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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)

Phase 1
Recruiting
Conditions
Healthy Volunteers
Non-alcoholic Fatty Liver Disease (NAFLD)
Registration Number
NCT05648214
Lead Sponsor
Regeneron Pharmaceuticals
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
96
Inclusion Criteria

Key Inclusion Criteria:<br><br>Part A (Healthy Adults):<br><br> 1. From 18 to 55 years of age<br><br> 2. For Japanese cohorts ONLY; the Japanese participant must:<br><br> 1. Be Japanese, born in Japan, and have both biologic parents and 4 biologic<br> grandparents who are ethnically Japanese and born in Japan<br><br> 2. Have maintained a Japanese lifestyle, with no significant change since leaving<br> Japan, including having access to Japanese food and adhering to a Japanese diet<br><br> 3. Be living <10 years outside of Japan<br><br> 3. Has a body mass index between 18 and 32 kg/m^2, inclusive, at the screening visit<br><br> 4. Is judged by the investigator to be in good health, as described in the protocol<br><br> 5. Is in good health based on laboratory safety testing obtained at the screening visit<br> and approximately within 24 hours prior to administration of study drug<br><br>Part B (Participants with NAFLD):<br><br> 1. From 18 to 65 years of age<br><br> 2. Body mass index (BMI) from 23.0 kg/m2 to 40.0 kg/m2, inclusive, for East Asians<br> (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and<br> BMI from 27.0 kg/m2 to 40.0 kg/m2, inclusive, for any other ethnicity at screening<br> visit 1<br><br> 3. Liver fat content =8.5% as measured by MRI-PDFF at screening visit 3<br><br>Key Exclusion Criteria:<br><br>Part A:<br><br> 1. History of clinically significant cardiovascular, respiratory, hepatic, renal,<br> gastrointestinal, endocrine, hematological, psychiatric, neurological, or<br> dermatologic disease, as assessed by the investigator, that may confound the results<br> of the study or poses an additional risk to the participant by study participation<br><br> 2. Presents any concern to the study investigator that might confound the results of<br> the study or poses an additional risk to the participant by their participation in<br> the study<br><br> 3. Hospitalized for any reason within 30 days of the screening visit<br><br> 4. Using the Modification of Diet in Renal Disease equation, has a glomerular<br> filtration rate as described in the protocol at the screening visit<br><br> 5. Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total<br> bilirubin above the upper limit of normal (ULN) range<br><br> 6. Is a current smoker or former smoker, including e-cigarettes, who stopped smoking<br> within 3 months prior to the screening visit<br><br> 7. Has a history of alcohol or drug abuse per investigator opinion<br><br> 8. Is positive for hepatitis C antibody and if so, positive for qualitative (ie,<br> detected or not detected) hepatitis C virus ribonucleic acid (RNA) test at the<br> screening visit<br><br>Part B:<br><br> 1. Evidence of other forms of known chronic liver disease, as defined in the protocol<br><br> 2. Has a contraindication to MRI examinations, as defined in the protocol<br><br> 3. History of Type 1 diabetes<br><br> 4. Bariatric surgery within approximately 5 years prior or planned during the study<br> period<br><br> 5. Has lost or gained more than 4.0% body weight over the 3 months prior to or during<br> the screening period<br><br> 6. Has known human immunodeficiency virus (HIV) infection, evidence of current or<br> chronic hepatitis B virus (HBV) infection, or current or chronic hepatitis C virus<br> (HCV) infection, as defined in the protocol<br><br>NOTE: Other protocol defined inclusion / exclusion criteria apply

Exclusion Criteria

Not provided

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Incidence of treatment-emergent adverse events (TEAEs);Incidence of TEAEs by severity
Secondary Outcome Measures
NameTimeMethod
Concentration of ALN-PNP and potential major metabolite(s) in plasma over time;Incidence of ALN-PNP antidrug-antibodies (ADA) over time;Titer of ALN-PNP ADA over time;Change in low-density lipoprotein (LDL) over time;Change in high-density lipoprotein (HDL) over time;Change in triglyceride (TG) over time;Change in apolipoprotein B (ApoB) over time;Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDF) over time;Change in low-density lipoprotein cholesterol (LDL-C) over time;Change in high-density lipoprotein cholesterol (HDL-C) over time;Change in lipoprotein (a) (Lp[a]) over time;Change in apolipoprotein A1 (ApoA1) over time
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