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)

Healthy Volunteers Clinical Trial

Official title:

A Two-Part, Phase 1, Randomized, Double-blind, Placebo-Controlled, Single Dose Study of the Safety, Tolerability, and Pharmacokinetics of ALN-PNP, an siRNA Targeting PNPLA3, in Healthy Adults and Adult Participants With NAFLD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05648214
• Other study ID #: ALN-PNP-HV-2227
• Status: Recruiting
• Phase: Phase 1
• Start date: December 27, 2022
• Est. completion date: September 10, 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 (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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: September 10, 2025
• Est. primary completion date: September 10, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

Part A (Healthy Adults):

1. From 18 to 55 years of age

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

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

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

3. Be living <10 years outside of Japan

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

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

5. 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 (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) and BMI from 27.0 kg/m2 to 40.0 kg/m2, inclusive, for any other ethnicity at screening visit 1

3. Liver fat content =8.5% as measured by MRI-PDFF at screening visit 3 Key Exclusion Criteria:

Part A:

1. 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

2. 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

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

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

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

6. Is a current smoker or former smoker, including e-cigarettes, who stopped smoking within 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 the screening 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 study period

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

6. 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 NOTE: Other protocol defined inclusion / exclusion criteria apply

Related Conditions & MeSH terms

• Fatty Liver
• Healthy Volunteers
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Fatty Liver Disease (NAFLD)

Intervention

Drug:
• ALN-PNP - Part A
Administered by subcutaneous (SC) single ascending dose (SAD)
• ALN-PNP - Part B
Administered by SC parallel single dose
• Placebo (PB)
Administered by SC injection

Locations

Country	Name	City	State
United States	California Clinical Trials Medical Group	Glendale	California
United States	Pioneer Research Solutions	Houston	Texas
United States	Velocity Clinical research	Los Angeles	California
United States	Genoma Research Group ,Inc	Miami	Florida
United States	Med Research of Florida,LLC	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)		Up to Day 253
Primary	Incidence of TEAEs by severity		Up to Day 253
Secondary	Concentration of ALN-PNP and potential major metabolite(s) in plasma over time		Up to Day 253
Secondary	Incidence of ALN-PNP antidrug-antibodies (ADA) over time		Up to Day 253
Secondary	Titer of ALN-PNP ADA over time		Up to Day 253
Secondary	Change in low-density lipoprotein (LDL) over time	Part A	Baseline up to Day 169
Secondary	Change in high-density lipoprotein (HDL) over time	Part A	Baseline up to Day 169
Secondary	Change in triglyceride (TG) over time		Baseline up to Day 253
Secondary	Change in apolipoprotein B (ApoB) over time		Baseline up to Day 253
Secondary	Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDF) over time	Part B	Baseline up to Day 253
Secondary	Change in low-density lipoprotein cholesterol (LDL-C) over time	Part B	Baseline up to Day 253
Secondary	Change in high-density lipoprotein cholesterol (HDL-C) over time	Part B	Baseline up to Day 253
Secondary	Change in lipoprotein (a) (Lp[a]) over time	Part B	Baseline up to Day 253
Secondary	Change in apolipoprotein A1 (ApoA1) over time	Part B	Baseline up to Day 253