A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)
- Conditions
- Familial Chylomicronemia Syndrome
- Interventions
- Drug: Placebo
- Registration Number
- NCT04568434
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose of the study was to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.
- Detailed Description
This was a multi-center, double-blind, Phase 3 study in up to 60 patients with FCS. Participants were randomized in a 2:1 ratio to receive Olezarsen or matching placebo in a 53-week treatment period. The length of participation in the study was approximately 74 weeks, which included an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period. Following the treatment period, eligible patients had the option to enroll in the Open-label Extension (OLE) Study ISIS 678354-CS13 (NCT05130450).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 66
- A diagnosis of genetically confirmed Familial Chylomicronemia Syndrome (type 1 Hyperlipoproteinemia)
- Fasting TG ≥ 880 mg/dL (10 millimoles per liter (mmol/L) at Screening
- History of pancreatitis. Patients without a documented history of pancreatitis are also eligible but their enrollment will be capped at 35%
- Stable doses of statins, omega-3 fatty acids, fibrates, or other lipid-lowering medications are allowed
Key
- Acute coronary syndrome within 6 months of Screening
- Major surgery within 3 months of Screening
- Have any other conditions, which, in the opinion of the Investigator would make the participant unsuitable for inclusion, or could interfere with participating in or completing the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received olezarsen-matching placebo, once every 4 weeks by subcutaneous (SC) injection, during Weeks 1 to 49 of the 53-week treatment period. Olezarsen 50 mg Olezarsen Participants received olezarsen, 50 milligrams (mg), once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period. Olezarsen 80 mg Olezarsen Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Fasting TG at Month 6 Baseline, Month 6
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Fasting TG at Month 12 Baseline, Month 12 Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 Baseline, Months 6 and 12 Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6 Month 6 Percentages are rounded off to the nearest single decimal place.
Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 Baseline, Months 6 and 12 Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 Baseline, Months 6 and 12 Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) in Participants With Prior History of Pancreatitis During the treatment period Week 1 through Week 53 All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the Acute Pancreatitis Adjudication Committee (PAC) Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) During the treatment period Week 1 through Week 53 All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.
Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis Week 13 through Week 53 All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53 Week 13 through Week 53 All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.
Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6 Month 6 Percentages are rounded off to the nearest single decimal place.
Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6 Month 6 Percentages are rounded off to the nearest single decimal place.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment During the treatment period Week 1 through Week 53 All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years From Week 13 to Week 53 in Participants With ≥ 2 Events in 5 Years Prior to Enrollment Week 13 to Week 53 All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.
Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6 Month 6 Percentages are rounded off to the nearest single decimal place.
Trial Locations
- Locations (47)
Hospital da Senhora da Oliveira - Guimaraes
🇵🇹Creixomil, Portugal
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
The Lipid Clinic (Oslo University Hospital)
🇳🇴Oslo, Norway
Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz
🇵🇹Carnaxide, Portugal
Diabetes/Lipid Management & Research Center
🇺🇸Huntington Beach, California, United States
University of California, San Francisco (UCSF) - Medical Center
🇺🇸San Francisco, California, United States
Excel Medical Clinical Trials, LLC
🇺🇸Boca Raton, Florida, United States
NorthShore University Health System
🇺🇸Evanston, Illinois, United States
Advocate Health and Hospitals Corporation - Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Ascension St. Vincent Cardiovascular Research Institute
🇺🇸Indianapolis, Indiana, United States
University of Kansas Medical Center (KUMC)
🇺🇸Kansas City, Kansas, United States
University of Michigan- Endocrinology & Metabolism
🇺🇸Ann Arbor, Michigan, United States
New York University (NYU) Langone Medical Center
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Moses H. Cone Memorial Hospital
🇺🇸Greensboro, North Carolina, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
York Clinical Research LLC
🇺🇸Norfolk, Virginia, United States
West Virginia University Heart and Vascular Institute
🇺🇸Morgantown, West Virginia, United States
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
Nathalie Saint-Pierre
🇨🇦Montréal, Quebec, Canada
Clinique des Maladies Lipidiques de Quebec Inc.
🇨🇦Québec, Quebec, Canada
Institute de Recherches Cliniques de Montreal
🇨🇦Montréal, Canada
Hôpital Louis Pradel - HCL
🇫🇷Bron, France
CHU Dijon - Bocage
🇫🇷Dijon, France
Assistance Publique - Hopitaux de Marseille
🇫🇷Marseille, France
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Azienda Ospedaliero Universitaria Policlinico Umberto I
🇮🇹Roma, Italy
Academic Medical Center - Department of Vascular Medicine
🇳🇱Amsterdam, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz
🇵🇹Lisboa, Portugal
Metabolicke centrum MUDr Katariny Raslovej s. r. o.
🇸🇰Bratislava, Slovakia
Hospital Abente y Lago
🇪🇸A Coruña, Spain
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Fundacio Pere Virgili
🇪🇸Tarragona, Spain
Sahlgrenska University Hospital
🇸🇪Göteborg, Sweden
Karolinska University Hospital
🇸🇪Solna, Sweden
The Royal Free Hospital
🇬🇧London, United Kingdom
St. Thomas' Hospital
🇬🇧London, United Kingdom
Manchester University NHS Foundation Trust (MFT)
🇬🇧Manchester, United Kingdom
Sandwell General Hospital
🇬🇧West Bromwich, United Kingdom