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

An Open-Label Extension Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)

The purpose of this study is to evaluate the effect of olezarsen (formerly known as AKCEA-APOCIII-LRx) on the percent change in fasting triglycerides (TG) from baseline.

Study Overview

• Status: Active, not recruiting
• Conditions: Familial Chylomicronemia Syndrome
• Intervention / Treatment: Drug: Olezarsen

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Ecogene-21
    • Montreal, Quebec, Canada, H2W 1R7
      • Institute de Recherches Cliniques de Montreal
    • Montréal, Quebec, Canada, H2W 1R7
      • Nathalie Saint-Pierre
    • Québec, Quebec, Canada, G1V 4W2
      • Clinique des Maladies Lipidiques de Quebec Inc.
• France
  • Bron, France, 69677
    • Groupement Hospitalier Est- Pharmacie Secteur Essais Clinique
  • Le Kremlin-Bicêtre, France, 94270
    • Hôpital Bicêtre
  • Marseille, France, 05 13385
    • Pharmacie Hopital de la Conception
• Italy
  • Napoli, Italy, 80131
    • Via Sergio Pansini 5
  • Palermo, Italy, 90127
    • UOC di Farmacia AOUP PAOLO GIACCONE
  • Rome, Italy, 00161
    • Azienda Ospedaliero Universitaria Policlinico Umberto I
• Netherlands
  • Noor-Holland
    • Amsterdam, Noor-Holland, Netherlands, 1105 AZ
      • Academisch Medisch Centrum Goederenontvangst Apotheek t.a.v. Kenniscentrum
• Norway
  • Oslo, Norway, 0372
    • Oslo Hospital Pharmacy Rikshospitalet
• Portugal
  • Creixomil, Portugal, 4835-044
    • Hospital da Senhora da Oliveira Guimarães
  • Lisboa, Portugal, 1340-019
    • Dra Margarida Falcao Centro Hospitalar Lisboa Ocidental Hospital Egas Moniz
• Slovakia
  • Bratislava, Slovakia, 83101
    • Metabolicke centrum MU
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic Barcelona C/ Villarroel
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• Sweden
  • Malmö, Sweden, 211 24
    • Apokteket AB
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
• United States
  • California
    • Huntington Beach, California, United States, 92648
      • Diabetes/Lipid Management & Research Center
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Department of Pharmacy
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (KUMC)
  • New York
    • New York, New York, United States, 10016
      • CTSI Investigational Pharmacy
    • New York, New York, United States, 10032
      • Milstein Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • IDS Central

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.; Other Names: ISIS 678354; AKCEA -APOCIII-LRx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Fasting TG at 6 Months (Average of Weeks 23, 25, and 27) Compared to Baseline	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Achieve ≥ 40% Reduction in Fasting TG From Baseline at 6 Months	At 6 months
Percent Change From Baseline in Fasting Apolipoprotein 48 (apoB48) at 6 Months	At 6 months
Percentage of Participants Who Achieve ≥ 70% Reduction in Fasting TG From Baseline at 6 Months	At 6 months
Percentage of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 6 Months	At 6 months
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)	Baseline and 36 months
Percentage of Participants Who Achieve ≥ 40% Reduction in Fasting TG From Baseline at 12, 24, 36 Months	At 12, 24, 36 months
Percent Change From Baseline in Fasting apoB48 at 12, 24, 36 Months	At 12, 24, 36 months
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period	Week 1 through Weeks 53, 105, or 157
Percentage of Participants Who Achieve ≥ 70% Reduction in Fasting TG From Baseline at 12, 24, 36 Months	At 12, 24, 36 months
Percentage of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 12, 24, 36 Months	At 12, 24, 36 months
Percent Change in Fasting apoC-III from Baseline at Month 6	Baseline and 6 months
Percent Change in Fasting apoC-III from Month 12, 24, 36	At 12, 24, 36 months
Percent Change in Fasting non-HDL-C from Baseline at Month 6	Baseline and 6 months
Percent Change in Fasting non-HDL-C from Months 12, 24, 36	At 12, 24, 36 months
Percentage of Participants Who Achieve Fasting TG ≤ 880 milligrams per deciliter (mg/dL) at 6 Months	At 6 months
Percentage of Participants Who Achieve Fasting TG ≤ 880 mg/dL at 12, 24, 36 months	At 12, 24, 36 months
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	Week 1 through Week 157
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	Week 1 through Weeks 53, 105, or 157

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: FCS
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Syndrome; Hyperlipoproteinemia Type I
• Other Study ID Numbers: ISIS 678354-CS13; 2021-003280-95 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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