A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia

Phase 3

Active, not recruiting

• Conditions: Severe Hypertriglyceridemia
• Interventions: Drug: Olezarsen; Drug: Placebo

• Registration Number: NCT05079919
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

The purpose of the study is to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

Detailed Description

This is a multi-center, randomized, double-blind, placebo-controlled study in 617 participants. Participants will be randomized to receive olezarsen or placebo in a 53-week treatment period. The length of participation in the study will be approximately 78 weeks, which includes an up to 12-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period or transition to open-label extension (OLE) study with up to 1-year treatment.

Study Timeline

• Study First Submitted: 2021-10-04
• Study First Submitted QC: 2021-10-04
• Study First Posted: 2021-10-15
• Study Start: 2021-10-25
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29
• Primary Completion: 2025-04
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 617

Inclusion Criteria

• Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification
• Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.

Key

Exclusion Criteria

• Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
• Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
• Total bilirubin > upper limit of normal unless due to Gilbert's syndrome
• Estimated GFR < 30 mL/min/1.73 m^2

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Olezarsen	Olezarsen	Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.
Placebo	Placebo	Olezarsen-matching placebo will be administered once every 4 weeks by SC injection from Week 1 through Week 49.

Primary Outcome Measures

Name	Time	Method
Percent Change from Baseline in Fasting TG Compared to Placebo	Baseline and Month 6

Secondary Outcome Measures

Name	Time	Method
Percent Change from Baseline in Fasting TG Compared to Placebo	Baseline and Month 12
Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III), Remnant Cholesterol and Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Compared to Placebo	Baseline, Month 6 and 12
Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) Compared to Placebo in the Subgroup of Participants with Baseline TG ≥ 880 mg/dL	Month 12
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo	Week 1 through Week 53
Proportion of Patients Who Achieve Fasting TG <500 mg/dL (5.65 mmol/L) Compared to Placebo	Month 12
Absolute Change in Hepatic Fat Fraction (HFF) Between Olezarsen Treatment Group and Pooled Placebo	Baseline through Month 12

Trial Locations

Locations (201)

Excel Medical Clinical Trials, LLC; 🇺🇸 Boca Raton, Florida, United States

Dr Jan Engelbrecht and Ass. Inc; 🇿🇦 Cape Town, Western Cape, South Africa

Albert Schweitzer ziekenhuis; 🇳🇱 Dordrecht, Netherlands

Palm Research Center, INC.; 🇺🇸 Las Vegas, Nevada, United States

Oak Tree Surgery and Pensilva Health Centre; 🇬🇧 Liskeard, Cornwall, United Kingdom

Panthera Biopartners; 🇬🇧 Sheffield, England, United Kingdom

Lakeside Healthcare at Corby; 🇬🇧 Corby, Northamptonshire, United Kingdom

Human-Care s.r.o.; 🇸🇰 Košice, Slovakia

Centro Hospitalar Universitário de São João Consultas Externas de Endocrinologia K13; 🇵🇹 Porto, Portugal

Centro Hospitalar; 🇵🇹 Vila Nova De Gaia, Portugal

Nemocnica s poliklinikou Brezno; 🇸🇰 Brezno, Slovakia

Vychodoslovensky Ustav srdcovych a cievnych chorob a.s.; 🇸🇰 Kosice, Slovakia

Nemocnica arm. generala L. Svobodu Svidnik,; 🇸🇰 Svidnik, Slovakia

Gabriela Zhelyazkova; 🇧🇬 Sliven, Bulgaria

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

UMHAT Prof. Dr. Stoyan Kirkovich AD, Clinic of Cardiology; 🇧🇬 Stara Zagora, Bulgaria

SHAT "Special Medic" Ltd; 🇧🇬 Plovdiv, Bulgaria

Wake Forest University Health Sciences; 🇺🇸 Salem, North Carolina, United States

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

CRU Hungary Kft; 🇭🇺 Borsod, Hungary

University of California, San Diego (UCSD); 🇺🇸 La Jolla, California, United States

Ocala Cardiovascular Research; 🇺🇸 Ocala, Florida, United States

Southeast Clinical Research LLC; 🇺🇸 Chiefland, Florida, United States

Affinity Health; 🇺🇸 Oak Brook, Illinois, United States

IMA Clinical Research Chicago; 🇺🇸 Chicago, Illinois, United States

IMA Clinical Research; 🇺🇸 Saint Louis, Missouri, United States

Continental Clinical Solutions; 🇺🇸 Towson, Maryland, United States

Hudson County Clinical Trials Research Center; 🇺🇸 Union City, New Jersey, United States

Modern Medical; 🇺🇸 Syosset, New York, United States

Medical Center Doctor Staykov EOOD; 🇧🇬 Burgas, Bulgaria

Cone Medical Center; 🇺🇸 Greensboro, North Carolina, United States

The Miriam Hospital; 🇺🇸 Providence, Rhode Island, United States

Modern Medicine; 🇺🇸 Brooklyn, New York, United States

Aventiv Research; 🇺🇸 Columbus, Ohio, United States

Health Concepts; 🇺🇸 Rapid City, South Dakota, United States

NYU Langone; 🇺🇸 New York, New York, United States

Hightower Clinical Trial Services; 🇺🇸 Oklahoma City, Oklahoma, United States

York Clinical Research LLC; 🇺🇸 Norfolk, Virginia, United States

MHAT Blagoevgrad AD; 🇧🇬 Blagoevgrad, Bulgaria

Medical Center "Hera" EOOD; 🇧🇬 Montana, Bulgaria

Medical Center Rusemed EOOD; 🇧🇬 Ruse, Bulgaria

DCC 1 Sliven; 🇧🇬 Sliven, Bulgaria

Medical Centar "KALIMAT"; 🇧🇬 Sofia, Bulgaria

Medical Centre Nevromedics EOOD; 🇧🇬 Veliko Tarnovo, Bulgaria

Fakultni nemocnice Ostrava; 🇨🇿 Ostrava, Czechia

UMHAT Sofiamed OOD; 🇧🇬 Sofia, Bulgaria

Canadian Phase Onward Inc; 🇨🇦 Toronto, Ontario, Canada

Medical Center Endomedical EOOD; 🇧🇬 Sofia, Bulgaria

New Rehabilitation Center; 🇧🇬 Stara Zagora, Bulgaria

Arc Biosystems; 🇨🇦 Vancouver, British Columbia, Canada

Centro Hospitalar do Baixo Vouga Hospital Infante D. Pedro; 🇵🇹 Aveiro, Portugal

CHU Nantes - Hopital Nord Laennec; 🇫🇷 Saint-Herblain, France

Fakultní nemocnice Hradec Králové; 🇨🇿 Hradec Králové, Czechia

Borbanya Praxis Eü KFT; 🇭🇺 Nyíregyháza, Hungary

DRC Gyogyszervizsgalo Kozpont Kft; 🇭🇺 Veszprém, Hungary

Salvia; 🇵🇱 Katowice, Poland

Futuremeds sp. z o.o; 🇵🇱 Wroclaw, Poland

Centro Hospitalar e Universitário de Coimbra, EPE; 🇵🇹 Coimbra, Portugal

Ziekenhuis Gelderse Vallei; 🇳🇱 Ede, Netherlands

ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Italy

CHU Dijon Bourgogne; 🇫🇷 Dijon, France

Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore; 🇮🇹 Roma, Italy

Klinische Forschung Hamburg GmbH; 🇩🇪 Hamburg, Germany

Clinica Universidad de Navarra; 🇪🇸 Madrid, Spain

Ylitornio Health Care Center; 🇫🇮 Ylitornio, Finland

Hacettepe University Medical Faculty; 🇹🇷 Ankara, Turkey

Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Iatros International; 🇿🇦 Bloemfontein, Free State, South Africa

Hopital de la Conception; 🇫🇷 Marseille, France

Hospital Universitario Reina Sofia; 🇪🇸 Córdoba, Spain

Universitaetsklinikum Carl Gustav Carus an der TU Dresden; 🇩🇪 Dresden, Germany

Uniklinik Köln; 🇩🇪 Köln, Germany

Kaplan Medical Center; 🇮🇱 Reẖovot, Israel

ClinMedica Research Sp.z o.o.; 🇵🇱 Skierniewice, Poland

Hospital Egas Moniz - Centro Hospitalar de Lisboa Ocidental; 🇵🇹 Lisbon, Portugal

Academic Medical Center - Department of Vascular Medicine; 🇳🇱 Amsterdam, Netherlands

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands

Sandwell General Hospital; 🇬🇧 Lyne, West Bromwich, United Kingdom

Auckland City Hospital; 🇳🇿 Grafton, Auckland, New Zealand

BKS Research Kft; 🇭🇺 Hatvan, Heves, Hungary

Medifarma 98 Kft; 🇭🇺 Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary

Policlinico Umberto; 🇮🇹 Roma, Italy

Debreceni Egyetem Klinikai Kozpont Belgyogyaszat A epulet; 🇭🇺 Debrecen, Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz; 🇭🇺 Szekesfehervar, Hungary

Kardiologische Praxis in Papenburg; 🇩🇪 Papenburg, Germany

Lipid Clinic; 🇳🇴 Oslo, Norway

Praktyka Lekarska Ewa Krzyzagorska; 🇵🇱 Poznan, Poland

Instytut Centrum Zdrowia Matki Polki Klinika; 🇵🇱 Łódz, Poland

Rijnstate Arnhem; 🇳🇱 Arnhem, Netherlands

Radboud UMC; 🇳🇱 Nijmegen, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

St. Josefskrankenhaus,; 🇩🇪 Heidelberg, Germany

Lady Davis Carmel Medical Center; 🇮🇱 Haifa, Israel

Semmelweis Egyetem Kardiológiai Rehabilitacio; 🇭🇺 Budapest, Hungary

Sheba Medical Center; 🇮🇱 Tel HaShomer, Israel

IPR Hungary Kft.; 🇭🇺 Miskolc, Hungary

New Zealand Clinical Research; 🇳🇿 Christchurch, New Zealand

IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di SantOrsola; 🇮🇹 Bologna, Italy

Ospdale E. Bassini; 🇮🇹 Milano, Italy

SOROKA Medical Center; 🇮🇱 Be'er Sheva, Israel

Észak-Pesti Centrumkórház - Honvédkórház; II. Belgyógyászati Osztály; 🇭🇺 Budapest, Hungary

Unitas Hospital; 🇿🇦 Centurion, Gauteng, South Africa

Bnai Zion Medical Center; 🇮🇱 Haifa, Israel

Institut d'Investigació i Innovació Parc Taulí (I3PT) Departament Medicina Universitat; 🇪🇸 Barcelona, Spain

Osrodek Badan Klinicznych Metabolica; 🇵🇱 Tarnów, Poland

Hospital Universitari de Bellvitge; 🇪🇸 Barcelona, Spain

Hospital Universitario; 🇪🇸 Madrid, Spain

Wellington Regional Hospital; 🇳🇿 Newtown, New Zealand

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel

Turku University Hospital; 🇫🇮 Turku, Finland

Belinus BT; 🇭🇺 Debrecen, Hungary

Praxis Dr. med. Taggeselle; 🇩🇪 Markkleeberg, Germany

Vseobecna fakultni nemocnice; 🇨🇿 Prague, Czechia

Stoffwechselcentrum Charite Campus Virchow; 🇩🇪 Berlin, Germany

Institut de recherches cliniques de Montréal (IRCM); 🇨🇦 Montréal, Quebec, Canada

Rabin Medical Center; 🇮🇱 Petach Tikva, Israel

MEDICUS SERVICES s.r.o.; 🇨🇿 Brandýs Nad Labem, Czechia

Hôpital Louis Pradel; 🇫🇷 Bron, France

Lekarna Poliklinika Hurka; 🇨🇿 Prague, Czechia

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Godstrup Regional Hospital; 🇩🇰 Herning, Denmark

A.O. Policlinico Universitario P. Giaccone; 🇮🇹 Palermo, Italy

Ege University School of Medicine, Department of Cardiology; 🇹🇷 İzmir, Turkey

Necmettin Erbakan University Meram Medical Faculty; 🇹🇷 Konya, Turkey

CHU Montpellier - Hôpital Lapeyronie; 🇫🇷 Montpellier, France

Hopital Pitie Salpetriere APHP; 🇫🇷 Paris, France

Waterloo Medical Centre; 🇬🇧 Blackpool, United Kingdom

Hull Royal Infirmary; 🇬🇧 Hull, United Kingdom

Ecogene-21; 🇨🇦 Chicoutimi, Quebec, Canada

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

Evangelisches Krankenhaus Witten; 🇩🇪 Witten, Germany

Interni Ambulance; 🇨🇿 Uherské Hradiště, Czechia

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Accel Research Sites Network; 🇺🇸 Birmingham, Alabama, United States

VICIS Clinical Research; 🇺🇸 Tampa, Florida, United States

University of Michigan Hospital and Health Systems/ Dept. of Pharmacy-Research Pharmacy; 🇺🇸 Ann Arbor, Michigan, United States

Mayo Clinic; 🇺🇸 Scottsdale, Arizona, United States

Velocity Clinical Research; 🇺🇸 Cedar Park, Texas, United States

LA Universal Research Center, Inc.; 🇺🇸 Los Angeles, California, United States

America Clinical Trials; 🇺🇸 Tarzana, California, United States

Finlay Medical Research; 🇺🇸 Miami, Florida, United States

Innovia Research Center, INC; 🇺🇸 Miramar, Florida, United States

IACT Health; 🇺🇸 Columbus, Georgia, United States

Kansas University Medical Center; 🇺🇸 Kansas City, Kansas, United States

Bryan Medical Center Clinical Research; 🇺🇸 Lincoln, Nebraska, United States

West Broadway Clinic; 🇺🇸 Council Bluffs, Iowa, United States

Clinical Trials of America, LLC; 🇺🇸 Mount Airy, North Carolina, United States

Aa Mrc, Llc; 🇺🇸 Flint, Michigan, United States

Circuit Clinical (Crystal Run Healthcare); 🇺🇸 Middletown, New York, United States

Columbia University; 🇺🇸 New York, New York, United States

Circuit Clinical; 🇺🇸 Niagara Falls, New York, United States

Novant Health Cancer Institute Elizabeth Investigational Drug Services; 🇺🇸 Charlotte, North Carolina, United States

Chattanooga Research & Medicine, PLLC; 🇺🇸 Chattanooga, Tennessee, United States

Summit Research Group, LLC; 🇺🇸 Munroe Falls, Ohio, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States

Velocity Clinical; 🇺🇸 West Jordan, Utah, United States

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

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

West Virginia University Heart and Vascular Institute; 🇺🇸 Morgantown, West Virginia, United States

Royal North Shoe Hospital; 🇦🇺 Saint Leonards, New South Wales, Australia

Monash Medical Centre; 🇦🇺 Clayton S., Victoria, Australia

Medical Center Diamedical 2013 OOD; 🇧🇬 Dimitrovgrad, Bulgaria

MHAT "Dr. Tota Venkova" AD; 🇧🇬 Gabrovo, Bulgaria

Medical Center Smolyan Clinical Research OOD; 🇧🇬 Smolyan, Bulgaria

MC Doctor Kalchev OOD; 🇧🇬 Sofia, Bulgaria

EDUMED s.r.o.; 🇨🇿 Náchod, Czechia

Regionshospitalet Viborg; 🇩🇰 Viborg, Denmark

Esbjerg Hospital; 🇩🇰 Esbjerg, Denmark

Herlev Hospital; 🇩🇰 Herlev, Denmark

Bispebjerg Hospital; 🇩🇰 Frederiksberg, Denmark

Klinische Forschung Hannover-Mitte GmbH; 🇩🇪 Hannover, Germany

Hadassah Hebrew University Ein Kerm MC; 🇮🇱 Jerusalem, Israel

Azienda Ospedaliera Universitaria Federico II; 🇮🇹 Napoli, Italy

Medispektrum s.r.o., diabetologicka a metabolicka ambulancia; 🇸🇰 Bratislava, Slovakia

Cardio D&R; 🇸🇰 Košice, Slovakia

TREAD Research - Department of Cardiology; 🇿🇦 Parow, Western Cape, South Africa

Hospital Abente y Lago; 🇪🇸 A Coruña, Spain

University of Cape town - Lipid Factory; 🇿🇦 Cape Town, South Africa

Chatsmed Garden Hospital; 🇿🇦 Chatsworth, South Africa

Hospital de la Santa Creu i de Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Clinic Barcelona; 🇪🇸 Barcelona, Spain

Sahlgrenska, University Hospital; 🇸🇪 Goteborg, Västra Götalands Län, Sweden

Hospital Virgen del Rocio Edificio Centro de Diagnostico y Tratamiento (CDT); 🇪🇸 Sevilla, Spain

Karolinska University Hospital Huddinge; 🇸🇪 Stockholm, Sweden

Hospital Universitari Sant Joan de Reus.; 🇪🇸 Tarragona, Spain

Kocaeli University Faculty of Medicine; 🇹🇷 Kocaeli, Turkey

Upton Surgery; 🇬🇧 Poole, Dorset, United Kingdom

Newquay Health Centre; 🇬🇧 Newquay, Cornwall, United Kingdom

Huddersfield Royal Infirmary; 🇬🇧 Lindley, Huddersfield, United Kingdom

Mounts Bay Medical Hub; 🇬🇧 Cornwell, United Kingdom

Panthera; 🇬🇧 Preston, United Kingdom

Primary Care Sheffield; 🇬🇧 Sheffield, United Kingdom

Manchester University NHS Foundation Trust (MFT); 🇬🇧 Manchester, United Kingdom

Northwell Health; 🇺🇸 Great Neck, New York, United States

Diabetes/Lipid Management & Research Center; 🇺🇸 Huntington Beach, California, United States

Westside Center for Clinical Research; 🇺🇸 Jacksonville, Florida, United States

Medicus Alliance Clinical Research; 🇺🇸 Sugar Land, Texas, United States

Dr. Heart Pty Ltd at Cholesterol Care Australia; 🇦🇺 Woolloongabba, Queensland, Australia

Bayside Clinical Research; 🇺🇸 Trinity, Florida, United States

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia