NCT04568434

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
66

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 2020

Typical duration for phase_3

Geographic Reach
11 countries

47 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 23, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

September 29, 2020

Completed
2 months until next milestone

Study Start

First participant enrolled

November 18, 2020

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 14, 2023

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 17, 2023

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

March 6, 2025

Completed
Last Updated

March 6, 2025

Status Verified

February 1, 2025

Enrollment Period

2.7 years

First QC Date

September 23, 2020

Results QC Date

February 13, 2025

Last Update Submit

February 13, 2025

Conditions

Keywords

FCS

Outcome Measures

Primary Outcomes (1)

  • Percent Change From Baseline in Fasting TG at Month 6

    Baseline, Month 6

Secondary Outcomes (14)

  • 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

  • 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

  • +9 more secondary outcomes

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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 50 mg

EXPERIMENTAL

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 80 mg

EXPERIMENTAL

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

Interventions

Olezarsen was administered by SC injection.

Also known as: ISIS 678354, AKCEA-APOCIII-LRx
Olezarsen 50 mgOlezarsen 80 mg

Olezarsen-matching placebo was administered by SC injection.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Acute coronary syndrome within 6 months of Screening
  • Major surgery within 3 months of Screening

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (47)

Diabetes/Lipid Management & Research Center

Huntington Beach, California, 92648, United States

Location

University of California, San Francisco (UCSF) - Medical Center

San Francisco, California, 94143, United States

Location

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, 33434, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Advocate Health and Hospitals Corporation - Lutheran General Hospital

Park Ridge, Illinois, 60068, United States

Location

Ascension St. Vincent Cardiovascular Research Institute

Indianapolis, Indiana, 46290, United States

Location

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, 66160, United States

Location

University of Michigan- Endocrinology & Metabolism

Ann Arbor, Michigan, 48105, United States

Location

New York University (NYU) Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Moses H. Cone Memorial Hospital

Greensboro, North Carolina, 27401, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

York Clinical Research LLC

Norfolk, Virginia, 23510, United States

Location

West Virginia University Heart and Vascular Institute

Morgantown, West Virginia, 26506, United States

Location

Ecogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Nathalie Saint-Pierre

Montreal, Quebec, H2W 1R7, Canada

Location

Clinique des Maladies Lipidiques de Quebec Inc.

Québec, Quebec, G1V 4W2, Canada

Location

Institute de Recherches Cliniques de Montreal

Montreal, H2W 1R7, Canada

Location

Hôpital Louis Pradel - HCL

Bron, 69677, France

Location

CHU Dijon - Bocage

Dijon, 21000, France

Location

Assistance Publique - Hopitaux de Marseille

Marseille, 13385, France

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90127, Italy

Location

Azienda Ospedaliero Universitaria Policlinico Umberto I

Roma, 00161, Italy

Location

Academic Medical Center - Department of Vascular Medicine

Amsterdam, 1105 AZ, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

The Lipid Clinic (Oslo University Hospital)

Oslo, 0372, Norway

Location

Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz

Carnaxide, 2790-134, Portugal

Location

Hospital da Senhora da Oliveira - Guimaraes

Creixomil, 4835-044, Portugal

Location

Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz

Lisbon, 1349-019, Portugal

Location

Metabolicke centrum MUDr Katariny Raslovej s. r. o.

Bratislava, 83301, Slovakia

Location

Hospital Abente y Lago

A Coruña, 15001, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Fundacio Pere Virgili

Tarragona, 43204, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Karolinska University Hospital

Solna, 171 76, Sweden

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

St. Thomas' Hospital

London, SE1 7EH, United Kingdom

Location

Manchester University NHS Foundation Trust (MFT)

Manchester, MI39WL, United Kingdom

Location

Sandwell General Hospital

West Bromwich, B71 4HJ, United Kingdom

Location

Related Publications (2)

  • 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.

  • Sikora Kessler A, Vera-Llonch M, Karwatowska-Prokopczuk E, Alexander VJ, Ann Q, Mejia Herrera C, Paparrodopoulos S, Xia S, Stroes ESG, Baum SJ, Tsimikas S; Balance Investigators. Olezarsen reduces all-cause health services utilization and improves the treatment experience of patients with familial chylomicronemia syndrome. J Clin Lipidol. 2025 Dec 19:S1933-2874(25)00547-1. doi: 10.1016/j.jacl.2025.12.018. Online ahead of print.

MeSH Terms

Conditions

Familial hyperchylomicronemia syndrome

Interventions

olezarsen

Results Point of Contact

Title
Ionis Pharmaceuticals, Inc.
Organization
Ionis Pharmaceuticals, Inc.

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

September 23, 2020

First Posted

September 29, 2020

Study Start

November 18, 2020

Primary Completion

July 14, 2023

Study Completion

October 17, 2023

Last Updated

March 6, 2025

Results First Posted

March 6, 2025

Record last verified: 2025-02

Data Sharing

IPD Sharing
Will share

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/.

More information

Locations