Clinical trial NCT06822790: Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia
Official title: A Phase 3 Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia (SHASTA-10 Study)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hypertriglyceridemia
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2025-02-12
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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