Study of Plozasiran in Adults With Severe Hypertriglyceridemia
- Conditions
- Severe Hypertriglyceridemia
- Interventions
- Drug: Placebo
- Registration Number
- NCT06347016
- 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
- 300
- 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 ≤8.5%
- 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 (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
- 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 Proportion of Subjects Who Achieve Fasting TG Levels of < 500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12 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 Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo Baseline, Month 10 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 Subjects Receiving Plozasiran Over Time Through Month 12 From first dose of study drug through Month 12 Proportion of Subjects Who Achieve Fasting TG Levels of <150mg/dL (<1.69 mmol/L) at Month 10 and Month 12 Compared to Placebo Month 10, 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 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
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
Cardiovascular Center of Sarasota Foundation for Research and Education
🇺🇸Sarasota, Florida, United States
Georgia Clinical Research, LLC
🇺🇸Lawrenceville, 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 and Vascular Specialists
🇺🇸Overland Park, Kansas, United States
Cotton-O'Neil Clinical Research Center, Stormont-Vail West
🇺🇸Topeka, Kansas, United States
Southern Clinical Research Associates
🇺🇸Metairie, Louisiana, United States
Annapolis Internal Medicine
🇺🇸Annapolis, Maryland, United States
Elite Clinical Research
🇺🇸Jackson, Mississippi, United States
Methodist Physicians Clinic
🇺🇸Fremont, Nebraska, United States
Velocity Clinical Research
🇺🇸Norfolk, Nebraska, United States
Overlook Medical Center
🇺🇸Morristown, New Jersey, United States
Jack D. Weiler Hospital
🇺🇸Bronx, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Northwell Health Physician Partners at Peconic
🇺🇸Riverhead, New York, United States
Triad Internal Medicine
🇺🇸Asheboro, North Carolina, United States
Wilmington Health
🇺🇸Wilmington, North Carolina, United States
Internal Medicine Care Beavercreek
🇺🇸Beavercreek, Ohio, United States
OhioHealth Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
AMS Cardiology
🇺🇸Horsham, Pennsylvania, United States
Capital Area Research, LLC
🇺🇸Newport, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Piedmont Research Partners
🇺🇸Fort Mill, South Carolina, United States
Tribe Clinical Research
🇺🇸Greenville, South Carolina, United States
University Diabetes & Endocrine Consultants
🇺🇸Chattanooga, Tennessee, United States
Diabetes and Thyroid Center of Fort Worth
🇺🇸Fort Worth, Texas, United States
Juno Research LLC
🇺🇸Houston, Texas, United States
Care and Cure Clinic
🇺🇸Houston, Texas, United States
Spring Clinical Research
🇺🇸Houston, Texas, United States
Sugar Lakes Family Practice
🇺🇸Sugar Land, Texas, United States
Northwest Houston Clinical Research, PLLC
🇺🇸Tomball, Texas, United States
Crossroads Clinical Research
🇺🇸Victoria, Texas, United States
Cope Family Medicine
🇺🇸Bountiful, Utah, United States
Chrysalis Clinical Research
🇺🇸Saint George, Utah, United States
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
Roanoke Heart Institute
🇺🇸Roanoke, Virginia, United States
Expertia S.A- Mautalen Salud e Investigación
🇦🇷Caba, Buenos Aires, Argentina
CINME - Centro De Investigaciones Metabolicas
🇦🇷Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Centro Medico Colon
🇦🇷Córdoba, Cordoba, Argentina
CIPADI Centro Integral de Prevención y Atención en Diabetes
🇦🇷Godoy Cruz, Mendoza, Argentina
Instituto Medico Fundación Grupo Colaborativo Rosario Investigación y Prevención Medica
🇦🇷Rosario, Santa FE, Argentina
Hospital Cardio Pulmonar
🇧🇷Salvador, Bahia, Brazil
CECAP - Centro de Cardiologia Clínica
🇧🇷Brasília, Distrito Federal, Brazil
CARDRESEARCH - Cardiologia Assistencial
🇧🇷Belo Horizonte, Minas Gerais, Brazil
IPECC - Instituto de Pesquisa Clínica de Campinas
🇧🇷Campinas, Sao Paulo, Brazil
Pesquisare Saúde
🇧🇷Santo André, Sao Paulo, Brazil
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
🇧🇷São José Do Rio Preto, Sao Paulo, Brazil
Centro de Pesquisa Clinica do Coracao
🇧🇷Aracaju, Sergipe, Brazil
Hospital Agamenon Magalhães
🇧🇷Recife, Brazil
MHAT Yuliya Vrevska - Byala, EOOD
🇧🇬Byala, Bulgaria
Medical Center Diamedical - 2013 OOD
🇧🇬Dimitrovgrad, Bulgaria
MHAT-Haskovo AD
🇧🇬Haskovo, Bulgaria
Medical Center Hera - Kyustendil EOOD
🇧🇬Kyustendil, Bulgaria
Medical Center Rusemed EOOD
🇧🇬Ruse, Bulgaria
Medical Center Unimed EOOD
🇧🇬Sevlievo, Bulgaria
Second medical center - Sofia ЕOOD
🇧🇬Sofia, Bulgaria
Medical Center Acad. I. Penchev, EOOD
🇧🇬Sofia, Bulgaria
UMHAT Alexandrovska EAD
🇧🇬Sofia, Bulgaria
Medical Center Hera EOOD
🇧🇬Sofia, Bulgaria
Medical Center Sv. Dimitar
🇧🇬Sofia, Bulgaria
Kalimat"-M.C.
🇧🇬Sofia, Bulgaria
UMHAT SofiaMed, OOD
🇧🇬Sofia, Bulgaria
Medical Center ZARA-MED EOOD
🇧🇬Stara Zagora, Bulgaria
Medical Arts Health Research Group
🇨🇦North Vancouver, British Columbia, Canada
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
Centre de Recherche Clinique de Laval
🇨🇦Laval, Quebec, Canada
Recherche Clinique Sigma Inc
🇨🇦Québec, Quebec, Canada
Centre de Medecine Metabolique de Lanaudiere
🇨🇦Terrebonne, Quebec, Canada
Fakultni nemocnice u svate Anny v Brne
🇨🇿Brno, Czechia
EDUMED s.r.o.
🇨🇿Náchod, Czechia
PreventaMed s.r.o.
🇨🇿Olomouc, Czechia
MUDr. Jan KVASNIČKA,CSc. Angiologie kardiologie a interna
🇨🇿Praha, Czechia
Nemocnice Slany
🇨🇿Slaný, Czechia
Unilabs Diagnostics, k.s
🇨🇿Teplice, Czechia
Kardiologicka ambulance MUDr. Ferkl s.r.o.
🇨🇿Trutnov, Czechia
Assistance Publique Hopitaux de Marseille AP HM Hopital de La Conception
🇫🇷Marseille, Bouches-du-Rhône, France
Groupe Hospitalier Sud Hôpital Haut-Lévêque
🇫🇷Pessac, Gironde, France
Centre Hospitalier de la côte Basque
🇫🇷Bayonne, Pyrenees Atlantiques, France
Hopital Saint Joseph Saint Luc
🇫🇷Lyon, Rhone, France
APHP Hôpital Universitaire Pitié Salpêtrière
🇫🇷Paris, France
MVZ Jung GbR
🇩🇪Deggingen, Baden Wuerttemberg, Germany
Gemeinschaftspraxis Dr. Josef Grosskopf und Dr. Wilma Grosskopf
🇩🇪Wallerfing, Bayern, Germany
SMO.MD GmbH
🇩🇪Magdeburg, Sachsen Anhalt, Germany
Charité - Campus Charité Mitte
🇩🇪Berlin, Germany
Belgyogyaszati es Kardiologiai Maganrendelo
🇭🇺Békéscsaba, Hungary
Obudai Egeszsegugyi Centrum Kft.
🇭🇺Kaposvár, Hungary
IPR Hungary Kft.
🇭🇺Miskolc, Hungary
COROMed-SMO Kft.
🇭🇺Pécs, Hungary
Da Vinci Maganklinika
🇭🇺Pécs, Hungary
Belvarosi Egeszseghaz Kft.
🇭🇺Zalaegerszeg, Hungary
Medical Centre OLVI
🇱🇻Daugavpils, Latvia
Daugavpils Regional Hospital
🇱🇻Daugavpils, Latvia
Department of Internal Medicine, Daugavpils Regional Hospital
🇱🇻Daugavpils, Latvia
Dr. R. Eglites Private practice
🇱🇻Kuldīga, Latvia
Pauls Stradins Clinical University Hospital SLLC
🇱🇻Riga, Latvia
Riga East Clinical University Hospital
🇱🇻Riga, Latvia
Medical Centre DAP
🇱🇻Riga, Latvia
Inese Petrova General Practitioner Practice
🇱🇻Tukums, Latvia
Kaunas City Polyclinic, Silainiai Subdivision
🇱🇹Kaunas, Lithuania
Klinikiniai sprendimai, JSC
🇱🇹Kaunas, Lithuania
Inmedica, JSC
🇱🇹Kaunas, Lithuania
Centre of Cardiology and Angiology, Vilnius University Hospital
🇱🇹Vilnius, Lithuania
Vilnius University Hospital Santaros Klinikos, Public Institution
🇱🇹Vilnius, Lithuania
Pirmoji Viltis, JSC
🇱🇹Šiauliai, Lithuania
New Zealand Clinical Research (NZCR)
🇳🇿Christchurch, New Zealand
Te Whatu Ora Taranaki
🇳🇿New Plymouth, New Zealand
Wellington Regional Hospital
🇳🇿Newtown, New Zealand
MICS Centrum Medyczne Bydgoszcz
🇵🇱Bydgoszcz, Poland
Centrum Medyczne Pratia Gdynia
🇵🇱Gdynia, Poland
Clinical Medical Research Sp. z o.o.
🇵🇱Katowice, Poland
Centrum Badawcze Panaceum Agnieszka Brzezicka, Magdalena Lenkiewicz Sp z o.o.
🇵🇱Malbork, Poland
Twoja Przychodnia-Szczecinskie Centrum Medyczne Sp. z o. o.
🇵🇱Szczecin, Poland
Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
🇵🇱Toruń, Poland
NZOZ Zdrowie s.c. Agnieszka i Donald Drożdż
🇵🇱Wrocław, Poland
Velocity Zamosc
🇵🇱Zamość, Poland
Indywidualna Specjalistyczna Praktyka Lekarska
🇵🇱Łódź, Poland
Kardiovaskularne centrum, s.r.o.
🇸🇰Bratislava, Slovakia
Kardiologická ambulancia Cardioamb s.r.o
🇸🇰Nové Zámky, Slovakia
Medispol s.r.o.
🇸🇰Prešov, Slovakia
Tatratrial s.r.o.
🇸🇰Rožňava, Slovakia
Dr IO Ebrahim Inc
🇿🇦Centurion, Gauteng, South Africa
DJW Navorsing
🇿🇦Krugersdorp, Gauteng, South Africa
RYEXO Clinical Research
🇿🇦Pretoria, Gauteng, South Africa
Dr. Jeevren Reddy's surgery
🇿🇦Durban, KwaZulu-Natal, South Africa
Canal Walk Medical and Wellness Centre
🇿🇦Cape Town, Western Cape, South Africa
Corbod Research
🇿🇦Cape Town, Western Cape, South Africa
Langeberg Clinical Trials
🇿🇦Cape Town, Western Cape, South Africa
Tiervlei Trial Centre
🇿🇦Cape Town, Western Cape, South Africa
UCT Lipid Laboratory
🇿🇦Cape Town, Western Cape, South Africa
Eden Heart
🇿🇦Mossel Bay, Western Cape, South Africa
Tsitsikamma Clinical Research Initiative
🇿🇦Plettenberg Bay, Western Cape, South Africa
Dr JM Engelbrecht Trial Site
🇿🇦Somerset West, Western Cape, South Africa
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, La Coruña, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain