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

Nonalcoholic Steatohepatitis (NASH) Clinical Trial

Official title:

A Three-Part, Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALN-PNP siRNA in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a PNPLA3 Genetic Risk Factor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06024408
• Other study ID #: ALN-PNP-NASH-2255
• Status: Recruiting
• Phase: Phase 1
• Start date: May 21, 2024
• Est. completion date: September 14, 2025

Study information

• Verified date: June 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: September 14, 2025
• Est. primary completion date: September 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key 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

Key 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 Note: Other protocol defined Inclusion/Exclusion Criteria apply

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease (NAFLD)
• Nonalcoholic Steatohepatitis (NASH)

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)		Up to 253 days
Primary	Severity of TEAEs		Up to 253 days
Secondary	Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDFF) in participants with NAFLD		Baseline up to 253 days
Secondary	Change in low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD		Baseline up to 253 days
Secondary	Change in high-density lipoprotein cholesterol (HDL-C) in participants with NAFLD		Baseline up to 253 days
Secondary	Change in triglycerides (TG) in participants with NAFLD		Baseline up to 253 days
Secondary	Change in lipoprotein a (Lp(a)) in participants with NAFLD		Baseline up to 253 days
Secondary	Change in apolipoprotein A1 (ApoA1) in participants with NAFLD		Baseline up to 253 days
Secondary	Change in apolipoprotein B (ApoB) in participants with NAFLD		Baseline up to 253 days
Secondary	Concentration of ALN-PNP and potential major metabolite(s) in plasma over time		Up to 253 days
Secondary	Incidence of anti-drug antibodies (ADAs) to ALN-PNP		Up to 253 days
Secondary	Titer of anti-drug antibodies (ADAs) to ALN-PNP		Up to 253 days