Severe Hypertriglyceridemia Clinical Trial
Official title:
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Patients With Severe Hypertriglyceridemia
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.
| Status | Recruiting |
| Enrollment | 390 |
| Est. completion date | July 2025 |
| Est. primary completion date | June 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Centro Médico Dra. Laura Maffei | Buenos Aires | |
| Argentina | Glenny Corp SA | Buenos Aires | |
| Argentina | CIPREC - Centro de Investigación y Prevención Cardiovascular | Ciudad Autónoma de Buenos Aires | |
| Argentina | Fundacion Favaloro | Ciudad Autónoma de Buenos Aires | |
| Argentina | Instituto Médico DAMIC | Córdoba | |
| Argentina | Instituto de Cardiología Corrientes | Corrientes | |
| Argentina | Centro Medico San Luis | San Luis | |
| Argentina | Clínica FUSAVIM Privada | Villa María | |
| Belgium | AZ Sint-Jan Brugge | Brugge | |
| Belgium | Hôpital Erasme | Brussels | |
| Belgium | Virga Jessa Hospital | Hasselt | |
| Belgium | UZ Leuven | Leuven | |
| Brazil | NUPEC - Nucleo de Pesquisa Clinica | Belo Horizonte | |
| Brazil | Núcleo de Pesquisa Clínica | Curitiba | |
| Brazil | Hospital Universitario Walter Cantidio - UFC | Fortaleza | |
| Brazil | Nucleo de Pesquisa em Cirurgia Vascular | Porto Alegre | |
| Brazil | IBPClin Pesquisa Clinica | Rio De Janeiro | |
| Brazil | Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP | Sao Paulo | |
| Brazil | CPQuali Pesquisa Clinica | São Paulo | |
| Brazil | i9 Pesquisas Clínicas/Loema - Instituto de Pesquisas Clínica & Consultores | São Paulo | |
| Brazil | Instituto do Coração - HCFMUSP | São Paulo | |
| Bulgaria | Medical Center Diamedical EOOD | Dimitrovgrad | |
| Bulgaria | MHAT Haskovo AD | Haskovo | |
| Bulgaria | MHAT Pazardzhik AD | Pazardzhik | |
| Bulgaria | UMHAT - Kaspela EOOD | Plovdiv | |
| Bulgaria | University Multiprofile Hospital for Active Treatment Pulmed OOD | Plovdiv | |
| Bulgaria | UMHAT Kanev AD | Ruse | |
| Bulgaria | MHAT Sliven to MMA Sofia | Sliven | |
| Bulgaria | Medical Center Smolyan Clinical Research OOD | Smolyan | |
| Bulgaria | Acibadem City Clinic Tokuda University Hospital | Sofia | |
| Bulgaria | Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD | Sofia | |
| Bulgaria | Medical Centre Synexus Sofia EOOD | Sofia | |
| Bulgaria | Medico Dental Center ISUL Tsaritsa Yoanna EOOD | Sofia | |
| Bulgaria | Medical Center Zara - Med | Stara Zagora | |
| Bulgaria | DCC Equita | Varna | |
| Bulgaria | Specialized Hospital for Active Treatment of Cardiology | Varna | |
| Bulgaria | Medical Centre "Nevromedics" EOOD | Veliko Tarnovo | |
| Canada | Aggarwal and Associates Ltd. | Brampton | Ontario |
| Canada | Joanne F. Liutkus Medicine Professional Corporation | Cambridge | Ontario |
| Canada | NL Health Services | Saint John's | Newfoundland and Labrador |
| Canada | Bluewater Clinical Research Group | Sarnia | Ontario |
| Canada | Unite de Recherche Clinique | St Jerome | Quebec |
| Canada | Toronto General Hospital | Toronto | Ontario |
| Czechia | CTC Hodonin s.r.o. | Hodonín | |
| Czechia | KardioBusak s.r.o. | Louny | |
| Czechia | Fakultni nemocnice v Motole | Prague | |
| Czechia | Endokrinologie Cerny Most s.r.o. | Praha | |
| Czechia | Diabetologická a endokrinologická ambulance Milan Kvapil | Príbram | |
| Czechia | AeskuLab k.s | Teplice | |
| France | Hopital de Hautepierre | Strasbourg | |
| France | ELSAN - Polyclinique Vauban | Valenciennes | |
| France | GHM les Portes du Sud | Vénissieux | |
| Greece | University General Hospital of Alexandroupoli | Alexandroupoli | |
| Greece | AHEPA Building of Evaggelismos | Athens | |
| Greece | Hygeia Hospital | Athens | |
| Greece | University General Hospital ATTIKON | Athens | |
| Greece | AHEPA University General Hospital of Thessaloniki | Thessaloníki | |
| Hungary | Lausmed Kft. | Baja | |
| Hungary | DRC Gyogyszervizsgalo Kozpont Kft | Balatonfured | |
| Hungary | Clinexpert Kft. | Budapest | |
| Hungary | Obudai Egeszsegugyi Centrum | Budapest | |
| Hungary | Pharma4 Trial Kft. | Gyöngyös | |
| Hungary | Somogy Varmegyei Kaposi Mor Oktato Korhaz Diabetologiai szakrendeles | Kaposvár | |
| India | Sri Jayadeva Institute of Cardiovascular Sciences and Research | Bengaluru | |
| India | Sir Ganga Ram Hospital | Delhi | |
| India | Eternal Hospital | Jaipur | |
| India | B. M. Birla Heart Research Centre A Unit of the Calcutta Medical Research Institute | Kolkata | West Bengal |
| India | IPGMER | Kolkata | |
| India | Vinaya Hospital and Research Centre (A Unit of Karnataka Institute of Medical Sciences) | Mangaluru | |
| India | Bhatia Hospital | Mumbai | |
| India | KEM Hospital | Mumbai | |
| India | Manipal Hospital Mysore | Mysore | |
| India | Max Super Specialty Hospital | New Delhi | Delhi |
| Italy | Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII | Bergamo | |
| Italy | AORN S. Anna e S. Sebastiano UOC FARMACIA | Caserta | |
| Italy | Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna | Cona | |
| Italy | Fondazione I.R.C.C.S. Policlinico "San Matteo" c/o C.U.R.M. | Pavia | |
| Lithuania | Pirmoji viltis | Šiauliai | |
| Lithuania | Klinikiniai sprendimai | Kaunas | |
| Lithuania | Saules seimons medicinos centras | Kaunas | |
| Lithuania | Clinic of Cardiology and Rehabilitation | Klaipeda | |
| Lithuania | Republican Panevezys Hospital | Panevežys | |
| Malaysia | Sultanah Bahiyah Hospital | Alor Setar | Kedah |
| Malaysia | Pulau Pinang Hospital | George Town | Pulau Pinang |
| Malaysia | University Malaya Medical Centre (UMMC) | Kuala Lumpur | |
| Malaysia | Hospital Taiping | Taiping | Perak |
| Mexico | Centro de Investigación Cardiométabolica de Aguascalientes S.A. de C.V. | Aguascalientes | |
| Mexico | Cientia Investigacion Clinica Sc | Chihuahua | |
| Mexico | Medical Care and Research S.A de C.V. | Mérida | Yucatan |
| Mexico | Clinstile, S.A. de C.V. | Mexico City | |
| Mexico | Clinical Research Institute S.C. | Tlanepantla | |
| Netherlands | Vumc Amsterdam Medical Center | Amsterdam | |
| Netherlands | Gelre Ziekenhuizen Apeldoorn | Apeldoorn | |
| Netherlands | Reinier de Graaf Ziekenhuis | Delft | |
| Netherlands | Het Van Weel Bethesda ziekenhuis | Dirksland | |
| Netherlands | Albert Schweitzer Ziekenhuis | Dordrecht | |
| Netherlands | Bethesda Diabetes Research Center | Hoogeveen | |
| Netherlands | Canisius-Wilhelmina Ziekenhuis (CWZ) | Nijmegen | |
| Poland | UCK, I Klinika Kardiologii | Gdansk | |
| Poland | Biokinetica | Józefów | |
| Poland | Centrum Medyczne Pratia | Katowice | |
| Poland | Centra Medyczne Medyceusz | Lódz | |
| Poland | Clinical Best Solutions | Lublin | |
| Poland | Etg Lublin | Lublin | |
| Poland | Centrum Zdrowia Metabolicznego | Poznan | |
| Poland | Centrum Medycnze AMED | Warsaw | |
| Poland | Clinical Best Solutions Sp. Z.o.o Spolka Komandytowa | Warsaw | |
| Poland | Narodowy Instytut Kardiologii im. S. Wyszynskiego - PIB | Warszawa | |
| Poland | ETG Zamosc / Pro Life Medica Sp. z o.o. | Zamosc | |
| Portugal | Hospital CUF Tejo | Lisboa | |
| Portugal | Centro Hospitalar de Entre Douro e Vouga | Santa Maria Da Feira | |
| Romania | Cabinet Medical Individual SC DIANA BARBONTA SRL | Alba | |
| Romania | Cardioplus Center SRL | Baia Mare | |
| Romania | Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed S.R.L | Brasov | |
| Romania | Centrul Medical Medicover Victoria | Bucuresti | |
| Romania | S.C. SAL MED S.R.L., Cardiologie | Pitesti | |
| Romania | Cardio Med SRL | Târgu-Mures | |
| Romania | S.C. Mediab Srl | Târgu-Mures | |
| Slovakia | Alian s.r.o. | Bardejov | |
| Slovakia | Ambulancia diabetologicka a poruch latkovej premeny a vyzivy | Bratislava | |
| Slovakia | Interna a diabetologicka ambulancia - IN-DIA s.r.o. | Lucenec | |
| Slovakia | Diab sro | Rožnava | |
| Slovakia | Interna SK, s.r.o. | Svidník | |
| Slovakia | Areteus s.r.o | Trebišov | |
| Spain | Hospital Germans Trias i Pujol | Badalona | |
| Spain | Hospital Vall d'Hebron | Barcelona | |
| Spain | Hospital Comarcal Infanta Elena | Huelva | |
| Spain | Hospital Universitario de Jaen | Jaén | |
| Spain | Hospital Universitario 12 de Octubre | Madrid | |
| Spain | Hospital Regional de Malaga | Malaga | |
| Spain | Unidad de Ensayos Clinicos | Malaga | |
| Spain | Hospital Provincial de Conxo | Santiago De Compostela | |
| Spain | Hospital Universitario Virgen Macarena | Sevilla | |
| Spain | Hospital Clinico Universitario de Valencia | Valencia | |
| Spain | Hospital Universitario Miguel Servet | Zaragoza | |
| Sweden | Acardo MedSite | Solna | |
| Taiwan | Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH) | Kaohsiung | |
| Taiwan | Mackay Memorial Hospital | New Taipei City | |
| Taiwan | Taichung Veterans General Hospital | Taichung City | |
| Taiwan | National Cheng Kung University Hospital | Tainan | |
| Taiwan | Shin Kong Wu Ho-Su Memorial Hospital | Taipei City | |
| Taiwan | Chang Gung Medical Foundation - Linkou Branch | Taoyuan | |
| United States | Emory University | Atlanta | Georgia |
| United States | Maryland Cardiovascular Specialists | Baltimore | Maryland |
| United States | University of Maryland School of Medicine | Baltimore | Maryland |
| United States | Alabama Clinical Therapeutics, LLC Alabaster | Birmingham | Alabama |
| United States | Central Research Associates, Inc. | Birmingham | Alabama |
| United States | Grace Research, LLC | Bossier City | Louisiana |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | St. Vincent Medical Group | Carmel | Indiana |
| United States | Medical University of South Carolina (MUSC) | Charleston | South Carolina |
| United States | The Ohio State University (OSU) | Columbus | Ohio |
| United States | Accel Research Sites | DeLand | Florida |
| United States | Accel Clinical Research | Eatonton | Georgia |
| United States | Onyx Clinical Research | Flint | Michigan |
| United States | Texas Health Family Care | Fort Worth | Texas |
| United States | Northeast Georgia Medical Center | Gainesville | Georgia |
| United States | Finlay Medical Research | Greenacres City | Florida |
| United States | Clinical Trial Network | Houston | Texas |
| United States | Juno Research | Houston | Texas |
| United States | Juno Research | Houston | Texas |
| United States | Pioneer Research Solutions, Inc | Houston | Texas |
| United States | Vilo Research Group | Houston | Texas |
| United States | The Jackson Clinic | Jackson | Tennessee |
| United States | University of Florida Jacksonville | Jacksonville | Florida |
| United States | University of Kansas Medical Center (KUMC) | Kansas City | Kansas |
| United States | Clinical Investigation Specialists Inc. | Kenosha | Wisconsin |
| United States | Sante Clinical Research, LLC | Kerrville | Texas |
| United States | FMC Science | Lampasas | Texas |
| United States | Clinical Trials of America, LLC | Lenoir | North Carolina |
| United States | The Research Group of Lexington, LLC | Lexington | Kentucky |
| United States | Main Street Physicians Care Waterway | Little River | South Carolina |
| United States | NRC Research Institute | Los Angeles | California |
| United States | Louisville Metabolic and Atherosclerosis Research Center (L-MARC) | Louisville | Kentucky |
| United States | University of Louisville | Louisville | Kentucky |
| United States | Meridien Research | Maitland | Florida |
| United States | SV Research LLC | Marion | Ohio |
| United States | DCT - McAllen Primary Care, LLC | McAllen | Texas |
| United States | McAllen Primary Care, LLC | McAllen | Texas |
| United States | Texas Institute of Cardiology | McKinney | Texas |
| United States | SMS Clinical Research, LLC | Mesquite | Texas |
| United States | Southern Endocrinology Associates | Mesquite | Texas |
| United States | Columbus Clinical Services | Miami | Florida |
| United States | NYU Langone Hospital - Long Island | Mineola | New York |
| United States | Clinical Trials of America LA, LLC | Monroe | Louisiana |
| United States | Diabetes and Endocrinology Consultants, P.C. | Morehead City | North Carolina |
| United States | Randomize Now | Newnan | Georgia |
| United States | Harmony Clinical Research, Inc | North Miami Beach | Florida |
| United States | Permian Research Foundation | Odessa | Texas |
| United States | Orchard Park Family Practice | Orchard Park | New York |
| United States | Aspen Clinical Research | Orem | Utah |
| United States | Combined Research Orlando Phase I-IV | Orlando | Florida |
| United States | Onyx Clinical Research | Peoria | Arizona |
| United States | University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Monument Health Clinical Research | Rapid City | South Dakota |
| United States | Onyx Clinical Research | Rochester Hills | Michigan |
| United States | Ogden Clinic Grandview | Roy | Utah |
| United States | OnSite Clinical Solutions, LLC | Salisbury | North Carolina |
| United States | Diabetes & Glandular Disease Clinic, P.A. | San Antonio | Texas |
| United States | Stern Cardiovascular | Southaven | Mississippi |
| United States | 3Sync Research | Sunrise | Florida |
| United States | JSV Clinical Research Study, Inc. | Tampa | Florida |
| United States | R & B Medical Center LLC | Tampa | Florida |
| United States | Oklahoma Heart Institute | Tulsa | Oklahoma |
| United States | Tranquil Research | Webster | Texas |
| United States | Metabolic Research Institute | West Palm Beach | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Ionis Pharmaceuticals, Inc. |
United States, Argentina, Belgium, Brazil, Bulgaria, Canada, Czechia, France, Greece, Hungary, India, Italy, Lithuania, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Slovakia, Spain, Sweden, Taiwan,
| 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 Month 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 Month 12 | ||
| Secondary | Percentage of Participants Achieving Fasting TG < 1000 mg/dL in Participants with Baseline TG = 1000 mg | 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 Month 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 | 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 |
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