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)
- Conditions
- Non-alcoholic Fatty Liver Disease (NAFLD)Healthy Volunteers
- Interventions
- Drug: ALN-PNP - Part ADrug: ALN-PNP - Part BDrug: Placebo (PB)
- Registration Number
- NCT05648214
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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.
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 23
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 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 (Participants with NAFLD):
- From 18 to 65 years of age
- 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
- Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3
Key
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 ribonucleic acid (RNA) test at the screening visit
Part B:
- 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
- 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
NOTE: Other protocol defined inclusion / exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: ALN-PNP Dose 1 or PB ALN-PNP - Part A 8 Participants, Randomized 6:2 Part A: ALN-PNP Dose 1 or PB Placebo (PB) 8 Participants, Randomized 6:2 Part A: ALN-PNP Dose 2 or PB ALN-PNP - Part A 8 Participants, Randomized 6:2 Part A: ALN-PNP Dose 2 or PB Placebo (PB) 8 Participants, Randomized 6:2 Part A: ALN-PNP Dose 3 or PB ALN-PNP - Part A 8 Participants, Randomized 6:2 Part A: ALN-PNP Dose 3 or PB Placebo (PB) 8 Participants, Randomized 6:2 Part A: ALN-PNP Dose 4 or PB ALN-PNP - Part A 8 Participants, Randomized 6:2 Part A: ALN-PNP Dose 4 or PB Placebo (PB) 8 Participants, Randomized 6:2 Part A: ALN-PNP Dose 5 or PB Placebo (PB) 8 Participants, Randomized 6:2 Part A: Optional ALN-PNP Dose 5 or PB ALN-PNP - Part A 8 Participants, Randomized 6:2 This is an optional cohort, if there is a need for additional dose characterization of ALN-PNP. Part A: Optional ALN-PNP Dose 5 or PB Placebo (PB) 8 Participants, Randomized 6:2 This is an optional cohort, if there is a need for additional dose characterization of ALN-PNP. Part A: JPN ALN-PNP Dose 5 or PB ALN-PNP - Part A 8 Japanese Participants only, Randomized 6:2 Part A: JPN ALN-PNP Dose 5 or PB Placebo (PB) 8 Japanese Participants only, Randomized 6:2 Part B: Placebo Placebo (PB) Up to 32 Participants Randomized 1:1:1:1 resulting in 8 participants per arm Part A: JPN ALN-PNP Dose 4 or PB ALN-PNP - Part A 8 Japanese Participants only, Randomized 6:2 Part B: ALN-PNP Dose 5 ALN-PNP - Part B Up to 32 Participants Randomized 1:1:1:1 resulting in 8 participants per arm Part A: ALN-PNP Dose 5 or PB ALN-PNP - Part A 8 Participants, Randomized 6:2 Part A: JPN ALN-PNP Dose 4 or PB Placebo (PB) 8 Japanese Participants only, Randomized 6:2 Part B: ALN-PNP Dose 3 ALN-PNP - Part B Up to 32 Participants Randomized 1:1:1:1 resulting in 8 participants per arm Part B: ALN-PNP Dose 4 ALN-PNP - Part B Up to 32 Participants Randomized 1:1:1:1 resulting in 8 participants per arm
- Primary Outcome Measures
Name Time Method Incidence of TEAEs by severity Up to Day 253 Incidence of treatment-emergent adverse events (TEAEs) Up to Day 253
- Secondary Outcome Measures
Name Time Method Concentration of ALN-PNP and potential major metabolite(s) in plasma over time Up to Day 253 Change in low-density lipoprotein (LDL) over time Baseline up to Day 169 Part A
Change in high-density lipoprotein (HDL) over time Baseline up to Day 169 Part A
Change in apolipoprotein A1 (ApoA1) over time Baseline up to Day 253 Part B
Change in low-density lipoprotein cholesterol (LDL-C) over time Baseline up to Day 253 Part B
Change in high-density lipoprotein cholesterol (HDL-C) over time Baseline up to Day 253 Part B
Change in triglyceride (TG) over time Baseline up to Day 253 Incidence of ALN-PNP antidrug-antibodies (ADA) over time Up to Day 253 Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDF) over time Baseline up to Day 253 Part B
Change in apolipoprotein B (ApoB) over time Baseline up to Day 253 Titer of ALN-PNP ADA over time Up to Day 253 Change in lipoprotein (a) (Lp[a]) over time Baseline up to Day 253 Part B
Related Research Topics
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Trial Locations
- Locations (6)
California Clinical Trials Medical Group
🇺🇸Glendale, California, 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, United States
Tandem Clinical Research
🇺🇸Marrero, Louisiana, United States
Pioneer Research Solutions
🇺🇸Houston, Texas, United States