Clinical trial NCT05610280: A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hypertriglyceridemia
Cardiovascular Diseases
Atherosclerosis
Keywords: ISIS 678354
Olezarsen
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-09
Enrollment: 1478
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This is a Phase 3, multi-center, placebo-controlled study in approximately 1475 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo
timeFrame: Baseline to Week 25
Secondary outcomes:
measure: Percent Change From Baseline to Week 53 in Fasting TG Compared to Placebo
timeFrame: Baseline to Week 53
measure: Proportion of Participants who Achieve Fasting TG <150 Milligrams per Deciliter (mg/dL) at Weeks 25 and 53 Compared to Placebo
timeFrame: Baseline, Weeks 25 and 53
measure: Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein C-III (apoC-III) Compared to Placebo
timeFrame: Baseline to Weeks 25 and 53
measure: Percent Change From Baseline to Weeks 25 and 53 in Fasting Very Low-Density Lipoprotein-Cholesterol (VLDL)-C Compared to Placebo
timeFrame: Baseline to Weeks 25 and 53
measure: Percent Change From Baseline to Weeks 25 and 53 in Fasting Remnant Cholesterol Compared to Placebo
timeFrame: Baseline to Weeks 25 and 53
measure: Percent Change From Baseline to Weeks 25 and 53 in Fasting non-High Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo
timeFrame: Baseline to Weeks 25 and 53
measure: Percent Change From Baseline to Weeks 25 and 53 in Fasting High-Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo
timeFrame: Baseline to Weeks 25 and 53
measure: Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein B (apoB) Compared to Placebo
timeFrame: Baseline to Weeks 25 and 53
measure: Percent Change From Baseline to Weeks 25 and 53 in Fasting Low-Density Lipoprotein-Cholesterol (LDL)-C Compared to Placebo
timeFrame: Baseline to Weeks 25 and 53
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics, LLC Alabaster
state: Alabama
city: Huntsville
country: United States
facility: Heart Center Research PC
state: Alabama
city: Beverly Hills
country: United States
facility: Cardiovascular Research Foundation of Southern California
state: California
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles
state: California
city: Huntington Beach
country: United States
facility: Diabetes/Lipid Management & Research Center
state: California
city: La Jolla
country: United States
facility: University of California, San Diego (UCSD)
state: California
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Northridge
country: United States
facility: Amicis Research
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Sacramento
country: United States
facility: Northern California Research
state: California
city: Santa Clarita
country: United States
facility: Amicis Research Center
state: California
city: Tarzana
country: United States
facility: Metabolic Institute of America
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
state: California
city: Valencia
country: United States
facility: Amicis Research Center
state: California
city: Boca Raton
country: United States
facility: Excel Clinical Medical Trials
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research - West Palm
state: Florida
city: Homestead
country: United States
facility: Global Research Associates
state: Florida
city: Lake Worth
country: United States
facility: 3Sync Research
state: Florida
city: Miami
country: United States
facility: Finlay Medical Research
state: Florida
city: Miami
country: United States
facility: Advanced Medical Research Institute (AMRI)
state: Florida
city: Miami
country: United States
facility: De La Cruz Research Center, LL
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc. - New Port Richey
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc. - Palm Harbor
state: Florida
city: Oakland Park
country: United States
facility: Proactive Clinical Research
state: Florida
city: Ocala
country: United States
facility: Ocala Cardiovascular Research
state: Florida
city: Plantation
country: United States
facility: Comprehensive Medical & Research Center
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Saint Augustine
country: United States
facility: St. Johns Center for Clinical Research
state: Florida
city: Tampa
country: United States
facility: JSV Clinical Research Study, Inc
state: Florida
city: Columbus
country: United States
facility: Centricity Research
state: Georgia
city: Tucker
country: United States
facility: Atlanta Heart Specialists
state: Georgia
city: Evanston
country: United States
facility: Evanston Premier Healthcare Research LLC
state: Illinois
city: Gurnee
country: United States
facility: Clinical Investigation Specialists, Inc
state: Illinois
city: Park Ridge
country: United States
facility: Affinity Health
state: Illinois
city: Munster
country: United States
facility: Cardiovascular Research of Northwest Indiana, LLC
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital and Health Care Services
state: Indiana
city: Council Bluffs
country: United States
facility: West Broadway Clinic
state: Iowa
city: West Des Moines
country: United States
facility: Mercy One Iowa Heart Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: Louisville
country: United States
facility: Norton Cardiovascular Associates
state: Kentucky
city: Louisville
country: United States
facility: Louisville Metabolic and Atherosclerosis Research Center
state: Kentucky
city: Baltimore
country: United States
facility: Maryland Cardiovascular Specialists
state: Maryland
city: Flint
country: United States
facility: Aa Mrc, Llc
state: Michigan
city: Las Vegas
country: United States
facility: Palm Research Center, Inc.
state: Nevada
city: Las Vegas
country: United States
facility: Clinical Research of South Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Palm Research Center, Inc.
state: Nevada
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: North Carolina
city: Greensboro
country: United States
facility: Moses H. Cone Memorial Hospital
state: North Carolina
city: Canton
country: United States
facility: Aultman Hospital Cardiology Clinical Trials
state: Ohio
city: Columbus
country: United States
facility: McConnell Heart Health Center
state: Ohio
city: Stow
country: United States
facility: Summit Research Group, LLC
state: Ohio
city: Edmond
country: United States
facility: Central Oklahoma Early Detection Center
state: Oklahoma
city: Lansdale
country: United States
facility: Green and Seidner Family Practice Associates
state: Pennsylvania
city: Little River
country: United States
facility: Main Street Physicians Care Waterway
state: South Carolina
city: Rock Hill
country: United States
facility: OnSite Clinical Solutions, LLC
state: South Carolina
city: Rapid City
country: United States
facility: Monument Health Clinical Research
state: South Dakota
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Jackson
country: United States
facility: The Jackson Clinic
state: Tennessee
city: Nashville
country: United States
facility: Affinity Health Corp.
state: Tennessee
city: Tullahoma
country: United States
facility: Tennessee Center for Clinical Trials
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC
state: Texas
city: McKinney
country: United States
facility: Texas Institute of Cardiology
state: Texas
city: Mesquite
country: United States
facility: Southern Endocrinology Associates
state: Texas
city: Round Rock
country: United States
facility: FMC Science
state: Texas
city: Manassas
country: United States
facility: Carient Heart & Vascular
state: Virginia
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center (CAMC) Clinical Trials Center
state: West Virginia
city: Dupnitsa
country: Bulgaria
facility: MHAT Sv. Ivan Rilski - 2003 OOD
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Pulmed OOD
city: Ruse
country: Bulgaria
facility: SHATC Medica Cor EAD
city: Sofia
country: Bulgaria
facility: Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD
city: Sofia
country: Bulgaria
facility: MBAL National Cardiology Hospital
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Alexandrovska
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment
city: Sofia
country: Bulgaria
facility: Medico Dental Center ISUL Tsaritsa Yoanna EOOD
city: Stara Zagora
country: Bulgaria
facility: UMHAT Prof. Dr. Stoyan Kirkovich
city: Varna
country: Bulgaria
facility: Diagnostic Consultative Center Equita (DCC Equita)
city: Varna
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Cardiology
city: Vancouver
country: Canada
facility: ARC Biosystems
state: British Columbia
city: Concord
country: Canada
facility: Centricity Research - Vaughan Endocrinology
state: Ontario
city: Etobicoke
country: Canada
facility: Centricity Research - Etobicoke Endocrinology
state: Ontario
city: Oshawa
country: Canada
facility: Centricity Research - Oshawa Multispecialty
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc
state: Ontario
city: Toronto
country: Canada
facility: Centricity Research - Toronto LMC Multispecialty
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute - Institut de Cardiologie de Montreal
state: Quebec
city: Montréal
country: Canada
facility: Institute de Recherches Cliniques de Montreal
state: Quebec
city: Québec
country: Canada
facility: Clinique des Maladies Lipidiques de Quebec Inc.
state: Quebec
city: Barrie
country: Canada
facility: Centricity Research - Barrie Endocrinology
city: Brampton
country: Canada
facility: Centricity Research - Brampton Endocrinology
city: Québec
country: Canada
facility: Centre de Recherche Saint-Louis
city: Brno
country: Czechia
facility: UNIVMED s.r.o. - Kardiologicka Ambulance
city: Hodonin
country: Czechia
facility: Cevni ambulance - MATMED s.r.o.
city: Jaroměř
country: Czechia
facility: Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod
city: Prague
country: Czechia
facility: Endokrinologie Cerny Most s.r.o.
city: Praha
country: Czechia
facility: Affidea Praha s.r.o.
city: Praha
country: Czechia
facility: Diabetologicka a endokrinologicka ambulance Milan Kvapil s.r.o
city: Teplice
country: Czechia
facility: AeskuLab k.s
city: Uherske Hradiste
country: Czechia
facility: MUDr. Nina Zemkova s.r.o. Interni Ambulance
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Esbjerg
country: Denmark
facility: Sydvestjysk Hospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Herning
country: Denmark
facility: Godstrup Regional Hospital (Gødstrup)
city: Svendborg
country: Denmark
facility: OUH Svendborg Hospital
city: Viborg
country: Denmark
facility: Viborg Regional Hospital
city: Bron
country: France
facility: HCL Hopital Louis Pradel
city: Dijon
country: France
facility: CHU Dijon Bourgogne - Hopital Francois Mitterrand
city: Paris
country: France
facility: AP-HP Hopital Pitie-Salpetriere
city: Valenciennes
country: France
facility: Groupement de Cooperation Sanitaire (GCS) ELSAN - Polyclinique Vauban
city: Vénissieux
country: France
facility: GHM les Portes du Sud
city: Budapest
country: Hungary
facility: Clinexpert Kft.
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum
city: Encs
country: Hungary
facility: CRU Hungary Kft.
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
city: Cinisello Balsamo
country: Italy
facility: ASST NORD MILANO-Ospedale Edoardo Bassini
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Amsterdam
country: Netherlands
facility: Academic Medical Center - Department of Vascular Medicine
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Dirksland
country: Netherlands
facility: Het Van Weel-Bethesda Ziekenhuis
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Hoogeveen
country: Netherlands
facility: Bethesda Diabetes Research Center
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis (CWZ)
city: Sneek
country: Netherlands
facility: D&A Research
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Zwijndrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis - Location Dordrecht
city: Zwijndrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Oslo
country: Norway
facility: The Lipid Clinic (Oslo University Hospital)
city: Katowice
country: Poland
facility: SALVIA Lekston i Madej s.j.
city: Krakow
country: Poland
facility: Krakowskie Centrum Medyczne Sp. z o.o.
city: Kraków
country: Poland
facility: Jagiellonskie Centrum Innowacji Sp. z o.o.
city: Poznań
country: Poland
facility: Praktyka Lekarska Ewa Krzyzagorska
city: Warsaw
country: Poland
facility: Clinical Best Solutions Sp. z.o.o Spolka Komandytowa
city: Warsaw
country: Poland
facility: Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego - Panstwowy Instytut Badawczy, Klinika Kardiologii i Angiologii Interwencyjnej
city: Warszawa
country: Poland
facility: FutureMeds Warszawa Centrum
city: Warszawa
country: Poland
facility: FutureMeds - Centrum Medyczne AMED Warszawa Targowek
city: Wrocław
country: Poland
facility: FutureMeds Sp. z o.o
city: Zabrze
country: Poland
facility: Slaski Park Technologii Medycznych Kardio-Med Silesia Sp. z o. o
city: Zamosc
country: Poland
facility: ETG Zamosc - Pro Life Medica Sp. z o.o
city: Łódź
country: Poland
facility: FutureMeds
city: Łódź
country: Poland
facility: INSTYTUT CENTRUM ZDROWIA MATKI POLKI - Klinika Kardiologii i Wad Wrodzonych Doroslych
city: Carnaxide
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
city: Bardejov
country: Slovakia
facility: Alian, s.r.o., Kardiologicka ambulancia
city: Kosice
country: Slovakia
facility: Cardio D&R, S.R.O. Kosice
city: Roznava
country: Slovakia
facility: Diab sro
city: Svidnik
country: Slovakia
facility: Interna SK, s.r.o., Kardiologicka a interna ambulancia
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Calle Villarroel 170
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: La Coruna
country: Spain
facility: Hospital Abente y Lago
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
References: