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

February 13, 2025 updated by: Ionis Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Approved

Approved

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Montréal, Canada, H2W 1R7
        • Institute de Recherches Cliniques de Montreal
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 7K9
        • Ecogene-21
      • Montréal, Quebec, Canada, H2W 1R7
        • Nathalie Saint-Pierre
      • Québec, Quebec, Canada, G1V 4W2
        • Clinique des Maladies Lipidiques de Quebec Inc.
  • France
      • Bron, France, 69677
        • Hôpital Louis Pradel - HCL
      • Dijon, France, 21000
        • CHU Dijon - Bocage
      • Marseille, France, 13385
        • Assistance Publique - Hopitaux de Marseille
  • Italy
      • Milano, Italy, 20162
        • ASST Grande Ospedale Metropolitano Niguarda
      • Napoli, Italy, 80131
        • Azienda Ospedaliera Universitaria Federico II
      • Palermo, Italy, 90127
        • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
      • Roma, Italy, 00161
        • Azienda Ospedaliero Universitaria Policlinico Umberto I
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Academic Medical Center - Department of Vascular Medicine
      • Rotterdam, Netherlands, 3015 GD
        • Erasmus MC
      • Utrecht, Netherlands, 3584 CX
        • Universitair Medisch Centrum Utrecht
  • Norway
      • Oslo, Norway, 0372
        • The Lipid Clinic (Oslo University Hospital)
  • Portugal
      • Carnaxide, Portugal, 2790-134
        • Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz
      • Creixomil, Portugal, 4835-044
        • Hospital da Senhora da Oliveira - Guimarães
      • Lisboa, Portugal, 1349-019
        • Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz
  • Slovakia
      • Bratislava, Slovakia, 83301
        • Metabolicke centrum MUDr Katariny Raslovej s. r. o.
  • Spain
      • A Coruña, Spain, 15001
        • Hospital Abente y Lago
      • Barcelona, Spain, 08036
        • Hospital Clinic Barcelona
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Tarragona, Spain, 43204
        • Fundacio Pere Virgili
  • Sweden
      • Göteborg, Sweden, 413 45
        • Sahlgrenska University Hospital
      • Solna, Sweden, 171 76
        • Karolinska University Hospital
  • United Kingdom
      • London, United Kingdom, SE1 7EH
        • St. Thomas' Hospital
      • London, United Kingdom, NW3 2QG
        • The Royal Free Hospital
      • Manchester, United Kingdom, MI39WL
        • Manchester University NHS Foundation Trust (MFT)
      • West Bromwich, United Kingdom, B71 4HJ
        • Sandwell General Hospital
  • United States
    • California
      • Huntington Beach, California, United States, 92648
        • Diabetes/Lipid Management & Research Center
      • San Francisco, California, United States, 94143
        • University of California, San Francisco (UCSF) - Medical Center
    • Florida
      • Boca Raton, Florida, United States, 33434
        • Excel Medical Clinical Trials, LLC
    • Illinois
      • Evanston, Illinois, United States, 60201
        • Northshore University Health System
      • Park Ridge, Illinois, United States, 60068
        • Advocate Health and Hospitals Corporation - Lutheran General Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46290
        • Ascension St. Vincent Cardiovascular Research Institute
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center (KUMC)
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan- Endocrinology & Metabolism
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10016
        • New York University (NYU) Langone Medical Center
    • North Carolina
      • Greensboro, North Carolina, United States, 27401
        • Moses H. Cone Memorial Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Virginia
      • Norfolk, Virginia, United States, 23510
        • York Clinical Research LLC
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Heart and Vascular Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: 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.
Drug: Placebo
Olezarsen-matching placebo was administered by SC injection.
Experimental: Olezarsen 50 mg
Participants received olezarsen, 50 milligrams (mg), once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Drug: Olezarsen
Olezarsen was administered by SC injection.
Other Names:
  • ISIS 678354
  • AKCEA-APOCIII-LRx
Experimental: Olezarsen 80 mg
Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period.
Drug: Olezarsen
Olezarsen was administered by SC injection.
Other Names:
  • ISIS 678354
  • AKCEA-APOCIII-LRx

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percent Change From Baseline in Fasting TG at Month 6
Time Frame: Baseline, Month 6
Baseline, Month 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Fasting TG at Month 12
Time Frame: Baseline, Month 12
Baseline, Month 12
Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12
Time Frame: Baseline, Months 6 and 12
Baseline, Months 6 and 12
Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6
Time Frame: Month 6
Percentages are rounded off to the nearest single decimal place.
Month 6
Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12
Time Frame: Baseline, 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
Time Frame: Baseline, 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
Time Frame: 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.
During the treatment period Week 1 through Week 53
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53)
Time Frame: 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.
During the treatment period Week 1 through Week 53
Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis
Time Frame: 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.
Week 13 through Week 53
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53
Time Frame: 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.
Week 13 through Week 53
Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6
Time Frame: Month 6
Percentages are rounded off to the nearest single decimal place.
Month 6
Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6
Time Frame: Month 6
Percentages are rounded off to the nearest single decimal place.
Month 6
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment
Time Frame: 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.
During the treatment period Week 1 through Week 53
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
Time Frame: 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.
Week 13 to Week 53
Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6
Time Frame: Month 6
Percentages are rounded off to the nearest single decimal place.
Month 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ionis Pharmaceuticals, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Akcea Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 18, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 14, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 17, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 23, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 29, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ISIS 678354-CS3
  • 2020-002536-67 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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/.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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