A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)

Familial Chylomicronemia Syndrome Clinical Trial

— BALANCE  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04568434
• Other study ID #: ISIS 678354-CS3
• Secondary ID: 2020-002536-67
• Status: Completed
• Phase: Phase 3
• Start date: November 16, 2020
• Est. completion date: October 17, 2023

Study information

• Verified date: March 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, double-blind, Phase 3 study in up to 60 patients with FCS. Participants will be 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 is approximately 74 weeks, which includes 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 may have the option of enrolling in an open label extension study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: October 17, 2023
• Est. primary completion date: July 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Familial Chylomicronemia Syndrome
• Hyperlipoproteinemia Type I
• Syndrome

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
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Institute de Recherches Cliniques de Montreal	Montréal
Canada	Nathalie Saint-Pierre	Montréal	Quebec
Canada	Clinique des Maladies Lipidiques de Quebec Inc.	Québec	Quebec
France	Hôpital Louis Pradel - HCL	Bron
France	CHU Dijon - Bocage	Dijon
France	Assistance Publique - Hopitaux de Marseille	Marseille
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Székesfehérvár
Israel	Ziv Medical Center	Safed
Italy	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
Netherlands	Academic Medical Center - Department of Vascular Medicine	Amsterdam
Netherlands	Erasmus MC	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Norway	The Lipid Clinic (Oslo University Hospital)	Oslo
Portugal	Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz	Carnaxide
Portugal	Hospital da Senhora da Oliveira - Guimaraes	Creixomil
Portugal	Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz	Lisboa
Slovakia	Metabolicke centrum MUDr Katariny Raslovej s. r. o.	Bratislava
Spain	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
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Karolinska University Hospital	Solna
United Kingdom	St. Thomas' Hospital	London
United Kingdom	The Royal Free Hospital	London
United Kingdom	Manchester University NHS Foundation Trust (MFT)	Manchester
United Kingdom	Sandwell General Hospital	West Bromwich
United States	University of Michigan- Endocrinology & Metabolism	Ann Arbor	Michigan
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida
United States	University of Texas Southwestern	Dallas	Texas
United States	NorthShore University Health System	Evanston	Illinois
United States	Moses H. Cone Memorial Hospital	Greensboro	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Diabetes/Lipid Management & Research Center	Huntington Beach	California
United States	Ascension St. Vincent Cardiovascular Research Institute	Indianapolis	Indiana
United States	University of Kansas Medical Center (KUMC)	Kansas City	Kansas
United States	West Virginia University Heart and Vascular Institute	Morgantown	West Virginia
United States	Vanderbilt University	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	New York University (NYU) Langone Medical Center	New York	New York
United States	York Clinical Research LLC	Norfolk	Virginia
United States	Advocate Health and Hospitals Corporation - Lutheran General Hospital	Park Ridge	Illinois
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of California, San Francisco (UCSF) - Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Hungary,  Israel,  Italy,  Netherlands,  Norway,  Portugal,  Slovakia,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from Baseline in Fasting TG at 6 Months (average of Weeks 23, 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	Percent Change in Fasting apoC-III from Baseline at 6 Months and 12 Months Compared to Placebo		Baseline, Month 6 and Month 12
Secondary	Change from Baseline in the Proportion of Participants who Achieve = 40% Reduction in Fasting TG at 6 Months Compared to Placebo		Baseline and Month 6
Secondary	Percent Change from Baseline in Fasting Apolipoprotein B-48 (apoB-48) at 6 Months and 12 Months Compared to Placebo		Baseline, Month 6 and Month 12
Secondary	Percent Change in Fasting non-HDL-C from Baseline at 6 Months and 12 Months Compared to Placebo		Baseline, Month 6 and Month 12
Secondary	Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo in Patients with a History of Pancreatitis within 10 Years Prior to Screening		Week 1 through Week 53 and Week 13 through Week 53
Secondary	Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo		Week 1 through Week 53 and Week 13 through Week 53
Secondary	Change from Baseline in the Proportion of Participants Who Achieve = 70% Reduction in Fasting TG at 6 Months Compared to Placebo		Baseline and Month 6
Secondary	Proportion of Participants Who Achieve Fasting TG = 880 mg/dL at 6 Months Compared to Placebo		Week 1 through Week 53
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 and Week 13 through Week 53
Secondary	Proportion of Participants Who Achieve Fasting TG = 500 mg/dL at 6 Months Compared to Placebo		At Month 6