDL-C) in participants with NAFLD

  Baseline up to 253 days

• Change in triglycerides (TG) in participants with NAFLD

  Baseline up to 253 days

• Change in lipoprotein a (Lp(a)) in participants with NAFLD

  Baseline up to 253 days

Study Arms (10)

Part A: Placebo

PLACEBO COMPARATOR

Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1

Drug: Placebo

Part A: Low Dose

EXPERIMENTAL

Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1

Drug: ALN-PNP

Part A: Mid Dose

EXPERIMENTAL

Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1

Drug: ALN-PNP

Part A: High Dose

EXPERIMENTAL

Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1

Drug: ALN-PNP

Part B: Placebo

PLACEBO COMPARATOR

Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1

Drug: Placebo

Part B : Low Dose

EXPERIMENTAL

Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1

Drug: ALN-PNP

Part B: Mid Dose

EXPERIMENTAL

Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1

Drug: ALN-PNP

Part B: High Dose

EXPERIMENTAL

Participants who are homozygous for the PNPLA3 rs738409:G risk allele will be randomized 1:1:1:1

Drug: ALN-PNP

Part C: Placebo (Optional)

PLACEBO COMPARATOR

Sponsor may elect to enroll participants who are heterozygous for the PNPLA3 rs738409:G risk allele and may be randomized 1:1

Drug: Placebo

Part C: High Dose (Optional)

EXPERIMENTAL

Sponsor may elect to enroll participants who are heterozygous for the PNPLA3 rs738409:G risk allele and may be randomized 1:1

Drug: ALN-PNP

Interventions

ALN-PNP DRUG

Part A: Administered as single subcutaneous (SC) injection on day 1 Part B and Part C: Administered SC every 12 weeks (Q12W x2)

Part A: High Dose; Part A: Low Dose; Part A: Mid Dose; Part B : Low Dose; Part B: High Dose; Part B: Mid Dose; Part C: High Dose (Optional)

Placebo DRUG

Part A: Administered as single SC injection on day 1 Part B and Part C: Administered SC every 12 weeks (Q12W x2)

Part A: Placebo; Part B: Placebo; Part C: Placebo (Optional)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants from 18 (or country's legal age of adulthood) to 65 years of age, inclusive, at screening visit 1
• Body mass index (BMI) from 23.0 kg/m\^2 to 40.0 kg/m\^2, inclusive, for East Asians (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and BMI from 27.0 kg/m\^2 to 40.0 kg/m\^2, inclusive, for any other ethnicity at screening visit 1
• Meets genotype criteria for the rs738409:G PNPLA3 risk allele: homozygotes (for Part A and Part B) or heterozygotes (optional Part C); p.I148M variant (PNPLA3 rs738409:G \[p.I148M\]) at screening visit 1
• Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3
• Generally stable diet (based on participant's recall) for at least 3 months prior to the screening visit

You may not qualify if:

• Evidence of other forms of known chronic liver disease, as defined in the protocol
• Has a contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made out of metal (for example, cochlear implant, nerve stimulators, magnetic vascular clips, and metallic heart valve), severe claustrophobia, or other contraindications for MRI
• Is taking a medication to treat a co-morbid condition that is not permitted during the study
• Has any laboratory parameter assessments at screening, as defined in the protocol
• History of Type 1 diabetes
• Bariatric surgery within approximately 5 years prior or planned during the study period
• 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 hepatitis C virus (HCV) infection, as defined in the protocol
• Was hospitalized (ie, \>24 hours) for any reason within 30 days of the screening visit

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (5)

Chungbuk National University Hospital

Cheongju-si, Chungcheong Buk-do, 28644, South Korea

Location

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

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

Study Record Dates

• First Submitted: August 16, 2023
• First Posted: September 6, 2023
• Study Start: May 21, 2024
• Primary Completion: July 7, 2025
• Study Completion: July 7, 2025
• Last Updated: July 31, 2025

Record last verified: 2025-07

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

KR (5)