ALN-APOC3 in Adult Participants With Dyslipidemia

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALN-APOC3 in Adult Participants With Dyslipidemia

This study is researching an experimental drug called ALN-APOC3 (called "study drug"). The study is focused on participants who have dyslipidemia (abnormal amounts of fats in the blood, including triglycerides and cholesterol), but who are otherwise healthy.

The aim of the study is to see how safe and effective the study drug is.

The study 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
• How the study drug changes lipid levels in the blood

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: ALN-APOC3; Drug: Matching Placebo

Detailed Description

The study will be conducted in 2 parts, Part A and Part B. Participants in Part A will be excluded from participating in Part B.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Moldova
  • Chisinau, Moldova, 2025
    • Arensia Exploratory Medicine at the Republican Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Judged by the investigator to be in good health based on medical history, physical examination, vital signs, Electrocardiograms (ECG's) and laboratory safety testing, as defined in the protocol

2. Participants can enter the study under one of the following options, as defined in the protocol:

   1. Currently not taking statin and have not been on statin therapy for the 3 months prior to screening, or
   2. On a stable dose of statin, taken continuously for 3 months
3. Fasting triglycerides concentrations ≥100 and <500 mg/dL (1.13 to 5.65 mmol/L) during screening visit, as defined in the protocol
4. Fasting LDL-C ≥70 (1.81 mmol/L) if on stable statin therapy OR if not on statin treatment, as defined in the protocol

Key Exclusion Criteria:

1. History of clinically significant cardiovascular (other than dyslipidemia), respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease, or any other concern, 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. Was hospitalized (ie, >24 hours) for any reason within 30 days of the screening visit
3. Is positive for Human Immunodeficiency Virus (HIV) or Hepatitis B surface Antigen (HBsAg) at the screening visit, as defined in the protocol
4. Is positive for hepatitis C antibody and positive for qualitative Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) test at the screening visit
5. Any malignancy, except for non-melanoma skin cancer or cervical/anus in-situ, that have been resected with no evidence of metastatic disease for 3 years prior to the screening visit

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALN-APOC3 Ascending Cohorts; Part A: Ascending Cohorts Randomized as described in the protocol May include optional cohorts	Drug: ALN-APOC3; Administered as per the protocol; Drug: Matching Placebo; Administered as per the protocol
Placebo Comparator: Placebo; Part A and Part B: Randomized as described in the protocol	Drug: Matching Placebo; Administered as per the protocol
Experimental: ALN-APOC3 low-dose; Part B: Parallel Arm Randomized as described in the protocol	Drug: ALN-APOC3; Administered as per the protocol
Experimental: ALN-APOC3 medium-dose; Part B: Parallel Arm Randomized as described in the protocol	Drug: ALN-APOC3; Administered as per the protocol
Experimental: ALN-APOC3 high-dose; Part B: Parallel Arm Randomized as described in the protocol	Drug: ALN-APOC3; Administered as per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of TEAEs		Through Week 44
Incidence of Treatment Emergent Adverse Events (TEAEs)		Through Week 44
Percent changes in fasting concentrations of High-Density Lipoprotein Cholesterol (HDL-C)	Part B Only	Baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of combined ALN-APOC3 and metabolites in plasma		Through Week 44
Urinary excretion of combined ALN-APOC3 and metabolites	Part A Only	Through 24 Hours, After Treatment
Percent change in fasting concentrations of APOC3		Baseline to Week 12
Absolute change in fasting concentrations of APOC3		Baseline to Week 12
Percent change in fasting concentrations of APOC3	Part B Only	Baseline to Week 24
Absolute change in fasting concentrations of APOC3	Part B Only	Baseline to Week 24
Percent change in fasting concentrations of HDL-C		Baseline to Week 12
Absolute change in fasting concentrations of HDL-C		Baseline to Week 12
Absolute change in fasting concentrations of HDL-C	Part B Only	Baseline to Week 24
Absolute change in fasting concentrations of LDL-C		Baseline to Week 12
Percent change in fasting concentrations of LDL-C	Part B Only	Baseline to Week 24
Absolute change in fasting concentrations of LDL-C	Part B Only	Baseline to Week 24
Absolute change in fasting concentrations of TG		Baseline to Week 12
Percent change in fasting concentrations of TG	Part B Only	Baseline to Week 24
Absolute change in fasting concentrations of TG	Part B Only	Baseline to Week 24
Percent change in fasting concentrations of non-HDL-C		Baseline to Week 12
Absolute change in fasting concentrations of non-HDL-C		Baseline to Week 12
Percent change in fasting concentrations of non-HDL-C	Part B Only	Baseline to Week 24
Absolute change in fasting concentrations of non-HDL-C	Part B Only	Baseline to Week 24
Absolute change in fasting concentrations of APOB		Baseline to Week 12
Percent change in fasting concentrations of APOB	Part B Only	Baseline to Week 24
Absolute change in fasting concentrations of APOB	Part B Only	Baseline to Week 24
Percent change in fasting concentrations of Low-Density Lipoprotein Cholesterol (LDL-C)		Baseline to Week 12
Percent change in fasting concentrations of Triglycerides (TG)		Baseline to Week 12
Percent change in fasting concentrations of Apolipoprotein-B (APOB)		Baseline to Week 12

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2025
• Primary Completion (Actual): February 25, 2026
• Study Completion (Actual): February 25, 2026

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): January 20, 2025

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cholesterol; Lipids; Triglycerides
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Dyslipidemias
• Other Study ID Numbers: ALN-APOC3-hLP-2447

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes