Clinical trial NCT04568434: A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Familial Chylomicronemia Syndrome
Keywords: FCS
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-29
Enrollment: 66
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 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).

Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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

Primary outcomes:
measure: Percent Change From Baseline in Fasting TG at Month 6
timeFrame: Baseline, Month 6
Secondary outcomes:
measure: Percent Change From Baseline in Fasting TG at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12
timeFrame: Baseline, Months 6 and 12
measure: Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6
timeFrame: Month 6
measure: Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12
timeFrame: Baseline, Months 6 and 12
measure: 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
timeFrame: During the treatment period Week 1 through Week 53
measure: Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53)
timeFrame: During the treatment period Week 1 through Week 53
measure: Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis
timeFrame: Week 13 through Week 53
measure: Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53
timeFrame: Week 13 through Week 53
measure: Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6
timeFrame: Month 6
measure: Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6
timeFrame: Month 6
measure: Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment
timeFrame: During the treatment period Week 1 through Week 53
measure: 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
timeFrame: Week 13 to Week 53
measure: Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6
timeFrame: Month 6
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Diabetes/Lipid Management & Research Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF) - Medical Center
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Health and Hospitals Corporation - Lutheran General Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent Cardiovascular Research Institute
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan- Endocrinology & Metabolism
state: Michigan
city: New York
country: United States
facility: New York University (NYU) Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Greensboro
country: United States
facility: Moses H. Cone Memorial Hospital
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Norfolk
country: United States
facility: York Clinical Research LLC
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Heart and Vascular Institute
state: West Virginia
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Montréal
country: Canada
facility: Nathalie Saint-Pierre
state: Quebec
city: Québec
country: Canada
facility: Clinique des Maladies Lipidiques de Quebec Inc.
state: Quebec
city: Montréal
country: Canada
facility: Institute de Recherches Cliniques de Montreal
city: Bron
country: France
facility: Hôpital Louis Pradel - HCL
city: Dijon
country: France
facility: CHU Dijon - Bocage
city: Marseille
country: France
facility: Assistance Publique - Hopitaux de Marseille
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Umberto I
city: Amsterdam
country: Netherlands
facility: Academic Medical Center - Department of Vascular Medicine
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Oslo
country: Norway
facility: The Lipid Clinic (Oslo University Hospital)
city: Carnaxide
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz
city: Creixomil
country: Portugal
facility: Hospital da Senhora da Oliveira - Guimaraes
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz
city: Bratislava
country: Slovakia
facility: Metabolicke centrum MUDr Katariny Raslovej s. r. o.
city: A Coruña
country: Spain
facility: Hospital Abente y Lago
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Tarragona
country: Spain
facility: Fundacio Pere Virgili
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Solna
country: Sweden
facility: Karolinska University Hospital
city: London
country: United Kingdom
facility: The Royal Free Hospital
city: London
country: United Kingdom
facility: St. Thomas' Hospital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust (MFT)
city: West Bromwich
country: United Kingdom
facility: Sandwell General Hospital
Study officials:
References:
citation: Stroes ESG, Alexander VJ, Karwatowska-Prokopczuk E, Hegele RA, Arca M, Ballantyne CM, Soran H, Prohaska TA, Xia S, Ginsberg HN, Witztum JL, Tsimikas S; Balance Investigators. Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome. N Engl J Med. 2024 May 16;390(19):1781-1792. doi: 10.1056/NEJMoa2400201. Epub 2024 Apr 7.