Study of Plozasiran (ARO-APOC3) in Adults With Severe Hypertriglyceridemia
- Conditions
- Severe Hypertriglyceridemia
- Interventions
- Drug: Plozasiran InjectionDrug: Placebo
- Registration Number
- NCT06347003
- Lead Sponsor
- Arrowhead Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 405
- 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 ≤8.5%
- Willing to follow diet counseling and maintain a stable low-fat diet
- Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)
- 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
- Arm && Interventions
Group Intervention Description Plozasiran Injection Plozasiran Injection 4 doses of plozasiran (ARO-APOC3) by subcutaneous (sc) injection Placebo Placebo calculated volume to match active treatment by sc injection
- Primary Outcome Measures
Name Time Method Percent Change in Fasting Serum Triglyceride (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 Participants Who Achieve Fasting TG Levels of <500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12 Compared to Placebo Month 10, 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 Proportion of Participants Who Achieve Fasting TG Levels of <150 mg/dL (<1.69 mmol/L) at Month 10 and Month 12 Compared to Placebo Month 10, 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 Hemoglobin A1c (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 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 Incidence Rates of 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 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
Trial Locations
- Locations (68)
Nova Scotia Health Authority
🇨🇦Halifax, Canada
Yuncheng Central Hospital
🇨🇳Yuncheng, Shanxi, China
East Coast Institute for Research, LLC
🇺🇸Lake City, Florida, United States
East Coast - Institute for Research
🇺🇸Macon, Georgia, United States
Methodist Physicians Clinic Heart Consultants
🇺🇸Omaha, Nebraska, United States
Gonzalez Research Institute
🇺🇸Houston, Texas, United States
Houston Methodist Hospital Department of Medicine Research
🇺🇸Houston, Texas, United States
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
Panax Clinical Research
🇺🇸Miami Lakes, Florida, United States
Adult Medicine of Lake County
🇺🇸Mount Dora, Florida, United States
Florida Institute for Clinical Research
🇺🇸Orlando, Florida, United States
Baptist Hospital Cardiology
🇺🇸Pensacola, Florida, United States
TBC Research
🇺🇸Tamarac, Florida, United States
R & B Medical Center
🇺🇸Tampa, Florida, United States
Meridian Clinical Research
🇺🇸Savannah, Georgia, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Ascension Saint Agnes Heart care
🇺🇸Baltimore, Maryland, United States
Elite Clinical Research Center
🇺🇸Flint, Michigan, United States
Olive Branch Family Medical Centre
🇺🇸Olive Branch, Mississippi, United States
Jefferson City Medical Group
🇺🇸Jefferson City, Missouri, United States
St. Louis Heart and Vascular
🇺🇸Saint Louis, Missouri, United States
Midwest Regional Health Services LLC
🇺🇸Omaha, Nebraska, United States
Santa Rosa Medical Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
CHEAR Center LLC
🇺🇸Bronx, New York, United States
Endocrine Associates of West Village
🇺🇸Long Island City, New York, United States
Vestal Velocity Clinical Research
🇺🇸Vestal, New York, United States
Carteret Medical Group
🇺🇸Morehead City, North Carolina, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Lynn Institute of Norman
🇺🇸Norman, Oklahoma, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Cardiovascular Research Center of Knoxville
🇺🇸Powell, Tennessee, United States
Dr. David Turbay MD PLLC
🇺🇸El Paso, Texas, United States
Baylor College of Medicine-Center for Cardiometabolic Disease Prevention
🇺🇸Houston, Texas, United States
Synergy Groups Medical LLC
🇺🇸Houston, Texas, United States
Clinical Trial Network LLC
🇺🇸Houston, Texas, United States
PlanIt Research PLLC
🇺🇸Houston, Texas, United States
Endocrine and Psychiatry Center
🇺🇸Houston, Texas, United States
Andres Garcia Zuniga MD PA
🇺🇸Laredo, Texas, United States
Synergy Groups Medical
🇺🇸Missouri City, Texas, United States
Stryde Research
🇺🇸Plano, Texas, United States
VIP Trials
🇺🇸San Antonio, Texas, United States
Discovery Clinical Services
🇨🇦Victoria, British Columbia, Canada
Centricity Research Brampton Endocrinology
🇨🇦Brampton, Ontario, Canada
Bluewater Clinical Research Group Inc.
🇨🇦Sarnia, Ontario, Canada
Clinical Research Solutions Inc.
🇨🇦Waterloo, Ontario, Canada
Institut de Recherches Cliniques de Montréal
🇨🇦Montréal, Quebec, Canada
Clinique des Maladies Lipidiques de Québec
🇨🇦Québec, Quebec, Canada
UMHAT "Pulmed" OOD
🇧🇬Plovdiv, Bulgaria
MHAT Sv. Sofia, OOD
🇧🇬Sofia, Bulgaria
UMHAT Sveta Ekaterina
🇧🇬Sofia, Bulgaria
UMHAT Kaspela, EOOD
🇧🇬Plovdiv, Bulgaria
Paratus Clinical Research Western Sydney
🇦🇺Blacktown, New South Wales, Australia
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Hunter Diabetes Centre and Aim Centre
🇦🇺Merewether, New South Wales, Australia
Eastern Clinical Research Unit - Endocrinology
🇦🇺Box Hill, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
De Meulemeester, Marc
🇧🇪Gozée, Belgium
AZ Sint-Maarten
🇧🇪Mechelen, Belgium
Respisom
🇧🇪Namur, Belgium
BVBA Dr. Luc Capiau
🇧🇪Wetteren, Belgium
Medical Center Medconsult Pleven OOD
🇧🇬Pleven, Bulgaria
MHAT Heart and Brain
🇧🇬Pleven, Bulgaria