Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia

Phase 3

Not yet recruiting

• Conditions: Hypertriglyceridemia
• Interventions: Drug: Plozasiran Injection

• Registration Number: NCT06822790
• Lead Sponsor: Arrowhead Pharmaceuticals

Brief Summary

This is an open-label study to be conducted in adults with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (SHTG). Each participant must have completed all required visits per protocol in the parent study AROAPOC3-3001 (NCT05089084), AROAPOC3-3003 (NCT06347003), AROAPOC3-3004 (NCT06347016) or AROAPOC3-3009 (NCT06347133). All eligible participants will receive plozasiran administered subcutaneously (SC) approximately every 3 months for 24 months. Participants will be counseled to remain on the specified low-fat diet throughout the study in accordance with local standard of care.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-02-07
• Study First Submitted QC: 2025-02-07
• Last Update Submitted: 2025-02-07
• Study First Posted: 2025-02-12
• Last Update Posted: 2025-02-12
• Study Start: 2025-03
• Primary Completion: 2028-07
• Study Completion: 2028-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 840

Inclusion Criteria

• Adult males, or nonpregnant (who do not plan to become pregnant), nonlactating adult females, who are able and willing to provide written informed consent prior to the performance of any study-specific procedures
• Completed all required study visits per protocol in the parent study AROAPOC3-3001, AROAPOC3-3003, AROAPOC3-3004 or AROAPOC3-3009
• Female subjects of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 90 days after the End of Study (EOS) or the last dose of plozasiran, whichever is later. Male subjects must agree to use a condom during the study and for at least 90 days after the EOS or last dose of plozasiran whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days after the EOS or last dose of plozasiran, whichever is later. Female subjects of childbearing potential on hormonal contraceptives must be stable on medication for >1 menstrual cycle prior to Day 1.

Exclusion Criteria

• Subject was permanently discontinued from receiving plozasiran in the parent study due to elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or due to HbA1c elevation that did not respond to antidiabetic regimen
• Subject withdrew consent for continued study treatment in the parent study
• Known hypersensitivity to the active substance or to any of the excipients of plozasiran
• Any new condition or worsening of existing condition or any other situation that in the Investigator's judgment, would make the subject unsuitable for enrollment, could interfere with the subject participating in or completing the study, would make it difficult to comply with protocol requirements, or put the subject at an additional safety risk
• Unwilling to limit alcohol consumption to within moderate limits for the duration of the study.

Note: Other inclusion/exclusion criteria may apply per protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Plozasiran Injection	Plozasiran Injection	8 doses of plozasiran (ARO-APOC3) administered by subcutaneous (SC) injection

Primary Outcome Measures

Name	Time	Method
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	From first dose of study drug through Month 24

Secondary Outcome Measures

Name	Time	Method
Percent Change from Baseline Over Time in Fasting LDL-C using Ultracentrifugation	From first dose of study drug through Month 24
Number of Participants With Emergent Apheresis	From first dose of study drug through Month 24
Change from Baseline Over Time in Fasting Serum Triglyceride (TG) Levels	From first dose of study drug through Month 24
Percent Change from Baseline Over Time in Fasting Serum TG Levels	From first dose of study drug through Month 24
Change from Baseline Over Time in Apolipoprotein CIII (APOC3)	From first dose of study drug through Month 24
Change from Baseline Over Time in Fasting Total Apolipoprotein B (Apo B)	From first dose of study drug through Month 24
Percent Change from Baseline Over Time in APOC3	From first dose of study drug through Month 24
Percent Change from Baseline Over Time in Remnant Cholesterol	From first dose of study drug through Month 24
Change from Baseline Over Time in Fasting Non-High-Density Lipoprotein Cholesterol (non-HDL-C)	From first dose of study drug through Month 24
Change from Baseline Over Time in Remnant Cholesterol	From first dose of study drug through Month 24
Adjudicated Major Adverse Cardiovascular Event Rates During the Treatment Period	From first dose of study drug through Month 24
Percent Change from Baseline Over Time in Fasting non-HDL-C	From first dose of study drug through Month 24
Change from Baseline Over Time in Fasting High-Density Lipoprotein Cholesterol (HDL-C)	From first dose of study drug through Month 24
Percent Change from Baseline Over Time in Fasting HDL-C	From first dose of study drug through Month 24
Percent Change from Baseline Over Time in Fasting Total Apo B	From first dose of study drug through Month 24
Change from Baseline Over Time in Fasting Low-Density Lipoprotein Cholesterol (LDL-C) using Ultracentrifugation	From first dose of study drug through Month 24
Change from Baseline Over Time in Hemoglobin A1c (HbA1c)	From first dose of study drug through Month 24
Titers of ADA to Plozasiran Over Time	From first dose of study drug through Month 24
Incidence of Anti-Drug Antibodies (ADA) to Plozasiran Over Time	From first dose of study drug through Month 24