Clinical trial NCT05552326: A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Patients With Severe Hypertriglyceridemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Severe Hypertriglyceridemia
Keywords: Hypertriglyceridemia
Hyperlipidemias
Metabolic Diseases
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-09-23
Enrollment: 446
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 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.

Eligibility criteria: 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

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: Central Research Associates, Inc.
state: Alabama
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics, LLC Alabaster
state: Alabama
city: Peoria
country: United States
facility: Onyx Clinical Research
state: Arizona
city: Los Angeles
country: United States
facility: NRC Research Institute
state: California
city: DeLand
country: United States
facility: Accel Research Sites
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Jacksonville
state: Florida
city: Maitland
country: United States
facility: Meridien Research
state: Florida
city: Miami
country: United States
facility: Columbus Clinical Services
state: Florida
city: North Miami Beach
country: United States
facility: Harmony Clinical Research, Inc
state: Florida
city: Orlando
country: United States
facility: Combined Research Orlando Phase I-IV
state: Florida
city: Sunrise
country: United States
facility: 3Sync Research
state: Florida
city: Tampa
country: United States
facility: R & B Medical Center LLC
state: Florida
city: Tampa
country: United States
facility: JSV Clinical Research Study, Inc.
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Eatonton
country: United States
facility: Accel Clinical Research
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Newnan
country: United States
facility: Randomize Now
state: Georgia
city: Carmel
country: United States
facility: St. Vincent Medical Group
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: Lexington
country: United States
facility: The Research Group of Lexington, LLC
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Louisville
country: United States
facility: Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
state: Kentucky
city: Bossier City
country: United States
facility: Grace Research, LLC
state: Louisiana
city: Monroe
country: United States
facility: Clinical Trials of America LA, LLC
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: Maryland Cardiovascular Specialists
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Flint
country: United States
facility: Onyx Clinical Research
state: Michigan
city: Rochester Hills
country: United States
facility: Onyx Clinical Research
state: Michigan
city: Southaven
country: United States
facility: Stern Cardiovascular
state: Mississippi
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: Orchard Park
country: United States
facility: Orchard Park Family Practice
state: New York
city: Lenoir
country: United States
facility: Clinical Trials of America, LLC
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes and Endocrinology Consultants, P.C.
state: North Carolina
city: Salisbury
country: United States
facility: OnSite Clinical Solutions, LLC
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University (OSU)
state: Ohio
city: Marion
country: United States
facility: SV Research LLC
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Little River
country: United States
facility: Main Street Physicians Care Waterway
state: South Carolina
city: Rapid City
country: United States
facility: Monument Health Clinical Research
state: South Dakota
city: Jackson
country: United States
facility: The Jackson Clinic
state: Tennessee
city: Fort Worth
country: United States
facility: Texas Health Family Care
state: Texas
city: Houston
country: United States
facility: Vilo Research Group
state: Texas
city: Houston
country: United States
facility: Juno Research
state: Texas
city: Houston
country: United States
facility: Juno Research
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc
state: Texas
city: Kerrville
country: United States
facility: Sante Clinical Research, LLC
state: Texas
city: Lampasas
country: United States
facility: FMC Science
state: Texas
city: McAllen
country: United States
facility: DCT - McAllen Primary Care, LLC
state: Texas
city: McKinney
country: United States
facility: Texas Institute of Cardiology
state: Texas
city: Mesquite
country: United States
facility: SMS Clinical Research, LLC
state: Texas
city: Mesquite
country: United States
facility: Southern Endocrinology Associates
state: Texas
city: Odessa
country: United States
facility: Permian Research Foundation
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic, P.A.
state: Texas
city: Webster
country: United States
facility: Tranquil Research
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
city: Roy
country: United States
facility: Ogden Clinic Grandview
state: Utah
city: Kenosha
country: United States
facility: Clinical Investigation Specialists Inc.
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Centro Médico Dra. Laura Maffei
city: Buenos Aires
country: Argentina
facility: Glenny Corp SA
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: CIPREC - Centro de Investigación y Prevención Cardiovascular
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Fundacion Favaloro
city: Corrientes
country: Argentina
facility: Instituto de Cardiología Corrientes
city: Córdoba
country: Argentina
facility: Instituto Médico DAMIC
city: San Luis
country: Argentina
facility: Centro Medico San Luis
city: Villa María
country: Argentina
facility: Clínica FUSAVIM Privada
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Brussels
country: Belgium
facility: Hôpital Erasme
city: Hasselt
country: Belgium
facility: Virga Jessa Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Belo Horizonte
country: Brazil
facility: NUPEC - Nucleo de Pesquisa Clinica
city: Curitiba
country: Brazil
facility: Núcleo de Pesquisa Clínica
city: Fortaleza
country: Brazil
facility: Hospital Universitario Walter Cantidio - UFC
city: Porto Alegre
country: Brazil
facility: Nucleo de Pesquisa em Cirurgia Vascular
city: Rio De Janeiro
country: Brazil
facility: IBPClin Pesquisa Clinica
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clinica
city: São Paulo
country: Brazil
facility: Instituto do Coração - HCFMUSP
city: São Paulo
country: Brazil
facility: i9 Pesquisas Clínicas/Loema - Instituto de Pesquisas Clínica & Consultores
city: Dimitrovgrad
country: Bulgaria
facility: Medical Center Diamedical EOOD
city: Haskovo
country: Bulgaria
facility: MHAT Haskovo AD
city: Pazardzhik
country: Bulgaria
facility: MHAT Pazardzhik AD
city: Plovdiv
country: Bulgaria
facility: UMHAT - Kaspela EOOD
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Pulmed OOD
city: Ruse
country: Bulgaria
facility: UMHAT Kanev AD
city: Sliven
country: Bulgaria
facility: MHAT Sliven to MMA Sofia
city: Smolyan
country: Bulgaria
facility: Medical Center Smolyan Clinical Research OOD
city: Sofia
country: Bulgaria
facility: Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda University Hospital
city: Sofia
country: Bulgaria
facility: Medico Dental Center ISUL Tsaritsa Yoanna EOOD
city: Sofia
country: Bulgaria
facility: Medical Centre Synexus Sofia EOOD
city: Stara Zagora
country: Bulgaria
facility: Medical Center Zara - Med
city: Varna
country: Bulgaria
facility: DCC Equita
city: Varna
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Cardiology
city: Veliko Tarnovo
country: Bulgaria
facility: Medical Centre "Nevromedics" EOOD
city: Saint John's
country: Canada
facility: NL Health Services
state: Newfoundland and Labrador
city: Brampton
country: Canada
facility: Aggarwal and Associates Ltd.
state: Ontario
city: Cambridge
country: Canada
facility: Joanne F. Liutkus Medicine Professional Corporation
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: St Jerome
country: Canada
facility: Unite de Recherche Clinique
state: Quebec
city: Hodonín
country: Czechia
facility: CTC Hodonin s.r.o.
city: Louny
country: Czechia
facility: KardioBusak s.r.o.
city: Prague
country: Czechia
facility: Fakultni nemocnice v Motole
city: Praha
country: Czechia
facility: Endokrinologie Cerny Most s.r.o.
city: Příbram
country: Czechia
facility: Diabetologická a endokrinologická ambulance Milan Kvapil
city: Teplice
country: Czechia
facility: AeskuLab k.s
city: Strasbourg
country: France
facility: Hopital de Hautepierre
city: Valenciennes
country: France
facility: ELSAN - Polyclinique Vauban
city: Vénissieux
country: France
facility: GHM les Portes du Sud
city: Alexandroupoli
country: Greece
facility: University General Hospital of Alexandroupoli
city: Athens
country: Greece
facility: AHEPA Building of Evaggelismos
city: Athens
country: Greece
facility: University General Hospital ATTIKON
city: Athens
country: Greece
facility: Hygeia Hospital
city: Thessaloníki
country: Greece
facility: AHEPA University General Hospital of Thessaloniki
city: Baja
country: Hungary
facility: Lausmed Kft.
city: Balatonfured
country: Hungary
facility: DRC Gyogyszervizsgalo Kozpont Kft
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum
city: Budapest
country: Hungary
facility: Clinexpert Kft.
city: Gyöngyös
country: Hungary
facility: Pharma4 Trial Kft.
city: Kaposvár
country: Hungary
facility: Somogy Varmegyei Kaposi Mor Oktato Korhaz Diabetologiai szakrendeles
city: New Delhi
country: India
facility: Max Super Specialty Hospital
state: Delhi
city: Kolkata
country: India
facility: B. M. Birla Heart Research Centre A Unit of the Calcutta Medical Research Institute
state: West Bengal
city: Bengaluru
country: India
facility: Sri Jayadeva Institute of Cardiovascular Sciences and Research
city: Delhi
country: India
facility: Sir Ganga Ram Hospital
city: Jaipur
country: India
facility: Eternal Hospital
city: Kolkata
country: India
facility: IPGMER
city: Mangaluru
country: India
facility: Vinaya Hospital and Research Centre (A Unit of Karnataka Institute of Medical Sciences)
city: Mumbai
country: India
facility: KEM Hospital
city: Mumbai
country: India
facility: Bhatia Hospital
city: Mysore
country: India
facility: Manipal Hospital Mysore
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Caserta
country: Italy
facility: AORN S. Anna e S. Sebastiano UOC FARMACIA
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna
city: Pavia
country: Italy
facility: Fondazione I.R.C.C.S. Policlinico "San Matteo" c/o C.U.R.M.
city: Kaunas
country: Lithuania
facility: Saules seimons medicinos centras
city: Kaunas
country: Lithuania
facility: Klinikiniai sprendimai
city: Klaipėda
country: Lithuania
facility: Clinic of Cardiology and Rehabilitation
city: Panevėžys
country: Lithuania
facility: Republican Panevezys Hospital
city: Šiauliai
country: Lithuania
facility: Pirmoji viltis
city: Alor Setar
country: Malaysia
facility: Sultanah Bahiyah Hospital
state: Kedah
city: Taiping
country: Malaysia
facility: Hospital Taiping
state: Perak
city: George Town
country: Malaysia
facility: Pulau Pinang Hospital
state: Pulau Pinang
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre (UMMC)
city: Mérida
country: Mexico
facility: Medical Care and Research S.A de C.V.
state: Yucatan
city: Aguascalientes
country: Mexico
facility: Centro de Investigación Cardiométabolica de Aguascalientes S.A. de C.V.
city: Chihuahua
country: Mexico
facility: Cientia Investigacion Clinica Sc
city: Mexico City
country: Mexico
facility: Clinstile, S.A. de C.V.
city: Tlanepantla
country: Mexico
facility: Clinical Research Institute S.C.
city: Amsterdam
country: Netherlands
facility: Vumc Amsterdam Medical Center
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen Apeldoorn
city: Delft
country: Netherlands
facility: Reinier de Graaf Ziekenhuis
city: Dirksland
country: Netherlands
facility: Het Van Weel Bethesda ziekenhuis
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Hoogeveen
country: Netherlands
facility: Bethesda Diabetes Research Center
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis (CWZ)
city: Gdańsk
country: Poland
facility: UCK, I Klinika Kardiologii
city: Józefów
country: Poland
facility: Biokinetica
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia
city: Lublin
country: Poland
facility: Clinical Best Solutions
city: Lublin
country: Poland
facility: Etg Lublin
city: Poznan
country: Poland
facility: Centrum Zdrowia Metabolicznego
city: Warsaw
country: Poland
facility: Clinical Best Solutions Sp. Z.o.o Spolka Komandytowa
city: Warsaw
country: Poland
facility: Centrum Medycnze AMED
city: Warszawa
country: Poland
facility: Narodowy Instytut Kardiologii im. S. Wyszyńskiego - PIB
city: Zamość
country: Poland
facility: ETG Zamosc / Pro Life Medica Sp. z o.o.
city: Łódź
country: Poland
facility: Centra Medyczne Medyceusz
city: Lisboa
country: Portugal
facility: Hospital CUF Tejo
city: Santa Maria Da Feira
country: Portugal
facility: Centro Hospitalar de Entre Douro e Vouga
city: Alba
country: Romania
facility: Cabinet Medical Individual SC DIANA BARBONTA SRL
city: Baia Mare
country: Romania
facility: Cardioplus Center SRL
city: Braşov
country: Romania
facility: Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed S.R.L
city: Bucuresti
country: Romania
facility: Centrul Medical Medicover Victoria
city: Piteşti
country: Romania
facility: S.C. SAL MED S.R.L., Cardiologie
city: Târgu-Mureş
country: Romania
facility: Cardio Med SRL
city: Târgu-Mureş
country: Romania
facility: S.C. Mediab Srl
city: Bardejov
country: Slovakia
facility: Alian s.r.o.
city: Bratislava
country: Slovakia
facility: Ambulancia diabetologicka a poruch latkovej premeny a vyzivy
city: Lučenec
country: Slovakia
facility: Interna a diabetologicka ambulancia - IN-DIA s.r.o.
city: Rožňava
country: Slovakia
facility: Diab sro
city: Svidník
country: Slovakia
facility: Interna SK, s.r.o.
city: Trebišov
country: Slovakia
facility: Areteus s.r.o
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Huelva
country: Spain
facility: Hospital Comarcal Infanta Elena
city: Jaén
country: Spain
facility: Hospital Universitario de Jaen
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional de Malaga
city: Malaga
country: Spain
facility: Unidad de Ensayos Clinicos
city: Santiago De Compostela
country: Spain
facility: Hospital Provincial de Conxo
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Solna
country: Sweden
facility: Acardo MedSite
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
city: New Taipei City
country: Taiwan
facility: Mackay Memorial Hospital
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Shin Kong Wu Ho-Su Memorial Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou Branch
Study officials:
References: