Study to Evaluate Plozasiran in Adults with Severe Hypertriglyceridemia (SHASTA-4 Study)

Phase 3

Active, not recruiting

• Conditions: Severe hypertriglyceridemia (SHTG)

• Registration Number: 2023-509301-80-00
• Lead Sponsor: Arrowhead Pharmaceuticals Inc.

Brief Summary

To demonstrate the efficacy of plozasiran on reducing fasting serum TG levels

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: 2024-07-23
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-18
• Last Update Posted: 2025-07-23
• Primary Completion: 2026-06
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 311

Inclusion Criteria

• Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥500 mg/dL (≥5.65 mmol/L)
• Mean fasting TG level ≥500 mg/dL (≥5.65 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 ≤9.0%
• Must be on standard of care lipid-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 to a previous adverse reaction associated with, attributed to, or caused by specific drug)

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 (except inclisiran, which is permitted)
• Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1 Hyperlipoproteinemia) by documentation of confirmed homozygote or double heterozygote for loss-of-function mutations in type 1- causing genes
• Body mass index >45kg/m^2

Note: Additional Inclusion/Exclusion criteria may apply per protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Percent change in fasting serum 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 subjects who achieve fasting TG levels of <500 mg/dL (<5.65 mmol/L) at Month 12 compared to placebo	Baseline, Month 12
Proportion of Subjects Who Achieve Fasting TG Levels of < 150 mg/dL (<1.69 mmol/L) at Month 12 compared to placebo	Baseline, Month 12
Percent change in remnant cholesterol (VLDL-C) from baseline to Month 12 compared to placebo	Baseline, Month 12
Percent change in non-HDL-C from baseline to Month 12 compared to placebo	Baseline, Month 12
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	Month 12
Number of Subjects 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 Impaired Glucose Tolerance 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) and Other Glycemic Control Parameters 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 Subjects 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 Subjects Receiving Plozasiran Over Time Through Month 12	From first dose of study drug through Month 12

Trial Locations

Locations (148)

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, Inc.; 🇺🇸 Huntington Beach, California, United States

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

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

FOMAT Medical Research; 🇺🇸 Oxnard, California, United States

Innovative Research of West Florida, Inc.; 🇺🇸 Clearwater, Florida, United States

Harmony Clinical Research; 🇺🇸 North Miami, Florida, United States

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