A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia

Phase 3

Active, not recruiting

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

• Registration Number: NCT05552326
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

The purpose of this 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 Phase 3, multi-center, randomized, double-blind, placebo-controlled study in 446 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 Start: 2022-08-31
• Study First Submitted: 2022-09-20
• Study First Submitted QC: 2022-09-20
• Study First Posted: 2022-09-23
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29
• Primary Completion: 2025-06
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 446

Inclusion Criteria

1. Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification
2. Participants 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.
3. Participants must be willing to comply with diet and lifestyle recommendations as able.

Exclusion Criteria

1. Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
2. Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
3. Total bilirubin > 1.5 ULN unless due to Gilbert's syndrome
4. Estimated GFR < 30 mL/min/1.73 m^2

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Olezarsen-matching placebo will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.
Olezarsen	Olezarsen	Olezarsen will be administered once every 4 weeks by subcutaneous (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 Patients Who Achieve Fasting TG <500 mg/dL (5.65 mmol/L) Compared to Placebo	Month 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
Absolute Change in Hepatic Fat Fraction (HFF) Between Olezarsen Treatment Group and Pooled Placebo	Baseline through Month 12

Trial Locations

Locations (202)

Clinical Investigation Specialists Inc.; 🇺🇸 Kenosha, Wisconsin, United States

NRC Research Institute; 🇺🇸 Los Angeles, California, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Maryland School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Columbus Clinical Services; 🇺🇸 Miami, Florida, United States

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

Maryland Cardiovascular Specialists; 🇺🇸 Baltimore, Maryland, United States

Virga Jessa Hospital; 🇧🇪 Hasselt, Belgium

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

NL Health Services; 🇨🇦 Saint John's, Newfoundland and Labrador, Canada

Hospital CUF Tejo; 🇵🇹 Lisboa, Portugal

Centro de Investigación Cardiométabolica de Aguascalientes S.A. de C.V.; 🇲🇽 Aguascalientes, Mexico

Ambulancia diabetologicka a poruch latkovej premeny a vyzivy; 🇸🇰 Bratislava, Slovakia

Taichung Veterans General Hospital; 🇨🇳 Taichung City, Taiwan

Medical Center Diamedical EOOD; 🇧🇬 Dimitrovgrad, Bulgaria

MHAT Sliven to MMA Sofia; 🇧🇬 Sliven, Bulgaria

Eternal Hospital; 🇮🇳 Jaipur, India

University of Florida Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Northeast Georgia Medical Center; 🇺🇸 Gainesville, Georgia, United States

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

Accel Research Sites; 🇺🇸 DeLand, Florida, United States

OnSite Clinical Solutions, LLC; 🇺🇸 Salisbury, North Carolina, United States

Stern Cardiovascular; 🇺🇸 Southaven, Mississippi, United States

University of Kansas Medical Center (KUMC); 🇺🇸 Kansas City, Kansas, United States

Grace Research, LLC; 🇺🇸 Bossier City, Louisiana, United States

Accel Clinical Research; 🇺🇸 Eatonton, Georgia, United States

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

The Research Group of Lexington, LLC; 🇺🇸 Lexington, Kentucky, United States

Glenny Corp SA; 🇦🇷 Buenos Aires, Argentina

Randomize Now; 🇺🇸 Newnan, Georgia, United States

St. Vincent Medical Group; 🇺🇸 Carmel, Indiana, United States

Clinical Trials of America LA, LLC; 🇺🇸 Monroe, Louisiana, United States

Vilo Research Group; 🇺🇸 Houston, Texas, United States

Diabetes and Endocrinology Consultants, P.C.; 🇺🇸 Morehead City, North Carolina, United States

Tranquil Research; 🇺🇸 Webster, Texas, United States

Sante Clinical Research, LLC; 🇺🇸 Kerrville, Texas, United States

University General Hospital of Alexandroupoli; 🇬🇷 Alexandroupoli, Greece

MHAT Pazardzhik AD; 🇧🇬 Pazardzhik, Bulgaria

Fundacion Favaloro; 🇦🇷 Ciudad Autónoma de Buenos Aires, Argentina

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

Monument Health Clinical Research; 🇺🇸 Rapid City, South Dakota, United States

Instituto do Coração - HCFMUSP; 🇧🇷 São Paulo, Brazil

Oklahoma Heart Institute; 🇺🇸 Tulsa, Oklahoma, United States

Pioneer Research Solutions, Inc; 🇺🇸 Houston, Texas, United States

Texas Institute of Cardiology; 🇺🇸 McKinney, Texas, United States

Centro Medico San Luis; 🇦🇷 San Luis, Argentina

Hospital Universitario Walter Cantidio - UFC; 🇧🇷 Fortaleza, Brazil

DCT - McAllen Primary Care, LLC; 🇺🇸 McAllen, Texas, United States

SV Research LLC; 🇺🇸 Marion, Ohio, United States

Ogden Clinic Grandview; 🇺🇸 Roy, Utah, United States

NUPEC - Nucleo de Pesquisa Clinica; 🇧🇷 Belo Horizonte, Brazil

AHEPA University General Hospital of Thessaloniki; 🇬🇷 Thessaloníki, Greece

Juno Research; 🇺🇸 Houston, Texas, United States

GHM les Portes du Sud; 🇫🇷 Vénissieux, France

Texas Health Family Care; 🇺🇸 Fort Worth, Texas, United States

UMHAT - Kaspela EOOD; 🇧🇬 Plovdiv, Bulgaria

UMHAT Kanev AD; 🇧🇬 Ruse, Bulgaria

The Jackson Clinic; 🇺🇸 Jackson, Tennessee, United States

Aspen Clinical Research; 🇺🇸 Orem, Utah, United States

AZ Sint-Jan Brugge; 🇧🇪 Brugge, Belgium

Hôpital Erasme; 🇧🇪 Brussels, Belgium

CIPREC - Centro de Investigación y Prevención Cardiovascular; 🇦🇷 Ciudad Autónoma de Buenos Aires, Argentina

Sir Ganga Ram Hospital; 🇮🇳 Delhi, India

Klinikiniai sprendimai; 🇱🇹 Kaunas, Lithuania

Clinic of Cardiology and Rehabilitation; 🇱🇹 Klaipėda, Lithuania

University Malaya Medical Centre (UMMC); 🇲🇾 Kuala Lumpur, Malaysia

Clinstile, S.A. de C.V.; 🇲🇽 Mexico City, Mexico

Centro Hospitalar de Entre Douro e Vouga; 🇵🇹 Santa Maria Da Feira, Portugal

Clinical Best Solutions; 🇵🇱 Lublin, Poland

Etg Lublin; 🇵🇱 Lublin, Poland

AHEPA Building of Evaggelismos; 🇬🇷 Athens, Greece

Albert Schweitzer Ziekenhuis; 🇳🇱 Dordrecht, Netherlands

Bethesda Diabetes Research Center; 🇳🇱 Hoogeveen, Netherlands

CPQuali Pesquisa Clinica; 🇧🇷 São Paulo, Brazil

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP; 🇧🇷 Sao Paulo, Brazil

MHAT Haskovo AD; 🇧🇬 Haskovo, Bulgaria

i9 Pesquisas Clínicas/Loema - Instituto de Pesquisas Clínica & Consultores; 🇧🇷 São Paulo, Brazil

Clinexpert Kft.; 🇭🇺 Budapest, Hungary

KEM Hospital; 🇮🇳 Mumbai, India

Pirmoji viltis; 🇱🇹 Šiauliai, Lithuania

Cabinet Medical Individual SC DIANA BARBONTA SRL; 🇷🇴 Alba, Romania

S.C. Mediab Srl; 🇷🇴 Târgu-Mureş, Romania

Alian s.r.o.; 🇸🇰 Bardejov, Slovakia

Centrum Medyczne Pratia; 🇵🇱 Katowice, Poland

Narodowy Instytut Kardiologii im. S. Wyszyńskiego - PIB; 🇵🇱 Warszawa, Poland

Hygeia Hospital; 🇬🇷 Athens, Greece

DRC Gyogyszervizsgalo Kozpont Kft; 🇭🇺 Balatonfured, Hungary

Obudai Egeszsegugyi Centrum; 🇭🇺 Budapest, Hungary

Unite de Recherche Clinique; 🇨🇦 St Jerome, Quebec, Canada

Fondazione I.R.C.C.S. Policlinico "San Matteo" c/o C.U.R.M.; 🇮🇹 Pavia, Italy

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Manipal Hospital Mysore; 🇮🇳 Mysore, India

Pulau Pinang Hospital; 🇲🇾 George Town, Pulau Pinang, Malaysia

Medical Care and Research S.A de C.V.; 🇲🇽 Mérida, Yucatan, Mexico

Cientia Investigacion Clinica Sc; 🇲🇽 Chihuahua, Mexico

Clinical Best Solutions Sp. Z.o.o Spolka Komandytowa; 🇵🇱 Warsaw, Poland

University General Hospital ATTIKON; 🇬🇷 Athens, Greece

Gelre Ziekenhuizen Apeldoorn; 🇳🇱 Apeldoorn, Netherlands

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII; 🇮🇹 Bergamo, Italy

Medical Center Zara - Med; 🇧🇬 Stara Zagora, Bulgaria

Lausmed Kft.; 🇭🇺 Baja, Hungary

Pharma4 Trial Kft.; 🇭🇺 Gyöngyös, Hungary

B. M. Birla Heart Research Centre A Unit of the Calcutta Medical Research Institute; 🇮🇳 Kolkata, West Bengal, India

Sultanah Bahiyah Hospital; 🇲🇾 Alor Setar, Kedah, Malaysia

Sri Jayadeva Institute of Cardiovascular Sciences and Research; 🇮🇳 Bengaluru, India

IPGMER; 🇮🇳 Kolkata, India

Vinaya Hospital and Research Centre (A Unit of Karnataka Institute of Medical Sciences); 🇮🇳 Mangaluru, India

Cardioplus Center SRL; 🇷🇴 Baia Mare, Romania

Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed S.R.L; 🇷🇴 Braşov, Romania

UCK, I Klinika Kardiologii; 🇵🇱 Gdańsk, Poland

Centrum Zdrowia Metabolicznego; 🇵🇱 Poznan, Poland

Het Van Weel Bethesda ziekenhuis; 🇳🇱 Dirksland, Netherlands

Hospital Comarcal Infanta Elena; 🇪🇸 Huelva, Spain

AORN S. Anna e S. Sebastiano UOC FARMACIA; 🇮🇹 Caserta, Italy

Bhatia Hospital; 🇮🇳 Mumbai, India

Saules seimons medicinos centras; 🇱🇹 Kaunas, Lithuania

Republican Panevezys Hospital; 🇱🇹 Panevėžys, Lithuania

Centrul Medical Medicover Victoria; 🇷🇴 Bucuresti, Romania

Cardio Med SRL; 🇷🇴 Târgu-Mureş, Romania

Interna SK, s.r.o.; 🇸🇰 Svidník, Slovakia

Hospital Universitario Virgen Macarena; 🇪🇸 Sevilla, Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH); 🇨🇳 Kaohsiung, Taiwan

ETG Zamosc / Pro Life Medica Sp. z o.o.; 🇵🇱 Zamość, Poland

Vumc Amsterdam Medical Center; 🇳🇱 Amsterdam, Netherlands

Reinier de Graaf Ziekenhuis; 🇳🇱 Delft, Netherlands

Canisius-Wilhelmina Ziekenhuis (CWZ); 🇳🇱 Nijmegen, Netherlands

Hospital Universitario de Jaen; 🇪🇸 Jaén, Spain

Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna; 🇮🇹 Cona, Italy

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Hospital Taiping; 🇲🇾 Taiping, Perak, Malaysia

S.C. SAL MED S.R.L., Cardiologie; 🇷🇴 Piteşti, Romania

Chang Gung Medical Foundation - Linkou Branch; 🇨🇳 Taoyuan, Taiwan

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Interna a diabetologicka ambulancia - IN-DIA s.r.o.; 🇸🇰 Lučenec, Slovakia

Diab sro; 🇸🇰 Rožňava, Slovakia

Areteus s.r.o; 🇸🇰 Trebišov, Slovakia

Mackay Memorial Hospital; 🇨🇳 New Taipei City, Taiwan

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Acardo MedSite; 🇸🇪 Solna, Sweden

Hospital Provincial de Conxo; 🇪🇸 Santiago De Compostela, Spain

Diabetes & Glandular Disease Clinic, P.A.; 🇺🇸 San Antonio, Texas, United States

Núcleo de Pesquisa Clínica; 🇧🇷 Curitiba, Brazil

Nucleo de Pesquisa em Cirurgia Vascular; 🇧🇷 Porto Alegre, Brazil

IBPClin Pesquisa Clinica; 🇧🇷 Rio De Janeiro, Brazil

Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

Alabama Clinical Therapeutics, LLC Alabaster; 🇺🇸 Birmingham, Alabama, United States

Unidad de Ensayos Clinicos; 🇪🇸 Malaga, Spain

Somogy Varmegyei Kaposi Mor Oktato Korhaz Diabetologiai szakrendeles; 🇭🇺 Kaposvár, Hungary

NYU Langone Hospital - Long Island; 🇺🇸 Mineola, New York, United States

Instituto Médico DAMIC; 🇦🇷 Córdoba, Argentina

Clínica FUSAVIM Privada; 🇦🇷 Villa María, Argentina

Meridien Research; 🇺🇸 Maitland, Florida, United States

3Sync Research; 🇺🇸 Sunrise, Florida, United States

Metabolic Research Institute; 🇺🇸 West Palm Beach, Florida, United States

FMC Science; 🇺🇸 Lampasas, Texas, United States

Southern Endocrinology Associates; 🇺🇸 Mesquite, Texas, United States

SMS Clinical Research, LLC; 🇺🇸 Mesquite, Texas, United States

The Ohio State University (OSU); 🇺🇸 Columbus, Ohio, United States

Central Research Associates, Inc.; 🇺🇸 Birmingham, Alabama, United States

Onyx Clinical Research; 🇺🇸 Rochester Hills, Michigan, United States

Finlay Medical Research; 🇺🇸 Greenacres City, Florida, United States

Orchard Park Family Practice; 🇺🇸 Orchard Park, New York, United States

Medico Dental Center ISUL Tsaritsa Yoanna EOOD; 🇧🇬 Sofia, Bulgaria

Main Street Physicians Care Waterway; 🇺🇸 Little River, South Carolina, United States

Permian Research Foundation; 🇺🇸 Odessa, Texas, United States

Centro Médico Dra. Laura Maffei; 🇦🇷 Buenos Aires, Argentina

Instituto de Cardiología Corrientes; 🇦🇷 Corrientes, Argentina

University Multiprofile Hospital for Active Treatment Pulmed OOD; 🇧🇬 Plovdiv, Bulgaria

Acibadem City Clinic Tokuda University Hospital; 🇧🇬 Sofia, Bulgaria

Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD; 🇧🇬 Sofia, Bulgaria

Medical Centre Synexus Sofia EOOD; 🇧🇬 Sofia, Bulgaria

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

DCC Equita; 🇧🇬 Varna, Bulgaria

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

Aggarwal and Associates Ltd.; 🇨🇦 Brampton, Ontario, Canada

Joanne F. Liutkus Medicine Professional Corporation; 🇨🇦 Cambridge, Ontario, Canada

Specialized Hospital for Active Treatment of Cardiology; 🇧🇬 Varna, Bulgaria

Medical Centre "Nevromedics" EOOD; 🇧🇬 Veliko Tarnovo, Bulgaria

CTC Hodonin s.r.o.; 🇨🇿 Hodonín, Czechia

KardioBusak s.r.o.; 🇨🇿 Louny, Czechia

Endokrinologie Cerny Most s.r.o.; 🇨🇿 Praha, Czechia

AeskuLab k.s; 🇨🇿 Teplice, Czechia

Fakultni nemocnice v Motole; 🇨🇿 Prague, Czechia

Hopital de Hautepierre; 🇫🇷 Strasbourg, France

ELSAN - Polyclinique Vauban; 🇫🇷 Valenciennes, France

Diabetologická a endokrinologická ambulance Milan Kvapil; 🇨🇿 Příbram, Czechia

Clinical Research Institute S.C.; 🇲🇽 Tlanepantla, Mexico

Biokinetica; 🇵🇱 Józefów, Poland

Centrum Medycnze AMED; 🇵🇱 Warsaw, Poland

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Regional de Malaga; 🇪🇸 Malaga, Spain

Shin Kong Wu Ho-Su Memorial Hospital; 🇨🇳 Taipei City, Taiwan

Centra Medyczne Medyceusz; 🇵🇱 Łódź, Poland

UZ Leuven; 🇧🇪 Leuven, Belgium

Combined Research Orlando Phase I-IV; 🇺🇸 Orlando, Florida, United States

R & B Medical Center LLC; 🇺🇸 Tampa, Florida, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Louisville Metabolic and Atherosclerosis Research Center (L-MARC); 🇺🇸 Louisville, Kentucky, United States

Medical University of South Carolina (MUSC); 🇺🇸 Charleston, South Carolina, United States

JSV Clinical Research Study, Inc.; 🇺🇸 Tampa, Florida, United States

Max Super Specialty Hospital; 🇮🇳 New Delhi, Delhi, India