A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified November 2025 by Ionis Pharmaceuticals, Inc.
Sponsor
Ionis Pharmaceuticals, Inc.
Information Provided by (Responsible Party)
Ionis Pharmaceuticals, Inc.
Clinicaltrials.gov Identifier
NCT05130450
Other Study ID Numbers:
ISIS 678354-CS13
First Submitted
November 10, 2021
First Posted
November 22, 2021
Last Update Posted
December 11, 2025
Last Verified
November 2025

ClinicalTrials.gov processed this data on December 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

This is a multi-center, open-label extension (OLE) study of up to 60 participants with FCS rolling-over from Study ISIS 678354-CS3 (NCT04568434). Participants will receive olezarsen during a 157-week treatment period, followed by a 13-week post-treatment follow-up period. The length of participation in this study is approximately 201 weeks, which includes an up to 31-day qualification period, a 157-week treatment period, and a 13-week post-treatment evaluation period.

Treatment has been extended to obtain additional safety assessments and efficacy data and to provide patients with continued access to ISIS 678354 until the drug may be available commercially.

Condition or DiseaseIntervention/Treatment
Familial Chylomicronemia Syndrome
Drug: Olezarsen

Study Design

Study TypeInterventional
Actual Enrollment60 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleAn Open-Label Extension Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
Study Start DateNovember 17, 2021
Actual Primary Completion Date1yr 8mos from now
Actual Study Completion Date1yr 8mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Olezarsen
Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 153.
Drug: Olezarsen
Olezarsen will be administered by SC injection.

Outcome Measures

Primary Outcome Measures
  1. Percent Change From Baseline in Fasting TG at 6 Months (Average of Weeks 23, 25, and 27) Compared to Baseline
Secondary Outcome Measures
  1. Percent Change From Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) at 24 Months (Average of Week 103 and Week 105) and 36 Months (Average of Week 155 and Week 157)
  2. Percentage of Participants Who Achieve ≥ 40% Reduction in Fasting TG From Baseline at 6 Months
  3. Percentage of Participants Who Achieve ≥ 40% Reduction in Fasting TG From Baseline at 12, 24, 36 Months
  4. Percent Change in Fasting apoC-III from Baseline at Month 6
  5. Percent Change in Fasting apoC-III from Month 12, 24, 36
  6. Percent Change From Baseline in Fasting Apolipoprotein 48 (apoB48) at 6 Months
  7. Percent Change From Baseline in Fasting apoB48 at 12, 24, 36 Months
  8. Percent Change in Fasting non-HDL-C from Baseline at Month 6
  9. Percent Change in Fasting non-HDL-C from Months 12, 24, 36
  10. Percentage of Participants Who Achieve Fasting TG ≤ 880 milligrams per deciliter (mg/dL) at 6 Months
  11. Percentage of Participants Who Achieve Fasting TG ≤ 880 mg/dL at 12, 24, 36 months
  12. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period in Participants With ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Treatment With Study Drug in the Index Study
  13. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period
  14. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period in Patients with a Prior History of Pancreatitis within 10 Years Prior to Screening in the Index Study
  15. Percentage of Participants Who Achieve ≥ 70% Reduction in Fasting TG From Baseline at 6 Months
  16. Percentage of Participants Who Achieve ≥ 70% Reduction in Fasting TG From Baseline at 12, 24, 36 Months
  17. Percentage of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 6 Months
  18. Percentage of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 12, 24, 36 Months

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
• Satisfactory completion of treatment with olezarsen in the index study (ISIS 678354-CS3, last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgement.
Exclusion Criteria
• Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the patient participating in or completing the study, including need for treatment with medications disallowed in the index study (ISIS 678354-CS3).

Contacts and Locations

Sponsors and CollaboratorsIonis Pharmaceuticals, Inc.
Locations
Diabetes/Lipid Management & Research Center | Huntington Beach California, United States, 92648Excel Medical Clinical Trials, LLC | Boca Raton Florida, United States, 33434Department of Pharmacy | Park Ridge Illinois, United States, 60068University of Kansas Medical Center (KUMC) | Kansas City Kansas, United States, 66160CTSI Investigational Pharmacy | New York New York, United States, 10016Milstein Hospital | New York New York, United States, 10032IDS Central | Philadelphia Pennsylvania, United States, 19104Ecogene-21 | Chicoutimi Quebec, Canada, G7H 7K9Institute de Recherches Cliniques de Montreal | Montreal Quebec, Canada, H2W 1R7Nathalie Saint-Pierre | Montreal Quebec, Canada, H2W 1R7Clinique des Maladies Lipidiques de Quebec Inc. | Québec Quebec, Canada, G1V 4W2Groupement Hospitalier Est- Pharmacie Secteur Essais Clinique | Bron , France, 69677Hôpital Bicêtre | Le Kremlin-Bicêtre , France, 94270Pharmacie Hopital de la Conception | Marseille , France, 05 13385Via Sergio Pansini 5 | Naples , Italy, 80131UOC di Farmacia AOUP PAOLO GIACCONE | Palermo , Italy, 90127Azienda Ospedaliero Universitaria Policlinico Umberto I | Rome , Italy, 00161Academisch Medisch Centrum Goederenontvangst Apotheek t.a.v. Kenniscentrum | Amsterdam Noor-Holland, Netherlands, 1105 AZOslo Hospital Pharmacy Rikshospitalet | Oslo , Norway, 0372Hospital da Senhora da Oliveira Guimaraes | Creixomil , Portugal, 4835-044Dra Margarida Falcao Centro Hospitalar Lisboa Ocidental Hospital Egas Moniz | Lisbon , Portugal, 1340-019Metabolicke centrum MU | Bratislava , Slovakia, 83101Hospital Clínic Barcelona C/ Villarroel | Barcelona , Spain, 08036Hospital Universitario 12 de Octubre | Madrid , Spain, 28041Hospital Universitario Virgen del Rocío | Seville , Spain, 41013Apokteket AB | Malmö , Sweden, 211 24Royal Manchester Children's Hospital | Manchester , United Kingdom, M13 9WL