Study to Evaluate Plozasiran in Adults with Severe Hypertriglyceridemia (SHASTA 3 Study)
Phase 3
Active, not recruiting
- Conditions
- Severe hypertriglyceridemia (SHTG)
- Registration Number
- 2023-509300-14-00
- Lead Sponsor
- Arrowhead Pharmaceuticals Inc.
- Brief Summary
To demonstrate the efficacy of plozasiran on reducing fasting serum TG levels
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 446
Inclusion Criteria
- Males, or nonpregnant (who do not plan to become pregnant) nonlactating females, who are ≥18 years of age at screening
- Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥ 500 mg/dL (≥5.65mmol/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%
- 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 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
- 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
- Acute pancreatitis within 4 weeks prior to screening
- 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 (V10 and V11) compared to placebo Percent change in fasting serum TG levels from baseline to Month 12 (V10 and V11) compared to placebo
- 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 <500 mg/dL (<5.65 mmol/L) at Month 12 Compared to Placebo Baseline, Month 12 Proportion of Participants 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 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 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 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 Change and/or percent change from baseline to Month 12 in liver fat content using MRI-PDFF, only in a subset of subjects Baseline, Month 12
Trial Locations
- Locations (196)
National Institute of Clinical Research
🇺🇸Garden Grove, California, United States
Orange County Research Center
🇺🇸Lake Forest, California, United States
Catalina Research Institute
🇺🇸Montclair, California, United States
Velocity Clinical Research, Panorama City
🇺🇸Panorama City, California, United States
The Cardiovascular Center
🇺🇸Redding, California, United States
Legacy Clinical Trials
🇺🇸Colorado Springs, Colorado, United States
Neoclinical Research
🇺🇸Hialeah, Florida, United States
East Coast Institute for Research, LLC
🇺🇸Lake City, Florida, United States
Panax Clinical Research
🇺🇸Miami Lakes, Florida, United States
Adult Medicine of Lake County
🇺🇸Mount Dora, Florida, United States
Scroll for more (186 remaining)National Institute of Clinical Research🇺🇸Garden Grove, California, United States