A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia

Cardiovascular Diseases Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study of Olezarsen (ISIS 678354) in Patients With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), or With Severe Hypertriglyceridemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05610280
• Other study ID #: ISIS 678354-CS9
• Secondary ID: 2022-501486-53
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 21, 2022
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo in participants with hypertriglyceridemia and atherosclerotic cardiovascular disease, or with severe hypertriglyceridemia.

Description:

This is a Phase 3, multi-center, placebo-controlled study of up to 1312 participants with hypertriglyceridemia and atherosclerotic cardiovascular disease. The study consists of 3 periods: 1) Screening Period: Week -12 to Week -1 (up to 12 weeks); 2) Treatment Period up to Week 53; and 3) Post-Treatment Follow-up Period: Week 54 to Week 66 (13 weeks). Participants enrolled will receive olezarsen or placebo once every 4 weeks during the 53-week Treatment Period.

The Screening Period was extended with no impact to overall study timelines. Endpoints added to provide assessment on the pancreatitis rate after olezarsen reaches steady state levels.

A coronary computed tomographic angiography (CTA) sub study will be performed to assess whether triglyceride lowering through inhibition of apoC-III protein synthesis may reduce coronary plaque progression.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1478
• Est. completion date: June 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must fall into 1 of the following groups (a or b):

a. Hypertriglyceridemia with fasting TG =200 mg/dL (2.26 millimoles per liter [mmol/L]) and <500 mg/dL (5.65 mmol/L) with either

• Clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or

• At increased risk for ASCVD

b. Severe hypertriglyceridemia with fasting TG =500 mg/dL (5.65 mmol/L)

• Participants should be on standard of care (SOC) lipid-lowering medications 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.

Exclusion Criteria:

• Hemoglobin A1c (HbA1c) = 9.5% at Screening

• Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal

• Total bilirubin > 1.5 upper limit of normal unless due to Gilbert's syndrome

• Estimated GFR < 30 mL/min/1.73 m^2

NOTE: Other Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases
• Hypertriglyceridemia

Intervention

Drug:
• Olezarsen
Olezarsen will be administered by SC injection.
• Placebo
Olezarsen-matching placebo will be administered by SC injection.

Locations

Country	Name	City	State
Bulgaria	MHAT Sv. Ivan Rilski - 2003 OOD	Dupnitsa
Bulgaria	University Multiprofile Hospital for Active Treatment Pulmed OOD	Plovdiv
Bulgaria	SHATC Medica Cor EAD	Ruse
Bulgaria	MBAL National Cardiology Hospital	Sofia
Bulgaria	Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD	Sofia
Bulgaria	Medico Dental Center ISUL Tsaritsa Yoanna EOOD	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment Alexandrovska	Sofia
Bulgaria	UMHAT Prof. Dr. Stoyan Kirkovich	Stara Zagora
Bulgaria	Diagnostic Consultative Center Equita (DCC Equita)	Varna
Bulgaria	Specialized Hospital for Active Treatment of Cardiology	Varna
Canada	Centricity Research - Barrie Endocrinology	Barrie
Canada	Centricity Research - Brampton Endocrinology	Brampton
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Centricity Research - Vaughan Endocrinology	Concord	Ontario
Canada	Centricity Research - Etobicoke Endocrinology	Etobicoke	Ontario
Canada	Montreal Heart Institute - Institut de Cardiologie de Montreal	Montreal	Quebec
Canada	Institute de Recherches Cliniques de Montreal	Montréal	Quebec
Canada	Centricity Research - Oshawa Multispecialty	Oshawa	Ontario
Canada	Centre de Recherche Saint-Louis	Québec
Canada	Clinique des Maladies Lipidiques de Quebec Inc.	Québec	Quebec
Canada	Bluewater Clinical Research Group Inc	Sarnia	Ontario
Canada	Centricity Research - Toronto LMC Multispecialty	Toronto	Ontario
Canada	ARC Biosystems	Vancouver	British Columbia
Czechia	UNIVMED s.r.o. - Kardiologicka Ambulance	Brno
Czechia	Cevni ambulance - MATMED s.r.o.	Hodonin
Czechia	Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod	Jaromer
Czechia	Endokrinologie Cerny Most s.r.o.	Prague
Czechia	Affidea Praha s.r.o.	Praha
Czechia	Diabetologicka a endokrinologicka ambulance Milan Kvapil s.r.o	Praha
Czechia	AeskuLab k.s	Teplice
Czechia	MUDr. Nina Zemkova s.r.o. Interni Ambulance	Uherske Hradiste
Denmark	Aarhus University Hospital	Aarhus
Denmark	Sydvestjysk Hospital	Esbjerg
Denmark	Gentofte Hospital	Hellerup
Denmark	Godstrup Regional Hospital (Gødstrup)	Herning
Denmark	OUH Svendborg Hospital	Svendborg
Denmark	Viborg Regional Hospital	Viborg
France	HCL Hopital Louis Pradel	Bron
France	CHU Dijon Bourgogne - Hopital Francois Mitterrand	Dijon
France	AP-HP Hopital Pitie-Salpetriere	Paris
France	Groupement de Cooperation Sanitaire (GCS) ELSAN - Polyclinique Vauban	Valenciennes
France	GHM les Portes du Sud	Vénissieux
Hungary	Clinexpert Kft.	Budapest
Hungary	Obudai Egeszsegugyi Centrum	Budapest
Hungary	CRU Hungary Kft.	Encs
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola	Bologna
Italy	ASST NORD MILANO-Ospedale Edoardo Bassini	Cinisello Balsamo
Italy	Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna	Cona
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Centro Cardiologico Monzino	Milano
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore	Rome
Netherlands	Academic Medical Center - Department of Vascular Medicine	Amsterdam
Netherlands	Ziekenhuis Rijnstate	Arnhem
Netherlands	Reinier de Graaf Gasthuis	Delft
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Het Van Weel-Bethesda Ziekenhuis	Dirksland
Netherlands	Groene Hart Ziekenhuis	Gouda
Netherlands	Spaarne Gasthuis	Haarlem
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Bethesda Diabetes Research Center	Hoogeveen
Netherlands	Canisius-Wilhelmina Ziekenhuis (CWZ)	Nijmegen
Netherlands	D&A Research	Sneek
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Netherlands	Maxima Medisch Centrum	Veldhoven
Netherlands	Albert Schweitzer Ziekenhuis	Zwijndrecht
Netherlands	Albert Schweitzer Ziekenhuis - Location Dordrecht	Zwijndrecht
Norway	The Lipid Clinic (Oslo University Hospital)	Oslo
Poland	SALVIA Lekston i Madej s.j.	Katowice
Poland	Krakowskie Centrum Medyczne Sp. z o.o.	Krakow
Poland	Jagiellonskie Centrum Innowacji Sp. z o.o.	Kraków
Poland	FutureMeds	Lódz
Poland	INSTYTUT CENTRUM ZDROWIA MATKI POLKI - Klinika Kardiologii i Wad Wrodzonych Doroslych	Lódz
Poland	Praktyka Lekarska Ewa Krzyzagorska	Poznan
Poland	Clinical Best Solutions Sp. z.o.o Spolka Komandytowa	Warsaw
Poland	Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego - Panstwowy Instytut Badawczy, Klinika Kardiologii i Angiologii Interwencyjnej	Warsaw
Poland	FutureMeds - Centrum Medyczne AMED Warszawa Targowek	Warszawa
Poland	FutureMeds Warszawa Centrum	Warszawa
Poland	FutureMeds Sp. z o.o	Wroclaw
Poland	Slaski Park Technologii Medycznych Kardio-Med Silesia Sp. z o. o	Zabrze
Poland	ETG Zamosc - Pro Life Medica Sp. z o.o	Zamosc
Portugal	Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz	Carnaxide
Portugal	Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz	Lisboa
Portugal	Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria	Lisboa
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho EPE	Vila Nova de Gaia
Slovakia	Alian, s.r.o., Kardiologicka ambulancia	Bardejov
Slovakia	Cardio D&R, S.R.O. Kosice	Kosice
Slovakia	Diab sro	Roznava
Slovakia	Interna SK, s.r.o., Kardiologicka a interna ambulancia	Svidnik
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Calle Villarroel 170	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	El Palmar
Spain	Hospital Abente y Lago	La Coruna
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
United States	Maryland Cardiovascular Specialists	Baltimore	Maryland
United States	Cardiovascular Research Foundation of Southern California	Beverly Hills	California
United States	Westside Medical Associates of Los Angeles	Beverly Hills	California
United States	Alabama Clinical Therapeutics, LLC Alabaster	Birmingham	Alabama
United States	Excel Clinical Medical Trials	Boca Raton	Florida
United States	Aultman Hospital Cardiology Clinical Trials	Canton	Ohio
United States	Charleston Area Medical Center (CAMC) Clinical Trials Center	Charleston	West Virginia
United States	Medical University of South Carolina (MUSC)	Charleston	North Carolina
United States	Centricity Research	Columbus	Georgia
United States	McConnell Heart Health Center	Columbus	Ohio
United States	West Broadway Clinic	Council Bluffs	Iowa
United States	Central Oklahoma Early Detection Center	Edmond	Oklahoma
United States	Evanston Premier Healthcare Research LLC	Evanston	Illinois
United States	Aa Mrc, Llc	Flint	Michigan
United States	Finlay Medical Research - West Palm	Greenacres City	Florida
United States	Moses H. Cone Memorial Hospital	Greensboro	North Carolina
United States	Clinical Investigation Specialists, Inc	Gurnee	Illinois
United States	Global Research Associates	Homestead	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Juno Research, LLC	Houston	Texas
United States	Diabetes/Lipid Management & Research Center	Huntington Beach	California
United States	Heart Center Research PC	Huntsville	Alabama
United States	The Jackson Clinic	Jackson	Tennessee
United States	University of Kansas Medical Center (KUMC)	Kansas City	Kansas
United States	University of California, San Diego (UCSD)	La Jolla	California
United States	3Sync Research	Lake Worth	Florida
United States	Green and Seidner Family Practice Associates	Lansdale	Pennsylvania
United States	Clinical Research of South Nevada	Las Vegas	Nevada
United States	Palm Research Center, Inc.	Las Vegas	Nevada
United States	Palm Research Center, Inc.	Las Vegas	Nevada
United States	Clinical Trials Research	Lincoln	California
United States	Main Street Physicians Care Waterway	Little River	South Carolina
United States	Louisville Metabolic and Atherosclerosis Research Center	Louisville	Kentucky
United States	Norton Cardiovascular Associates	Louisville	Kentucky
United States	Carient Heart & Vascular	Manassas	Virginia
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Texas Institute of Cardiology	McKinney	Texas
United States	Southern Endocrinology Associates	Mesquite	Texas
United States	Advanced Medical Research Institute (AMRI)	Miami	Florida
United States	De La Cruz Research Center, LL	Miami	Florida
United States	Finlay Medical Research	Miami	Florida
United States	Cardiovascular Research of Northwest Indiana, LLC	Munster	Indiana
United States	Affinity Health Corp.	Nashville	Tennessee
United States	Suncoast Clinical Research, Inc. - New Port Richey	New Port Richey	Florida
United States	Suncoast Clinical Research, Inc. - Palm Harbor	New Port Richey	Florida
United States	Amicis Research	Northridge	California
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Proactive Clinical Research	Oakland Park	Florida
United States	Ocala Cardiovascular Research	Ocala	Florida
United States	Affinity Health	Park Ridge	Illinois
United States	Comprehensive Medical & Research Center	Plantation	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Health Concepts	Rapid City	South Dakota
United States	Monument Health Clinical Research	Rapid City	South Dakota
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	OnSite Clinical Solutions, LLC	Rock Hill	South Carolina
United States	FMC Science	Round Rock	Texas
United States	Northern California Research	Sacramento	California
United States	St. Johns Center for Clinical Research	Saint Augustine	Florida
United States	Amicis Research Center	Santa Clarita	California
United States	Summit Research Group, LLC	Stow	Ohio
United States	JSV Clinical Research Study, Inc	Tampa	Florida
United States	Metabolic Institute of America	Tarzana	California
United States	Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center	Torrance	California
United States	Atlanta Heart Specialists	Tucker	Georgia
United States	Tennessee Center for Clinical Trials	Tullahoma	Tennessee
United States	Amicis Research Center	Valencia	California
United States	Mercy One Iowa Heart Center	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Hungary,  Italy,  Netherlands,  Norway,  Poland,  Portugal,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo		Baseline to Week 25
Secondary	Percent Change From Baseline to Week 53 in Fasting TG Compared to Placebo		Baseline to Week 53
Secondary	Proportion of Participants who Achieve Fasting TG <150 Milligrams per Deciliter (mg/dL) at Weeks 25 and 53 Compared to Placebo		Baseline, Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein C-III (apoC-III) Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting Very Low-Density Lipoprotein-Cholesterol (VLDL)-C Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting Remnant Cholesterol Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting non-High Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting High-Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting Total Cholesterol (TC) Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein B (apoB) Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein B-48 (apoB-48) Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting Low-Density Lipoprotein-Cholesterol (LDL)-C Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein A-1 (apoA-1) Compared to Placebo		Baseline to Weeks 25 and 53
Secondary	Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo in Participants With = 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment		Week 1 through Week 53
Secondary	Adjudicated Acute Pancreatitis Event Rate from Week 13 to Week 53 Compared to Placebo in Participants With = 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment		Week 13 through Week 53
Secondary	Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo		Week 1 through Week 53
Secondary	Adjudicated Acute Pancreatitis Event Rate from Week 13 to Week 53 Compared to Placebo		Week 13 through Week 53