Severe HypertriglyceridemiaPhase 3NCT05681351
CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)
A Phase 3 study testing Olezarsen in people with Severe Hypertriglyceridemia, run by Ionis Pharmaceuticals, Inc. at 262 sites in 33 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of olezarsen in participants with SHTG. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Hypertriglyceridemia
- What is being tested?
- Olezarsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 885 participants
- Where
- 262 sitesin 33 countries
- Study dates
- 13 Dec 2022to Mar 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Satisfactory completion of either ISIS 678354-CS5 or ISIS 678354-CS6 with an acceptable safety profile, per Investigator judgment. Satisfactory completion requires that the patient did not terminate early from treatment.
- Participants must be on a stable regimen of lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. A patient may be eligible if their regimen of lipid-lowering therapy has been changed recently, provided that lipid lowering medications are optimized and stabilized for at least 4 weeks prior to the end of the Qualification Period of this OLE study; ideally, such changes are initiated after Week 53 of the index study (ISIS 678354-CS5 or CS6).
- A patient may re-enroll in the study after having completed the study when the Treatment Period was 53 weeks, if the patient satisfactorily completed the study with an acceptable safety profile, per Investigator judgment. In the case of re-enrollment, there is no limit on the time gap between completion of treatment under the previous protocol and dosing upon re-enrollment (i.e., may exceed 17 weeks between doses).
Who cannot join
- Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study, including need for treatment with disallowed medications, or need to change the required stable regimen as per either ISIS 678354-CS5 or ISIS 678354-CS6 study entry criteria. It is acceptable to adjust a regimen of lipid-lowering therapy as described in the second Key Inclusion Criterion above, and it is acceptable to adjust or stop lipid-lowering therapy at or after Week 13 per Investigator judgment.
- NOTE: Other Inclusion/Exclusion criteria may apply.
Trial locations and contacts
262 sites in 33 countries.
262 sites in 33 countries
United States65 sites
University of Michigan- Endocrinology & Metabolism
Ann Arbor, Michigan, 48109
University of Maryland School of Medicine
Baltimore, Maryland, 21201
Excel Medical Clinical Trials
Boca Raton, Florida, 33434
Grace Research, LLC
Bossier City, Louisiana, 71111
Massachusetts General Hospital Heart Center
Boston, Massachusetts, 02114
Modern Medical
Brooklyn, New York, 33709
St. Vincent Medical Group, Inc.
Carmel, Indiana, 46290
Medical University of South Carolina
Charleston, South Carolina, 29425
The Presbyterian Hospital DBA Novant Health Heart and Vascular Institute
Charlotte, North Carolina, 28204
Chattanooga Research & Medicine, PLLC
Chattanooga, Tennessee, 37404
Centricity Research
Columbus, Georgia, 31904
IACT Health
Columbus, Georgia, 31904
The Ohio State University
Columbus, Ohio, 43203
University of Texas Southwestern
Dallas, Texas, 75390
Central Oklahoma Early Detection Center
Edmond, Oklahoma, 73034
Aa Mrc, Llc
Flint, Michigan, 48504
Finlay Medical Research
Greenacres City, Florida, 33467
Kenneth Hilty
Greensboro, North Carolina, 27401
Baylor College of Medicine
Houston, Texas, 77030
Juno Research
Houston, Texas, 77040
Pioneer Research Solutions
Houston, Texas, 77099
The Jackson Clinic
Jackson, Tennessee, 38301
University of Kansas Medical Center (KUMC)
Kansas City, Kansas, 66160
Sante Clinical Research LLC
Kerrville, Texas, 78028
FMC Science
Lampasas, Texas, 76550
Palm Research Center, Inc.
Las Vegas, Nevada, 89128
Clinical Trials of America, LLC
Lenoir, North Carolina, 28645
The Research Group of Lexington, LLC
Lexington, Kentucky, 40503
Bryan Medical Center
Lincoln, Nebraska, 68506
Walker Family Care
Little River, South Carolina, 29566
LA Universal Research Center, Inc.
Los Angeles, California, 90057
Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
Louisville, Kentucky, 40213
Manassas Clinical Research
Manassas, Virginia, 20110
DCT- McAllen Primary Care, LLC
McAllen, Texas, 78503
Texas Institute of Cardiology
McKinney, Texas, 75071
SMS Clinical Research, LLC
Mesquite, Texas, 75149
Southern Endocrinology Associates
Mesquite, Texas, 75149
Columbus Clinical Services, LLC
Miami, Florida, 33125
Finlay Medical Research
Miami, Florida, 33126
NYU Langone Health
Mineola, New York, 11501
Innovia Research Center, Inc.
Miramar, Florida, 33027
WVU Heart and Vascular Institute
Morgantown, West Virginia, 26506
Langone Medical Center
New York, New York, 10016
Vagelos College of Physicians and Surgeons of Columbia University
New York, New York, 10032
York Clinical Research
Norfolk, Virginia, 23510
Harmony Clinical Research, Inc.
North Miami Beach, Florida, 33162
Affinity Health
Oak Brook, Illinois, 60523
Permian Research Foundation
Odessa, Texas, 79761
Orchard Park Family Practice
Orchard Park, New York, 14127
University of Pennsylvania
Philadelphia, Pennsylvania, 19014
Monument Health Clinical Research
Rapid City, South Dakota, 57701
Health Concepts
Rapid City, South Dakota, 57702
Diabetes & Glandular Disease Clinic, P.A.
San Antonio, Texas, 78229
University of California, San Diego (UCSD)
San Diego, California, 92161
Washington School of Medicine
St Louis, Missouri, 63110
R & B Medical Center LLC
Tampa, Florida, 33614
VICIS Clinical Research
Tampa, Florida, 33615
JSV Clinical Research Study, Inc.
Tampa, Florida, 33634
Metabolic Institute of America
Tarzana, California, 91356
IRC Clinics
Towson, Maryland, 21204
Bayside Clinical Research
Trinity, Florida, 34655
Oklahoma Heart Institute
Tulsa, Oklahoma, 74104
Hudson County Clinical Trials Research Center
Union City, New Jersey, 07087
Tranquil Clinical and Research Consulting Services
Webster, Texas, 77598
Lexington
Winston-Salem, North Carolina, 27103
Bulgaria26 sites
MHAT- Blagoevgrad AD
Blagoevgrad, 2700
Medical Center Doctor Staykov EOOD
Burgas, 8000
Medical Center Diamedical 2013 OOD
Dimitrovgrad, 6400
MHAT
Gabrovo, 5300
MHAT Haskovo AD
Haskovo, 6300
Multiprofile Hospital for Active Treament Pazardzhik, Cardiology Department
Pazardzhik, 4400
SBAL "Special Medic" Ltd.
Plovdiv, 4000
UHMAT Kaspela Ltd
Plovdiv, 4001
University Multiprofile Hospital for Active Treatment Pulmed, Clinic of Endocrinology
Plovdiv, 4002
Medical Center Rusemed EOOD
Rousse, 7000
UMHAT Kanev AD
Rousse, 7002
DCC-1 Sliven Ltd.
Sliven, 8800
Medical Center Smolyan Clinical Research OOD
Smolyan, 4700
Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD
Sofia, 1000
UMHAT Tsaritsa Yoanna ISUL- Clinic of Cardiology
Sofia, 1527
Medical Center Endomedical
Sofia, 1606
Medical Center Kalimat EOOD
Sofia, 1680
MC Doctor Kalchev OOD
Sofia, 1700
Medical Centre Synexus Sofia
Sofia, 1784
UMHAT Sofiamed
Sofia, 1797
MHAT Silven to MMA Sofia
Sofia, 8800
Clinical of Cardiology
Stara Zagora, 6003
Medical Center Zara-Med
Stara Zagora, 6010
Diagnostic Consultative Center Equita (DCC Equita)
Varna, 9000
Specialized Hospital for Active Treatment of Cardiology
Varna, 9020
Medical Centre "Nevromedics" EOOD
Veliko Tarnovo, 5006
Spain15 sites
Hospital Abente y Lago
A Coruña, 15001
Hospital Germans Trias i Pujol
Badalona, 08916
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Clinic De Barcelona
Barcelona, 08036
Hospital Universitari de Bellvitge
Barcelona, 8907
Hospital Universitario Reina Sofia
Córdoba, 14004
Hospital Universitario de Jaen
Jaén, 23007
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Corporacio Sanitaria Parc Tauli- Hospital de Sabadell
Sabadell, 08208
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Virgen del Rocío
Seville, 41013
Hospital Universitari Sant Joan de Reus
Tarragona, 43204
Hospital Clinico Universitario de Valencia
Valencia, 46010
Hospital Universitario Miguel Servet
Zaragoza, 50009
Czechia12 sites
MEDICUS SERVICES s.r.o.
Brandýs nad Labem, 250 01
University Hospital Hradec Králové
Hradec Králové, 50005
KardioBusak s.r.o.
Louny, 440 01
EDUMED s.r.o.
Náchod, 547 01
Fakultni nemocnice Ostrava
Ostrava, 70852
Vseobecna fakultni nemocnice
Prague, 128 08
Fakultni Nemocnice v Motole
Prague, 15006
Praha Poliklinika Hurka
Prague, 158 00
Endokrinologie Cerny Most s.r.o.
Prague, 19800
Milan Kvapil s.r.o.
Příbram, 261 01
AeskuLab k.s
Teplice, 415 01
MU Dr. Nina Zemkova s.r.o. Interni Ambulance
Uherské Hradiště, 686 01
Poland11 sites
Uniwersytecki Centrum Kliniczne, I Klinika Kardiologii
Gdansk, 80-952
Biokinetica Spolka Akcujna
Józefów, 05-410
Centrum Medyczne Salvia
Katowice, 40-772
Instytut Centrum Zdrowia Matki Polki
Lodz, 93-338
Clinical Best Solutions
Lublin, 20-078
ETG Lublin
Lublin, 20-412
Centrum Zdrowia Metabolicznego Pawel Bogdanski
Poznan, 60-589
Osrodek Badan Klinicznych Metabolica
Tarnów, 33-100
Clinical Best Solutions Sp. z.o.o. Spolka Komandytowa
Warsaw, 02-793
Przychodnia Futuremeds Wroclaw
Wroclaw, 50-088
ETG Zamosc
Zamość, 22-400
Netherlands10 sites
Academic Medical Center
Amsterdam, 1105AZ
Gelre Ziekenhuizen
Apeldoorn, 7334 DZ
Ziekenhuis Rijnstate
Arnhem, 6815 AD
Het Van Weel-Bethesda Ziekenhuis
Dirksland, 3247 BW
Ziekenhuis Gelderse Vallei
Ede, 1001-5000
Bethesda Diabetes Research Center
Hoogeveen, 7909 AA
Radboud UMC
Nijmegen, 6525 EX
Erasmus MC
Rotterdam, 3015 GD
University Medical Center Utrecht
Utrecht, 3584 CX
Albert Schweitzer Ziekenhuis
Zwijndrecht, 3331 LZ
Slovakia10 sites
Ambulancia diabetologicka a poruch latkovej premeny a vyzivy
Bratislava, 831 06
Kardiologická ambulancia
Brezno, 97701
Cardio D&R, S.R.O. Kosice
Košice, 040 22
Human-Care s.r.o.
Košice, 04001
Vychodoslovensky Utsav srdcovych a cievnych chorob a.s.
Košice, 04011
Interna a diabetologicka ambulancia- IN- DRA- s.r.o.
Lučenec, 984 01
Diab sro
Rožňava, 048 01
Interna SK, s.r.o., Kardiologicka a interna ambulancia
Svidník, 08901
Nemocnica arm. generala L. Svobodu Svidnik, a.s
Svidník, 08901
Areteus sro
Trebišov, 075 01
France9 sites
Louis Pradel Hospital
Bron, 69500
Chu Dijon Bourgogne
Dijon, 21079
Hôpitaux de Marseille
Marseille, 13005
Hopital Lapeyronie
Montpellier, 34295
AP-HP Hopital Pitie-Salpetriere
Paris, 75013
CHU de Nantes - Hôpital Nord Laennec
Saint-Herblain, 44093
CHRU de Strasbourg
Strasbourg, 67200
Groupement de Cooperation Sanitaire (GCS) ESLAN - Polyclinique Vauban
Valenciennes, 59300
GHM les Portes du Sud
Vénissieux, 69200
United Kingdom9 sites
Waterloo Medical Care
Blackpool, FY4 3AD
Huddersfield Royal Infirmary
Huddersfield, England, HD3 3EA
Hull Royal Infirmiry
Hull, HU3 2JZ
Oak Tree Surgery and Pensilva Health Centre
Liskeard, PL14 3XA
Manchester University NHS Foundation Trust
Manchester, M13 9WL
Newquay Health Centre
Newquay, TR7 1RQ
The Adam Practice
Poole, BH16 5PW
Sandwell and West Birmingham NHS Trust
West Bromwich, B71 4HU
Centre for Diabetes, Endocrinology and Metabolic Disease
Woodhurst, Chatsworth, 4092
Hungary8 sites
Lausmed Kft
Baja, 6500
DRC Gyógyszervizsgáló Központ Korlátolt felelősségű társaság Balatonfüred
Balatonfüred, 8230
Obudai Egeszsegugyyi Centrum
Budapest, H-1063
Debreceni Egyetem Klinikai Központ
Debrecen, 4032
Rakoczi Ferenc Korhaz
Miskolc, H-3529
Dr. Vasas Szilard Haziorvosi Rendelo
Nyíregyháza, 4405
Kardiologia Szakrendeles
Nyíregyháza, H-4400
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
Székesfehérvár, 8000
Israel8 sites
Soroka Medical Center
Beersheba, 8410101
Bnai Zion Medical Center
Haifa, 3104802
The Lady Davis Carmel Medical Center
Haifa, 3436212
Shaare Zedek Medical Center
Jerusalem, 9103102
Rabin Medical Center
Petah Tikva, 4941492
The Chaim Sheba Medical Center
Ramat Gan, 52621
Kaplan Medical Center
Rehovot, 76100
Tel Aviv Sourasky Medical Center
Tel Aviv
Italy8 sites
Azienda Socio Sanitaria Territoriale Papa Giovanni XXII
Bergamo, 24127
Policlinico di Sant'Orsola
Bologna, 40138
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione "Sant' Anna e San Sebastiano" di Caserta
Caserta, 81100
Ospdale E. Bassini
Milan, 20092
Asst Grande Ospedale Metropolitano Niguarda
Milan, 20162
Azienda Ospedaliera Universitaria Federico II
Naples, 80131
Azienda Ospedaliera Universitaria Policlinico
Palmero, 90127
Department of Translational and Precision Medicine
Rome, 00161
Brazil7 sites
Centro Especializado em Cardiologia
Campinas, 13010-001
Nucleo de Pesquisa Clinica S/S
Curitiba, 80730-150
Hospital Universitario Walter Cantidio- UFC
Fortaleza, 60430-270
Nucleo de Pasquisa em Cirurgia Vascular
Porto Alegre, 90035-903
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo- FMUSP
São Paulo, 05403-000
Instituto do Coracao (InCor) do Hospital das Clinicas da FMUSP
São Paulo, CEP-05403-000
CPQuali Pesquisa Clinica Ltda.
São Paulo, SP-01228-00
Argentina6 sites
CIPREC
Buenos Aires, C1061
Fundacion Favaloro
Buenos Aires, C1093AAS
Centro Medico Dra. Laura Maffei-Investigacion Clinica Aplicad
Buenos Aires, C1425AGC
Glenny Corp SA
Buenos Aires, C1430CKE
Instituto Medico DAMIC
Córdoba, X5003DCE
Clinica FUSAVIM Privada
Villa María, X5900JKA
Canada6 sites
Ecogene-21
Chicoutimi, Quebec, G7H 7K9
Institut de Recherches Cliniques de Montreal
Montreal, H2W 1T7
Clinique des Maladies Lipidiques de Quebec Inc.
Québec, Quebec, G1V 4W2
Bluewater Clinical Research Group, Inc.
Sarnia, Ontario, N7T 4X3
Canadian Phase Onward Inc.
Toronto, Ontario, M3J2C5
Toronto General Hospital
Toronto, M4C 3E7
Australia5 sites
Royal Adelaide Hospital
Adelaide, 5000
Royal Prince Alfred Hospital
Camperdown, 2050
Monash Medical Centre
Clayton, 3168
Royal North Shore Hospital
Saint Leonards, New South Wales, 2065
Dr Heart Pty Ltd
Woolloongabba, 4102
Portugal5 sites
Hospital Infante D. Pedro
Aveiro, 3814-501
Hospital COF Tejo
Lisbon, 1350-352
Hospital CUF Tejo
Lisbon, 1350-352
Centro Hospitalar Universitario De Sao Joao
Porto, 4200-319
Centro Hospitalar de Entre o Douro e Vouga, E.P.E.
Santa Maria da Feira, 4520-211
Taiwan5 sites
Kaohsiung Medical University Ching-Ho Memorial Hospital
Kaohsiung City, 80756
Mackay Memorial Hospital
New Taipei City, 25160
Taichung Veterans General Hospital
Taichung, 40705
National Cheng Kung University Hospital
Tainan, 704
Shing Kong Wu Ho-Su Memorial Hospital
Taipei, 111
Denmark4 sites
Aalborg University Hospital
Aalborg, 9000
Aarhus Universitet Hospital
Aarhus, 8200
Esbjerg Hospital
Esbjerg, 6700
Viborg Regional Hospital
Viborg, 8800
Germany4 sites
Charite- Universitaetsmedizin Berlin
Berlin, 13353
Universitaetsklinikum Koeln
Cologne, 50937
Universitaetsklinikum Carl Gustav Carus
Dresden, 1307
Forschungszentrum Ruhr
Witten, 58455
South Africa4 sites
Latros International
Bloemfontein, 9301
Medi Clinic Vergelegen
Cape Town, 7130
TREAD Research
Cape Town, 7500
University of Cape Town
Cape Town, 7700
Belgium3 sites
Universite Libre de Brussels (ULB)- Hopital Erasme
Brussels, 1070
Jessa Ziekenhuis
Hasselt, 3500
Universitaire Ziekenhuizen Leuven
Leuven, 3000
Lithuania3 sites
Klinikiniai Sprendimai, UAB
Kaunas, 49387
Saules Seimos Medicinos Centras
Kaunas, 49456
Kardiologijos ir reabilitacijos klinika, UAB
Klaipėda, 91131
Mexico3 sites
Scientia Investigacion Clinical Sc
Chihuahua City, 31207
Clinstile, S.A. de C.V.
Mexico City, 06700
Centro de Investigacion Cardiometabolica S.C.
Mexico City, 20230
Turkey (Türkiye)3 sites
Ege University School of Medicine, Department of Cardiology
Izmir, 35040
Necmettin Erbakan Universitesi Meram Tip Fakultesi
Konya, 42080
Hacettepe Üniversitesi Tıp Fakültesi
Sulhiye, 06100
Greece2 sites
Evangelismos General Hospital Athens
Athens, 106 76
Hygeia Hospital
Athens, 15123
India2 sites
Vinaya Hospital and Research Centre
Mangalore, 575003
Sir Ganga Ram Hospital
New Delhi, 110060
Malaysia2 sites
University Malaya Medical Centre (UMMC)
Kuala Lumpur, 59100
Pulau Pinang Hospital
Pulau Pinang, 10990
New Zealand2 sites
New Zealand Clinical Research
Auckland, 8011
Edgar Diabetes and Obesity Research Centre
Wellington, 6021
Sweden2 sites
Sahlgrenska, University Hospital
Gothenburg, 413 45
Karolinska University Hospital Huddinge
Stockholm, 14186
About this study
Official title: An Open-Label Extension Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Patients With Severe Hypertriglyceridemia (SHTG)
The purpose of this study is to evaluate the safety and tolerability of olezarsen in participants with SHTG.
Read the detailed description
This is a multi-center, open-label extension (OLE) study of approximately 800 participants with SHTG who would be rolled over from studies ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326). Day 1 of this study may be same as the Week 53 visit of either ISIS 678354-CS5 or ISIS 678354-CS6, as applicable. Participants will receive olezarsen during the 157-week treatment period. The study will include a 31-day qualification Period, a 157-week treatment period, and a 13-week post-treatment period.
- Conditions
- Severe Hypertriglyceridemia
- Being tested
- Olezarsen
- Keywords
- ISIS 678354, Olezarsen
- Medical subject headings
- Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlezarsenDrug
Also called AKCEA-APOCIII-LRx, ISIS 678354
Administered as SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Olezarsen | Experimental | Participants who completed either ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326) study would be enrolled to receive olezarsen, subcutaneous (SC) injection, once every 4 weeks from Week 1 through Week 153. Receives: Drug: Olezarsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants With Change in Clinical Laboratory Values From Baseline to Week 53, From Baseline to Week 105, and From Baseline to Week 157
Measured: Baseline up to Week 157
Proportion of Participants Who Experience Adverse Events (AEs)
Measured: Baseline up to Week 157
Proportion of Participants Who Use Concomitant Medications
Measured: Baseline up to Week 157
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2023
- Study start13 Dec 2022
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe HypertriglyceridemiaStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 885 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05681351
- Sponsor's protocol ID
- ISIS 678354-CS15
- Other IDs
- 2022-501999-26-00
- Status last verified
- Nov 2025
- First submitted
- 25 Dec 2022
- Last updated
- 1 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Patients With Severe Hypertriglyceridemia (SHTG)
- ClinicalTrials.gov ID
- NCT05681351
- Acronym / sponsor ID
- ISIS 678354-CS15
- Conditions
- Severe Hypertriglyceridemia
- Keywords
- ISIS 678354, Olezarsen
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 885 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Dec 2022 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 12 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability of olezarsen in participants with SHTG.
Detailed description
This is a multi-center, open-label extension (OLE) study of approximately 800 participants with SHTG who would be rolled over from studies ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326). Day 1 of this study may be same as the Week 53 visit of either ISIS 678354-CS5 or ISIS 678354-CS6, as applicable. Participants will receive olezarsen during the 157-week treatment period. The study will include a 31-day qualification Period, a 157-week treatment period, and a 13-week post-treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olezarsen | Experimental | Drug: OlezarsenParticipants who completed either ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326) study would be enrolled to receive olezarsen, subcutaneous (SC) injection, once every 4 weeks from Week 1 through Week 153. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Satisfactory completion of either ISIS 678354-CS5 or ISIS 678354-CS6 with an acceptable safety profile, per Investigator judgment. Satisfactory completion requires that the patient did not terminate early from treatment.
- Participants must be on a stable regimen of lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. A patient may be eligible if their regimen of lipid-lowering therapy has been changed recently, provided that lipid lowering medications are optimized and stabilized for at least 4 weeks prior to the end of the Qualification Period of this OLE study; ideally, such changes are initiated after Week 53 of the index study (ISIS 678354-CS5 or CS6).
- A patient may re-enroll in the study after having completed the study when the Treatment Period was 53 weeks, if the patient satisfactorily completed the study with an acceptable safety profile, per Investigator judgment. In the case of re-enrollment, there is no limit on the time gap between completion of treatment under the previous protocol and dosing upon re-enrollment (i.e., may exceed 17 weeks between doses).
Key exclusion criteria (2 listed)
- Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study, including need for treatment with disallowed medications, or need to change the required stable regimen as per either ISIS 678354-CS5 or ISIS 678354-CS6 study entry criteria. It is acceptable to adjust a regimen of lipid-lowering therapy as described in the second Key Inclusion Criterion above, and it is acceptable to adjust or stop lipid-lowering therapy at or after Week 13 per Investigator judgment.
- NOTE: Other Inclusion/Exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlezarsenAlso: AKCEA-APOCIII-LRx, ISIS 678354Administered as SC injection. | Drug | Olezarsen |
Primary outcome
Proportion of Participants With Change in Clinical Laboratory Values From Baseline to Week 53, From Baseline to Week 105, and From Baseline to Week 157
Time frame: Baseline up to Week 157
Proportion of Participants Who Experience Adverse Events (AEs)
Time frame: Baseline up to Week 157
Proportion of Participants Who Use Concomitant Medications
Time frame: Baseline up to Week 157
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2025.
- Individual participant dataSharing planned: Yes. Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
262 sites in 33 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Olezarsen in people with Severe Hypertriglyceridemia, run by Ionis Pharmaceuticals, Inc. at 262 sites in 33 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 262 sites in United States, Bulgaria, Spain, Czechia, Poland and 28 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants With Change in Clinical Laboratory Values From Baseline to Week 53, From Baseline to Week 105, and From Baseline to Week 157 (time frame: Baseline up to Week 157). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2025.