A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia

Severe Hypertriglyceridemia Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 678354 Administered Subcutaneously to Patients With Severe Hypertriglyceridemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05079919
• Other study ID #: ISIS 678354-CS5
• Secondary ID: 2021-002192-19
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 25, 2021
• Est. completion date: July 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 efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

Description:

This is a multi-center, randomized, double-blind, placebo-controlled study in up to approximately 540 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 617
• Est. completion date: July 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  New Zealand,  Norway,  Poland,  Portugal,  Slovakia,  South Africa,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from Baseline in Fasting TG at 6 Months (Average of Weeks 25 and 27) Compared to Placebo		Baseline and Month 6
Secondary	Percent Change from Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) Compared to Placebo		Baseline and Month 12
Secondary	Proportion of Participants Who Achieve Fasting TG Less Than (<) 500 milligrams per deciliter (mg/dL) (5.7 millimoles per liter [mmol/L]) at 6 and 12 Months Compared to Placebo		Month 6 and 12
Secondary	Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG = 880 mg/dL		Month 6 and 12
Secondary	Proportion of Participants Who Achieve Fasting TG < 1000 mg/dL (11.29 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG = 1000 mg/dL		Month 6 and Month 12
Secondary	Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III) at 6 and 12 Months Compared to Placebo		Baseline, Month 6 and 12
Secondary	Percent Change from Baseline in Fasting Very Low-Density Lipoprotein Cholesterol (VLDL-C) at 6 and 12 Months Compared to Placebo		Baseline, Month 6 and 12
Secondary	Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 6 and 12 Months Compared to Placebo		Baseline, Month 6 and 12
Secondary	Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at 6 and 12 Months Compared to Placebo		Baseline, Month 6 and 12
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