Phase 3 Study of Plozasiran in Adults With Hypertriglyceridemia

Phase 3

Active, not recruiting

• Conditions: Hypertriglyceridemia
• Interventions: Drug: Placebo; Drug: Plozasiran Injection

• Registration Number: NCT06347133
• Lead Sponsor: Arrowhead Pharmaceuticals

Brief Summary

This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with hypertriglyceridemia (HTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo and be evaluated for efficacy and safety.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-29
• Study First Submitted QC: 2024-03-29
• Study First Posted: 2024-04-04
• Study Start: 2024-05-21
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-07
• Last Update Posted: 2025-07-10
• Primary Completion: 2026-07
• Study Completion: 2026-10-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1456

Inclusion Criteria

• Established diagnosis of hypertriglyceridemia (HTG) and prior documented evidence (medical history) of mean fasting TG level ≥150 mg/dL (≥1.69 mm/L) and ≤499 mg/dL (≤5.64 mmol/L)
• Mean fasting TG level ≥150 mg/dL (≥1.69 mmol/L) and ≤499 mg/dL (≤5.64 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
• Fasting low density lipoprotein-cholesterol (LDL-C) ≤ 130 mg/dL (≤3.37 mmol/L) at screening
• Screening HbA1c ≤9%
• Willing to follow diet counseling and maintain a stable low-fat diet
• Must be on standard of care lipid and TG-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator, including an inability to safely administer or re-administer a specific drug because of fear, preference, genetic, clinical, or metabolic considerations, or due a previous adverse reaction associated with, attributed to, or caused by specific drug) prior to collection of qualifying TG levels.

Exclusion Criteria

• Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1 (except inclisiran, which is permitted). Administration of investigational drug and inclisiran must be separated by at least 4 weeks.
• Use of any other hepatocyte targeted siRNA or antisense Oligonucleotide molecule within 60 days or within 5-half-lives before Day 1 based on plasma pharmacokinetics (PK), whichever is longer
• Acute pancreatitis within 4 weeks prior to screening
• Body mass index >45 kg/m^2

Note: Additional Inclusion/Exclusion criteria may apply per protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	calculated volume to match active treatment by sc injection
Plozasiran Injection	Plozasiran Injection	4 doses of plozasiran by subcutaneous (sc) injection

Primary Outcome Measures

Name	Time	Method
Percent Change in Fasting Serum Triglyceride (TG) Levels from Baseline to Month 12 Compared to Placebo	Baseline, Month 12

Secondary Outcome Measures

Name	Time	Method
Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo	Baseline, Month 10
Proportion of Participants who Achieve Fasting TG Levels of <150 mg/dL (<1.69 mmol/L) at Month 12 Compared to Placebo	Month 10, Month 12
Percent change in remnant cholesterol (VLDL-C) from baseline to Month 12	Baseline, Month 12
Percent change in non-HDL-C from baseline to Month 12 compared to placebo	Baseline, Month 12
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Over Time through Month 12 as Compared to Placebo	From first dose of study drug through Month 12
Incidence Rates of New-Onset Diabetes Mellitus (NODM) Throughout the Course of Treatment	From first dose of study drug through Month 12
Incidence Rates of Worsening of Existing Diabetes Throughout the Course of Treatment	From first dose of study drug through Month 12
Change from Baseline in Hemoglobin A1c (HbA1c) During the Treatment Period Compared to Placebo	From first dose of study drug through Month 12
Change from Baseline in Fasting Blood Glucose During the Treatment Period Compared to Placebo	From first dose of study drug through Month 12
Change from Baseline in C-peptide During the Treatment Period Compared to Placebo	From first dose of study drug through Month 12
Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) During the Treatment Period Compared to Placebo	From first dose of study drug through Month 12
Change from Baseline in Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) Associated with Worsening Glycemic Control During the Treatment Period Compared to Placebo	From first dose of study drug through Month 12
Initiation of New Medication for Hyperglycemia Among Study Participants Not Known to Have Pre-existing Diabetes Mellitus During the Treatment Period Compared to Placebo	From first dose of study drug through Month 12
Adjudicated Major Adverse Cardiovascular Events (MACE) Rates During the Treatment Period Compared to Placebo	From first dose of study drug through Month 12
Incidence of Anti-drug Antibodies (ADA) to Plozasiran in Participants Receiving Plozasiran Over Time Through Month 12	From first dose of study drug through Month 12
Titers of Anti-drug Antibodies (ADA) to Plozasiran in Participants Receiving Plozasiran Over Time Through Month 12	From first dose of study drug through Month 12

Trial Locations

Locations (231)

Ascension St. Vincents Birmingham; 🇺🇸 Birmingham, Alabama, United States

IMC Diagnostic and Medical Clinic, LLC; 🇺🇸 Mobile, Alabama, United States

National Heart Institute; 🇺🇸 Beverly Hills, California, United States

Hope Clinical Research; 🇺🇸 Canoga Park, California, United States

National Institute of Clinical Research; 🇺🇸 Garden Grove, California, United States

National Institute of Clinical Research, Inc.; 🇺🇸 Huntington Beach, California, United States

Orange County Research Center, Inc.; 🇺🇸 Lake Forest, California, United States

Clinical Trials Research; 🇺🇸 Lincoln, California, United States

VA Long Beach Healthcare System; 🇺🇸 Long Beach, California, United States

Catalina Research Institute, LLC; 🇺🇸 Montclair, California, United States

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