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

NCT ID: NCT06024408

Last Updated: 2025-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-21
• Study Completion Date: 2025-07-07

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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: Low Dose

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

Group Type: EXPERIMENTAL

ALN-PNP

Intervention Type: 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: Mid Dose

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

Group Type: EXPERIMENTAL

ALN-PNP

Intervention Type: 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

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

Group Type: EXPERIMENTAL

ALN-PNP

Intervention Type: 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 B: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Part B : Low Dose

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

Group Type: EXPERIMENTAL

ALN-PNP

Intervention Type: 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 B: Mid Dose

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

Group Type: EXPERIMENTAL

ALN-PNP

Intervention Type: 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 B: High Dose

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

Group Type: EXPERIMENTAL

ALN-PNP

Intervention Type: 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 C: Placebo (Optional)

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Part C: High Dose (Optional)

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

Group Type: EXPERIMENTAL

ALN-PNP

Intervention Type: DRUG

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

Interventions

ALN-PNP

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Participants from 18 (or country's legal age of adulthood) to 65 years of age, inclusive, at screening visit 1

2. 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

3. 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

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

5. Generally stable diet (based on participant's recall) for at least 3 months prior to the screening visit

Exclusion Criteria

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

2. 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

3. Is taking a medication to treat a co-morbid condition that is not permitted during the study

4. Has any laboratory parameter assessments at screening, as defined in the protocol

5. History of Type 1 diabetes

6. Bariatric surgery within approximately 5 years prior or planned during the study period

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

8. 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

9. Was hospitalized (ie, >24 hours) for any reason within 30 days of the screening visit

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

Chungbuk National University Hospital

Cheongju-si, Chungcheong Buk-do, South Korea

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Countries

South Korea

Other Identifiers

ALN-PNP-NASH-2255

Identifier Type: -

Identifier Source: org_study_id