nctId: NCT06347016 id: AROAPOC3-3004 id: 2023-509301-80 type: EUDRACT_NUMBER briefTitle: Study of Plozasiran in Adults With Severe Hypertriglyceridemia acronym: SHASTA-4 overallStatus: NOT_YET_RECRUITING date: 2024-05 date: 2026-07 date: 2026-10 date: 2024-04-04 date: 2024-04-16 name: Arrowhead Pharmaceuticals class: INDUSTRY briefSummary: This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). 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. After Month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol. conditions: Severe Hypertriglyceridemia studyType: INTERVENTIONAL phases: PHASE3 allocation: RANDOMIZED interventionModel: PARALLEL primaryPurpose: TREATMENT masking: QUADRUPLE whoMasked: PARTICIPANT whoMasked: CARE_PROVIDER whoMasked: INVESTIGATOR whoMasked: OUTCOMES_ASSESSOR count: 300 type: ESTIMATED name: Plozasiran Injection name: Placebo measure: Percent Change in Fasting Serum Triglyceride (TG) Levels from Baseline to Month 12 Compared to Placebo measure: Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo measure: Proportion of Subjects Who Achieve Fasting TG Levels of < 500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12 measure: Adjudicated Abdominal Clinical Event Rate (Including Emergency Room Visits or Hospitalizations for Abdominal Pain Attributed to Hypertriglyceridemia and Events of Documented Pancreatitis) During the Treatment Period Compared to Placebo at Month 12 measure: Proportion of Subjects Who Achieve Fasting TG Levels of <150mg/dL (<1.69 mmol/L) at Month 10 and Month 12 Compared to Placebo measure: Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) Over Time through Month 12 as Compared to Placebo measure: Incidence Rates of New-Onset Diabetes Mellitus (NODM) Throughout the Course of Treatment measure: Incidence Rates of Impaired Glucose Tolerance Throughout the Course of Treatment measure: Incidence Rates of Worsening of Existing Diabetes Throughout the Course of Treatment measure: Change from Baseline in Hemoglobin A1c (HbA1c) and Other Glycemic Control Parameters During the Treatment Period Compared to Placebo measure: Change from Baseline in Fasting Blood Glucose During the Treatment Period Compared to Placebo measure: Change from Baseline in C-Peptide During the Treatment Period Compared to Placebo measure: Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) During the Treatment Period Compared to Placebo measure: 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 measure: Initiation of New Medication for Hyperglycemia among Study Participants Not Known to Have Pre-existing Diabetes Mellitus During the Treatment Period Compared to Placebo measure: Adjudicated Major Adverse Cardiovascular Events (MACE) Rates During the Treatment Period Compared to Placebo measure: Incidence of Anti-drug Antibodies (ADA) to Plozasiran in Subjects Receiving Plozasiran Over Time Through Month 12 measure: Titers of Anti-drug Antibodies (ADA) to Plozasiran in Subjects Receiving Plozasiran Over Time Through Month 12 sex: ALL minimumAge: 18 Years stdAges: ADULT stdAges: OLDER_ADULT hasResults: False