Clinical trial NCT05079919: A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 678354 Administered Subcutaneously to Patients With Severe Hypertriglyceridemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Severe Hypertriglyceridemia
Keywords: ISIS 678354
Fasting Triglycerides
Apolipoprotein C-III
Very Low-Density Lipoprotein Cholesterol
High-Density Lipoprotein-Cholesterol
Non-High-Density Lipoprotein-Cholesterol
Olezarsen
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-15
Enrollment: 617
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 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.

Eligibility criteria: Key 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

Primary outcomes:
measure: Percent Change from Baseline in Fasting TG Compared to Placebo
timeFrame: Baseline and Month 6
Secondary outcomes:
measure: Percent Change from Baseline in Fasting TG Compared to Placebo
timeFrame: Baseline and Month 12
measure: 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
timeFrame: Baseline, Month 6 and 12
measure: Proportion of Patients Who Achieve Fasting TG <500 mg/dL (5.65 mmol/L) Compared to Placebo
timeFrame: Month 12
measure: 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
timeFrame: Month 12
measure: Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo
timeFrame: Week 1 through Week 53
measure: Absolute Change in Hepatic Fat Fraction (HFF) Between Olezarsen Treatment Group and Pooled Placebo
timeFrame: Baseline through Month 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Accel Research Sites Network
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Chula Vista
country: United States
facility: Velocity Clinical Research
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: Los Angeles
country: United States
facility: LA Universal Research Center, Inc.
state: California
city: Tarzana
country: United States
facility: America Clinical Trials
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Chiefland
country: United States
facility: Southeast Clinical Research LLC
state: Florida
city: Jacksonville
country: United States
facility: Westside Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: Finlay Medical Research
state: Florida
city: Miramar
country: United States
facility: Innovia Research Center, INC
state: Florida
city: Ocala
country: United States
facility: Ocala Cardiovascular Research
state: Florida
city: Saint Petersburg
country: United States
facility: IMA Clinical Research
state: Florida
city: Tampa
country: United States
facility: VICIS Clinical Research
state: Florida
city: Trinity
country: United States
facility: Bayside Clinical Research
state: Florida
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: Chicago
country: United States
facility: IMA Clinical Research Chicago
state: Illinois
city: Oak Brook
country: United States
facility: Affinity Health
state: Illinois
city: Council Bluffs
country: United States
facility: West Broadway Clinic
state: Iowa
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Monroe
country: United States
facility: Clinical Trials of America, LLC
state: Louisiana
city: Towson
country: United States
facility: Continental Clinical Solutions
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Hospital and Health Systems/ Dept. of Pharmacy-Research Pharmacy
state: Michigan
city: Flint
country: United States
facility: Aa Mrc, Llc
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: IMA Clinical Research
state: Missouri
city: Lincoln
country: United States
facility: Bryan Medical Center Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Palm Research Center, INC.
state: Nevada
city: Union City
country: United States
facility: Hudson County Clinical Trials Research Center
state: New Jersey
city: Brooklyn
country: United States
facility: Modern Medicine
state: New York
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Middletown
country: United States
facility: Circuit Clinical (Crystal Run Healthcare)
state: New York
city: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Niagara Falls
country: United States
facility: Circuit Clinical
state: New York
city: Syosset
country: United States
facility: Modern Medical
state: New York
city: Charlotte
country: United States
facility: Novant Health Cancer Institute Elizabeth Investigational Drug Services
state: North Carolina
city: Greensboro
country: United States
facility: Cone Medical Center
state: North Carolina
city: Mount Airy
country: United States
facility: Clinical Trials of America, LLC
state: North Carolina
city: Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Aventiv Research
state: Ohio
city: Munroe Falls
country: United States
facility: Summit Research Group, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Hightower Clinical Trial Services
state: Oklahoma
city: Medford
country: United States
facility: Velocity Clinical Research
state: Oregon
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Chattanooga
country: United States
facility: Chattanooga Research & Medicine, PLLC
state: Tennessee
city: Cedar Park
country: United States
facility: Velocity Clinical Research
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Sugar Land
country: United States
facility: Medicus Alliance Clinical Research
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical
state: Utah
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Norfolk
country: United States
facility: York Clinical Research LLC
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Heart and Vascular Institute
state: West Virginia
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shoe Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Dr. Heart Pty Ltd at Cholesterol Care Australia
state: Queensland
city: Clayton S.
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Blagoevgrad
country: Bulgaria
facility: MHAT Blagoevgrad AD
city: Burgas
country: Bulgaria
facility: Medical Center Doctor Staykov EOOD
city: Dimitrovgrad
country: Bulgaria
facility: Medical Center Diamedical 2013 OOD
city: Gabrovo
country: Bulgaria
facility: MHAT "Dr. Tota Venkova" AD
city: Montana
country: Bulgaria
facility: Medical Center "Hera" EOOD
city: Plovdiv
country: Bulgaria
facility: SHAT "Special Medic" Ltd
city: Ruse
country: Bulgaria
facility: Medical Center Rusemed EOOD
city: Sliven
country: Bulgaria
facility: DCC 1 Sliven
city: Sliven
country: Bulgaria
facility: Gabriela Zhelyazkova
city: Smolyan
country: Bulgaria
facility: Medical Center Smolyan Clinical Research OOD
city: Sofia
country: Bulgaria
facility: Medical Center Endomedical EOOD
city: Sofia
country: Bulgaria
facility: Medical Centar "KALIMAT"
city: Sofia
country: Bulgaria
facility: MC Doctor Kalchev OOD
city: Sofia
country: Bulgaria
facility: UMHAT Sofiamed OOD
city: Stara Zagora
country: Bulgaria
facility: New Rehabilitation Center
city: Stara Zagora
country: Bulgaria
facility: UMHAT Prof. Dr. Stoyan Kirkovich AD, Clinic of Cardiology
city: Veliko Tarnovo
country: Bulgaria
facility: Medical Centre Nevromedics EOOD
city: Vancouver
country: Canada
facility: Arc Biosystems
state: British Columbia
city: Toronto
country: Canada
facility: Canadian Phase Onward Inc
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montréal
country: Canada
facility: Institut de recherches cliniques de Montréal (IRCM)
state: Quebec
city: Québec
country: Canada
facility: Clinique des Maladies Lipidiques de Quebec Inc.
state: Quebec
city: Brandýs Nad Labem
country: Czechia
facility: MEDICUS SERVICES s.r.o.
city: Hradec Králové
country: Czechia
facility: EDUMED s.r.o.
city: Hradec Králové
country: Czechia
facility: Fakultní nemocnice Hradec Králové
city: Náchod
country: Czechia
facility: EDUMED s.r.o.
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice
city: Prague
country: Czechia
facility: Lekarna Poliklinika Hurka
city: Uherské Hradiště
country: Czechia
facility: Interni Ambulance
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Esbjerg
country: Denmark
facility: Esbjerg Hospital
city: Frederiksberg
country: Denmark
facility: Bispebjerg Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Herning
country: Denmark
facility: Godstrup Regional Hospital
city: Viborg
country: Denmark
facility: Regionshospitalet Viborg
city: Turku
country: Finland
facility: Turku University Hospital
city: Ylitornio
country: Finland
facility: Ylitornio Health Care Center
city: Bron
country: France
facility: Hôpital Louis Pradel
city: Dijon
country: France
facility: CHU Dijon Bourgogne
city: Marseille
country: France
facility: Hopital de la Conception
city: Montpellier
country: France
facility: CHU Montpellier - Hôpital Lapeyronie
city: Paris
country: France
facility: Hopital Pitie Salpetriere APHP
city: Saint-Herblain
country: France
facility: CHU Nantes - Hopital Nord Laennec
city: Berlin
country: Germany
facility: Stoffwechselcentrum Charite Campus Virchow
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden
city: Hamburg
country: Germany
facility: Klinische Forschung Hamburg GmbH
city: Hannover
country: Germany
facility: Klinische Forschung Hannover-Mitte GmbH
city: Heidelberg
country: Germany
facility: St. Josefskrankenhaus,
city: Köln
country: Germany
facility: Uniklinik Köln
city: Markkleeberg
country: Germany
facility: Praxis Dr. med. Taggeselle
city: Papenburg
country: Germany
facility: Kardiologische Praxis in Papenburg
city: Witten
country: Germany
facility: Evangelisches Krankenhaus Witten
city: Hatvan
country: Hungary
facility: BKS Research Kft
state: Heves
city: Nyíregyháza
country: Hungary
facility: Medifarma 98 Kft
state: Szabolcs-Szatmar-Bereg
city: Borsod
country: Hungary
facility: CRU Hungary Kft
city: Budapest
country: Hungary
facility: Észak-Pesti Centrumkórház - Honvédkórház; II. Belgyógyászati Osztály
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Kardiológiai Rehabilitacio
city: Debrecen
country: Hungary
facility: Belinus BT
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Belgyogyaszat A epulet
city: Miskolc
country: Hungary
facility: IPR Hungary Kft.
city: Nyíregyháza
country: Hungary
facility: Borbanya Praxis Eü KFT
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Veszprém
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft
city: Be'er Sheva
country: Israel
facility: SOROKA Medical Center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Ein Kerm MC
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di SantOrsola
city: Milano
country: Italy
facility: Ospdale E. Bassini
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Palermo
country: Italy
facility: A.O. Policlinico Universitario P. Giaccone
city: Roma
country: Italy
facility: Policlinico Umberto
city: Roma
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: Rijnstate Arnhem
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer ziekenhuis
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Grafton
country: New Zealand
facility: Auckland City Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research
city: Newtown
country: New Zealand
facility: Wellington Regional Hospital
city: Oslo
country: Norway
facility: Lipid Clinic
city: Katowice
country: Poland
facility: Salvia
city: Poznan
country: Poland
facility: Praktyka Lekarska Ewa Krzyzagorska
city: Skierniewice
country: Poland
facility: ClinMedica Research Sp.z o.o.
city: Tarnów
country: Poland
facility: Osrodek Badan Klinicznych Metabolica
city: Wroclaw
country: Poland
facility: Futuremeds sp. z o.o
city: Łódz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki Klinika
city: Aveiro
country: Portugal
facility: Centro Hospitalar do Baixo Vouga Hospital Infante D. Pedro
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra, EPE
city: Lisbon
country: Portugal
facility: Hospital Egas Moniz - Centro Hospitalar de Lisboa Ocidental
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário de São João Consultas Externas de Endocrinologia K13
city: Vila Nova De Gaia
country: Portugal
facility: Centro Hospitalar
city: Bratislava
country: Slovakia
facility: Medispektrum s.r.o., diabetologicka a metabolicka ambulancia
city: Brezno
country: Slovakia
facility: Nemocnica s poliklinikou Brezno
city: Kosice
country: Slovakia
facility: Vychodoslovensky Ustav srdcovych a cievnych chorob a.s.
city: Košice
country: Slovakia
facility: Human-Care s.r.o.
city: Košice
country: Slovakia
facility: Cardio D&R
city: Svidnik
country: Slovakia
facility: Nemocnica arm. generala L. Svobodu Svidnik,
city: Bloemfontein
country: South Africa
facility: Iatros International
state: Free State
city: Centurion
country: South Africa
facility: Unitas Hospital
state: Gauteng
city: Cape Town
country: South Africa
facility: Dr Jan Engelbrecht and Ass. Inc
state: Western Cape
city: Parow
country: South Africa
facility: TREAD Research - Department of Cardiology
state: Western Cape
city: Cape Town
country: South Africa
facility: University of Cape town - Lipid Factory
city: Chatsworth
country: South Africa
facility: Chatsmed Garden Hospital
city: A Coruña
country: Spain
facility: Hospital Abente y Lago
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Institut d'Investigació i Innovació Parc Taulí (I3PT) Departament Medicina Universitat
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio Edificio Centro de Diagnostico y Tratamiento (CDT)
city: Tarragona
country: Spain
facility: Hospital Universitari Sant Joan de Reus.
city: Goteborg
country: Sweden
facility: Sahlgrenska, University Hospital
state: Västra Götalands Län
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: İzmir
country: Turkey
facility: Ege University School of Medicine, Department of Cardiology
city: Kocaeli
country: Turkey
facility: Kocaeli University Faculty of Medicine
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Medical Faculty
city: Liskeard
country: United Kingdom
facility: Oak Tree Surgery and Pensilva Health Centre
state: Cornwall
city: Newquay
country: United Kingdom
facility: Newquay Health Centre
state: Cornwall
city: Poole
country: United Kingdom
facility: Upton Surgery
state: Dorset
city: Rochdale
country: United Kingdom
facility: Panthera Biopartners
state: England
city: Sheffield
country: United Kingdom
facility: Panthera Biopartners
state: England
city: Lindley
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: Huddersfield
city: Corby
country: United Kingdom
facility: Lakeside Healthcare at Corby
state: Northamptonshire
city: Lyne
country: United Kingdom
facility: Sandwell General Hospital
state: West Bromwich
city: Blackpool
country: United Kingdom
facility: Waterloo Medical Centre
city: Cornwell
country: United Kingdom
facility: Mounts Bay Medical Hub
city: Glasgow
country: United Kingdom
facility: Panthera
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: London
country: United Kingdom
facility: Panthera
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust (MFT)
city: Preston
country: United Kingdom
facility: Panthera
city: Sheffield
country: United Kingdom
facility: Primary Care Sheffield
Study officials:
References: