ALN-APOC3 in Adult Participants With Dyslipidemia

Phase 1

Recruiting

• Conditions: Dyslipidemia
• Interventions: Drug: ALN-APOC3; Drug: Matching Placebo

• Registration Number: NCT06784349
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

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

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 Timeline

• Study First Submitted: 2024-12-03
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-14
• Study First Posted: 2025-01-20
• Study Start: 2025-01-27
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-22
• Primary Completion: 2027-07-05
• Study Completion: 2027-07-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 136

Inclusion Criteria

1. Judged by the investigator to be in 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ALN-APOC3 Ascending Cohorts	Matching Placebo	Part A: Ascending Cohorts Randomized as described in the protocol May include optional cohorts
Placebo	Matching Placebo	Part A and Part B: Randomized as described in the protocol
ALN-APOC3 medium-dose	ALN-APOC3	Part B: Parallel Arm Randomized as described in the protocol
ALN-APOC3 Ascending Cohorts	ALN-APOC3	Part A: Ascending Cohorts Randomized as described in the protocol May include optional cohorts
ALN-APOC3 low-dose	ALN-APOC3	Part B: Parallel Arm Randomized as described in the protocol
ALN-APOC3 high-dose	ALN-APOC3	Part B: Parallel Arm Randomized as described in the protocol

Primary Outcome Measures

Name	Time	Method
Incidence of treatment emergent adverse events (TEAEs)	Through Week 44
Severity of TEAEs	Through Week 44
Percent changes in fasting concentrations of high-density lipoprotein cholesterol (HDL-C)	Baseline to week 24	Part B Only

Secondary Outcome Measures

Name	Time	Method
Percent change in fasting concentrations of TG	Baseline to Week 24	Part B Only
Absolute change in fasting concentrations of TG	Baseline to Week 24	Part B Only
Concentration of combined ALN-APOC3 and metabolites in plasma	Through Week 44
Urinary excretion of combined ALN-APOC3 and metabolites	Through 24 Hours, After Treatment	Part A Only
Percent change in fasting concentrations of APOC3	Baseline to Week 24	Part B Only
Absolute change in fasting concentrations of APOC3	Baseline to Week 24	Part B Only
Percent change in fasting concentrations of HDL-C	Baseline to Week 12
Absolute change in fasting concentrations of HDL-C	Baseline to Week 24	Part B Only
Percent change in fasting concentrations of low-density lipoprotein cholesterol (LDL-C)	Baseline to Week 12
Absolute change in fasting concentrations of LDL-C	Baseline to Week 24	Part B Only
Percent change in fasting concentrations of LDL-C	Baseline to Week 24	Part B Only
Percent change in fasting concentrations of triglycerides (TG)	Baseline to Week 12
Percent change in fasting concentrations of non-HDL-C	Baseline to Week 24	Part B Only
Absolute change in fasting concentrations of non-HDL-C	Baseline to Week 24	Part B Only
Percent change in fasting concentrations of apolipoprotein-B (APOB)	Baseline to Week 12
Absolute change in fasting concentrations of APOB	Baseline to Week 24	Part B Only
Percent change in fasting concentrations of APOB	Baseline to Week 24	Part B Only

Trial Locations

Locations (1)

Arensia Exploratory Medicine at the Republican Clinical Hospital; 🇲🇩 Chisinau, Moldova, Republic of