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A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen

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ClinicalTrials.gov Identifier: NCT05185843
Recruitment Status : Recruiting
First Posted : January 11, 2022
Last Update Posted : June 6, 2023
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Study Description
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Brief Summary:
The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of olezarsen (formerly known as AKCEA -APOCIII-LRX) in participants with FCS previously treated with volanesorsen.

Condition or disease Intervention/treatment Phase
Familial Chylomicronemia Syndrome Drug: Olezarsen Phase 3

Detailed Description:

This is a Phase 3, multi-center, open-label safety study of up to 30 participants with FCS, previously treated with volanesorsen. The study consists of 3 periods: 1) Screening Period: Week -8 to Week -1 (up to 8 weeks); 2) Treatment Period up to Week 157; and 3) Post-Treatment Follow-up Period: Week 158 to Week 170 (12 weeks). Participants enrolled will receive olezarsen every 4 weeks during the 157-week Treatment Period.

This study was extended to allow participants to receive olezarsen for an additional 104 weeks following the initial 53-week treatment period.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Safety Study of AKCEA-APOCIII-LRX Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen (ISIS 304801)
Actual Study Start Date : February 25, 2022
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : June 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Family Issues

Arms and Interventions
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Arm Intervention/treatment
Experimental: Olezarsen
Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 153 weeks.
 Drug: Olezarsen
Olezarsen will be administered by SC injection.
Other Names:
  • ISIS 678354
  • AKCEA-APOCIII-LRx


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of Participants With Decrease in Platelet Count by >30% or >50%, or With Platelet Count Value <50,000/cubic millimeter (mm^3) [ Time Frame: Baseline to Week 157 ]
  2. Proportion of Participants With Major or Clinically Relevant Non-major Bleeding Events [ Time Frame: Baseline to Week 157 ]
  3. Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by >30% or >50% [ Time Frame: Baseline to Week 157 ]
  4. Proportion of Participants With Urine Protein/Creatinine Ratio (UPCR) ≥1000 milligram (mg)/gram (g) or with Urine/Albumin Creatinine Ratio (UACR) ≥500 mg/g [ Time Frame: Baseline to Week 157 ]
  5. Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >5 x Upper Limit of Normal (ULN) [ Time Frame: Baseline to Week 157 ]
  6. Proportion of Participants With ALT or AST >3 x ULN and Total Bilirubin > 2 x ULN [ Time Frame: Baseline to Week 157 ]
  7. Proportion of Participants With Total Bilirubin >2 mg/deciliter (dL) [ Time Frame: Baseline to Week 157 ]

Secondary Outcome Measures :
  1. Trough (Pre-Dose) Plasma Concentration of Olezarsen [ Time Frame: Up to 157 weeks ]
  2. Post-Treatment Plasma Concentration of Olezarsen [ Time Frame: Up to 170 weeks ]
  3. Change and Percent Change From Baseline in Fasting Triglycerides (TG) [ Time Frame: Baseline to Week 157 ]
  4. Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III) [ Time Frame: Baseline to Week 157 ]
  5. Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C [ Time Frame: Baseline to Week 157 ]
  6. Change and Percent Change From Baseline in Fasting Chylomicron-TG [ Time Frame: Baseline to Week 157 ]
  7. Change and Percent Change From Baseline in Fasting Total Cholesterol (TC) [ Time Frame: Baseline to Week 157 ]
  8. Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C [ Time Frame: Baseline to Week 157 ]
  9. Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C [ Time Frame: Baseline to Week 157 ]
  10. Change and Percent Change From Baseline in Fasting Apoprotein B (apoB) [ Time Frame: Baseline to Week 157 ]
  11. Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48) [ Time Frame: Baseline to Week 157 ]
  12. Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C [ Time Frame: Baseline to Week 157 ]
  13. Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1) [ Time Frame: Baseline to Week 157 ]
  14. Event Rate of Acute Pancreatitis [ Time Frame: Up to 157 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Participants with FCS (clinical or genetic diagnosis) currently on or previously treated with volanesorsen (ISIS 304801)

    o Study participants in countries where Waylivra® is commercially approved and available for participants should not be deprived of the treatment option with Waylivra®. Participation in this study for such participants will only be allowed when Waylivra® was discontinued due to AEs

  2. The following concomitant medications will be allowed if dosing regimen is expected to remain constant through the end of the study (occasional or intermittent use of over-the-counter (OTC) medications will be allowed at Investigator's discretion):

    • Statins, omega-3 fatty acids (prescription and OTC), fibrates, or other lipid-lowering medications. Participants taking OTC omega-3 fatty acids should make every effort to remain on the same brand through the end of the study
    • Antidiabetic medications
    • Oral anticoagulants (e.g., dabigatran, rivaroxaban, or apixaban, and warfarin with regular clinical monitoring)
    • Tamoxifen, estrogens or progestins

Exclusion Criteria:

  1. Treatment with another investigational drug (non-oligonucleotide), biological agent, or device within 4 weeks of Screening, or 5 half-lives of investigational agent, whichever is longer

  2. Concomitant medication/procedure restrictions:

    1. Systemic corticosteroids or anabolic steroids within 6 weeks prior to Screening and during the study unless approved by the Sponsor Medical Monitor
    2. Plasma apheresis within 4 weeks prior to Screening or planned during the study
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05185843


Contacts
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Contact: Ionis Pharmaceuticals (844) 583-0450 ionisNCT05130450study@clinicaltrialmedia.com

Locations
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United States, California
Diabetes/Lipid Management & Research Center Recruiting
Huntington Beach, California, United States, 92648
United States, Florida
Excel Medical Clinical Trials, LLC Recruiting
Boca Raton, Florida, United States, 33434
United States, Michigan
University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND) Recruiting
Ann Arbor, Michigan, United States, 48109-2800
United States, New York
University of Rochester School of Medicine Recruiting
Rochester, New York, United States, 14642
Canada, British Columbia
Centre for Heart Lung Innovation Recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
ARC Biosystems, Clinical Assessment Unit (CAU) Recruiting
Vancouver, British Columbia, Canada, V6Z 2C7
Canada, Manitoba
St. Boniface General Hospital Recruiting
Winnipeg, Manitoba, Canada, R2H 2Ab
Canada, Quebec
Ecogene-21 Recruiting
Chicoutimi, Quebec, Canada, G7H 7K9
Clinique des Maladies Lipidiques de Quebec Inc. Recruiting
Québec, Quebec, Canada, G1V 4W2
Centre Hospitalier Universite de Sherbrooke (CHUS) Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Sweden
Karolinska University Hospital Huddinge Recruiting
Stockholm, Sweden, 171 77
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
More Information
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05185843    
Other Study ID Numbers: ISIS 678354-CS7
2021-003635-29 ( EudraCT Number )
First Posted: January 11, 2022    Key Record Dates
Last Update Posted: June 6, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ionis Pharmaceuticals, Inc.:
FCS
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type I
Syndrome
Disease
Pathologic Processes
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
 Genetic Diseases, Inborn
Hyperlipoproteinemias
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases