Phase 3 Study of Plozasiran in Adults With Hypertriglyceridemia

Phase 3

Recruiting

• Conditions: Hypertriglyceridemia
• Interventions: Drug: Placebo; Drug: Plozasiran Injection

• Registration Number: NCT06347133
• 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 hypertriglyceridemia (HTG). 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.

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: 2024-05-21
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-25
• Last Update Posted: 2024-11-27
• Primary Completion: 2026-07
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1328

Inclusion Criteria

• Established diagnosis of hypertriglyceridemia (HTG) and prior documented evidence (medical history) of mean fasting TG level ≥150 mg/dL (≥1.69 mm/L) and ≤499 mg/dL (≤5.64 mmol/L)
• Mean fasting TG level ≥150 mg/dL (≥1.69 mmol/L) and ≤499 mg/dL (≤5.64 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)

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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
• Acute pancreatitis within 4 weeks prior to screening
• Body mass index >45 kg/m^2

Note: Additional Inclusion/Exclusion criteria may apply per protocol

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	calculated volume to match active treatment by sc injection
Plozasiran Injection	Plozasiran Injection	4 doses of plozasiran by subcutaneous (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 <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 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
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

Trial Locations

Locations (103)

IMC Diagnostic and Medical Clinic, LLC; 🇺🇸 Mobile, Alabama, United States

East Coast Institute for Research, LLC; 🇺🇸 Lake City, Florida, United States

Northwell Health Physician Partners at Peconic; 🇺🇸 Riverhead, New York, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Gonzalez Research Institute; 🇺🇸 Houston, Texas, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

Paratus Clinical Research, Western Sydney; 🇦🇺 Blacktown, New South Wales, Australia

The Aim Centre; 🇦🇺 Merewether, New South Wales, Australia

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Medical Center Hera - Kyustendil; 🇧🇬 Kyustendil, Bulgaria

MHAT Heart and Brain - Pleven; 🇧🇬 Pleven, Bulgaria

Medical Center Sv. Dimitar; 🇧🇬 Sofia, Bulgaria

MHAT Sv. Sofia, OOD; 🇧🇬 Sofia, Bulgaria

Medical Center ZARA-MED EOOD; 🇧🇬 Stara Zagora, Bulgaria

Nova Scotia Health Authority; 🇨🇦 Halifax, Canada

Clinical Medical Research Sp. z o.o.; 🇵🇱 Katowice, Poland

Indywidualna Specjalistyczna Praktyka Lekarska; 🇵🇱 Łódź, Poland

Ascension St. Vincents Birmingham; 🇺🇸 Birmingham, Alabama, United States

National Heart Institute; 🇺🇸 Beverly Hills, California, United States

Hope Clinical Research; 🇺🇸 Canoga Park, California, United States

National Institute of Clinical Research; 🇺🇸 Garden Grove, California, United States

National Institute of Clinical Research, Inc.; 🇺🇸 Huntington Beach, California, United States

Orange County Research Center, Inc.; 🇺🇸 Lake Forest, California, United States

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

Catalina Research Institute, LLC; 🇺🇸 Montclair, California, United States

Fomat Medical Research, Inc.; 🇺🇸 Oxnard, 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

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

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

Florida Institute for Clinical Research; 🇺🇸 Orlando, Florida, United States

Baptist Hospital Cardiology; 🇺🇸 Pensacola, Florida, United States

Cardiovascular Center of Sarasota Foundation for Research and Education; 🇺🇸 Sarasota, Florida, United States

TBC Research; 🇺🇸 Tamarac, Florida, United States

Georgia Clinical Research Center, Inc.; 🇺🇸 Lawrenceville, Georgia, United States

East Coast Institute For Research, LLC; 🇺🇸 Macon, Georgia, United States

Meridian Clinical Research, LLC; 🇺🇸 Savannah, Georgia, United States

RNA America Health Sciences; 🇺🇸 Sugar Hill, Georgia, United States

Midwest Cardiovascular Research and Education Foundation; 🇺🇸 Elkhart, Indiana, United States

Ascension St. Vincent Heart Center; 🇺🇸 Indianapolis, Indiana, United States

The South Bend Clinic LLC; 🇺🇸 South Bend, Indiana, United States

Midwest Heart & Vascular Specialists; 🇺🇸 Overland Park, Kansas, United States

Cotton-O'Neil Clinical Research Center, Stormont-Vail West; 🇺🇸 Topeka, Kansas, United States

Southern Clinical Research; 🇺🇸 Metairie, Louisiana, United States

Annapolis Internal Medicine; 🇺🇸 Annapolis, Maryland, United States

Ascension Saint Agnes Heart Care; 🇺🇸 Baltimore, Maryland, United States

Elite Clinical Research Center; 🇺🇸 Flint, Michigan, United States

Olive Branch Family Medical Center; 🇺🇸 Olive Branch, Mississippi, United States

Jefferson City Medical Group PC; 🇺🇸 Jefferson City, Missouri, United States

St. Louis Heart and Vascular; 🇺🇸 Saint Louis, Missouri, United States

Velocity Clinical Research; 🇺🇸 Norfolk, Nebraska, United States

Methodist Physicians Clinic Heart Consultants; 🇺🇸 Omaha, Nebraska, 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

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Velocity Clinical Research-Vestal New York; 🇺🇸 Vestal, New York, United States

Triad Internal Medicine; 🇺🇸 Asheboro, North Carolina, United States

Carteret Medical Group; 🇺🇸 Morehead City, North Carolina, United States

Wilmington Health; 🇺🇸 Wilmington, North Carolina, United States

Internal Medicine Care Inc; 🇺🇸 Beavercreek, Ohio, United States

OhioHealth Research Institute; 🇺🇸 Columbus, Ohio, United States

Lynn Institute of Norman; 🇺🇸 Norman, Oklahoma, United States

Lynn Health Science Institute East; 🇺🇸 Oklahoma City, Oklahoma, United States

Diabetes and Thyroid Center of Fort Worth; 🇺🇸 Fort Worth, Texas, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Juno Research LLC; 🇺🇸 Houston, Texas, United States

Lynn Health Sci. Inst.; 🇺🇸 Oklahoma City, Oklahoma, United States

Abington Medical Specialists, P.C.; 🇺🇸 Horsham, Pennsylvania, United States

Capital Area Research, LLC; 🇺🇸 Newport, Pennsylvania, United States

Piedmont Research Partners; 🇺🇸 Fort Mill, South Carolina, United States

Tribe Clinical Research, LLC; 🇺🇸 Greenville, South Carolina, United States

Cardiovascular Research Center of Knoxville; 🇺🇸 Powell, Tennessee, United States

David Turbay, MD, PLLC; 🇺🇸 El Paso, Texas, United States

Clinical Trial Network LLC; 🇺🇸 Houston, Texas, United States

PlanIt Research, PLLC; 🇺🇸 Houston, Texas, United States

Synergy Groups Medical LLC; 🇺🇸 Houston, Texas, United States

Spring Clinical Research; 🇺🇸 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

Sugar Lakes Family Practice; 🇺🇸 Sugar Land, Texas, United States

Northwest Houston Heart Center; 🇺🇸 Tomball, Texas, United States

Crossroads Clinical Research; 🇺🇸 Victoria, Texas, United States

Cope Family Medicine; 🇺🇸 Bountiful, Utah, United States

Chrysalis Clinical Research, LLC; 🇺🇸 Saint George, Utah, United States

Manassas Clinical Research Center; 🇺🇸 Manassas, Virginia, United States

Medical Arts Health Research Group; 🇨🇦 North Vancouver, British Columbia, Canada

Discovery Clinical Services Ltd.; 🇨🇦 Victoria, British Columbia, Canada

Centricity Research Brampton; 🇨🇦 Brampton, Ontario, Canada

Bluewater Clinical Research Group Inc.; 🇨🇦 Sarnia, Ontario, Canada

Clinical Research Solutions Inc.; 🇨🇦 Waterloo, Ontario, Canada

Ecogene-21; 🇨🇦 Chicoutimi, Quebec, Canada

Centre de Recherche Clinique de Laval; 🇨🇦 Laval, Quebec, Canada

Clinique des Maladies Lipidiques de Quebec; 🇨🇦 Québec, Quebec, Canada

Centre de Medicine Metabolique de Lanaudiere; 🇨🇦 Québec, Quebec, Canada

Recherche Clinique Sigma Inc; 🇨🇦 Quebec, Canada