Clinical trial NCT06784349: ALN-APOC3 in Adult Participants With Dyslipidemia
Official title: A Phase 1/2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALN-APOC3 in Adult Participants With Dyslipidemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Dyslipidemia
Keywords: Lipids
Triglycerides
Cholesterol
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2025-01-20
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A: Sequential Part B: Parallel
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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

Primary outcomes:
measure: Incidence of treatment emergent adverse events (TEAEs)
timeFrame: Through Week 44
measure: Severity of TEAEs
timeFrame: Through Week 44
measure: Percent changes in fasting concentrations of high-density lipoprotein cholesterol (HDL-C)
timeFrame: Baseline to week 24
Secondary outcomes:
measure: Concentration of combined ALN-APOC3 and metabolites in plasma
timeFrame: Through Week 44
measure: Urinary excretion of combined ALN-APOC3 and metabolites
timeFrame: Through 24 Hours, After Treatment
measure: Percent change in fasting concentrations of APOC3
timeFrame: Baseline to Week 12
measure: Absolute change in fasting concentrations of APOC3
timeFrame: Baseline to Week 12
measure: Percent change in fasting concentrations of APOC3
timeFrame: Baseline to Week 24
measure: Absolute change in fasting concentrations of APOC3
timeFrame: Baseline to Week 24
measure: Percent change in fasting concentrations of HDL-C
timeFrame: Baseline to Week 12
measure: Absolute change in fasting concentrations of HDL-C
timeFrame: Baseline to Week 12
measure: Absolute change in fasting concentrations of HDL-C
timeFrame: Baseline to Week 24
measure: Percent change in fasting concentrations of low-density lipoprotein cholesterol (LDL-C)
timeFrame: Baseline to Week 12
measure: Absolute change in fasting concentrations of LDL-C
timeFrame: Baseline to Week 12
measure: Percent change in fasting concentrations of LDL-C
timeFrame: Baseline to Week 24
measure: Absolute change in fasting concentrations of LDL-C
timeFrame: Baseline to Week 24
measure: Percent change in fasting concentrations of triglycerides (TG)
timeFrame: Baseline to Week 12
measure: Absolute change in fasting concentrations of TG
timeFrame: Baseline to Week 12
measure: Percent change in fasting concentrations of TG
timeFrame: Baseline to Week 24
measure: Absolute change in fasting concentrations of TG
timeFrame: Baseline to Week 24
measure: Percent change in fasting concentrations of non-HDL-C
timeFrame: Baseline to Week 12
measure: Absolute change in fasting concentrations of non-HDL-C
timeFrame: Baseline to Week 12
measure: Percent change in fasting concentrations of non-HDL-C
timeFrame: Baseline to Week 24
measure: Absolute change in fasting concentrations of non-HDL-C
timeFrame: Baseline to Week 24
measure: Percent change in fasting concentrations of apolipoprotein-B (APOB)
timeFrame: Baseline to Week 12
measure: Absolute change in fasting concentrations of APOB
timeFrame: Baseline to Week 12
measure: Percent change in fasting concentrations of APOB
timeFrame: Baseline to Week 24
measure: Absolute change in fasting concentrations of APOB
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Chisinau
country: Moldova, Republic of
facility: Arensia Exploratory Medicine at the Republican Clinical Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: