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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

Primary Purpose

Familial Chylomicronemia Syndrome

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Olezarsen
Sponsored by
Ionis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Familial Chylomicronemia Syndrome focused on measuring FCS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Diabetes/Lipid Management & Research Center
  • Excel Medical Clinical Trials, LLC
  • University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND)
  • University of Rochester School of Medicine
  • Centre for Heart Lung Innovation
  • ARC Biosystems, Clinical Assessment Unit (CAU)
  • St. Boniface General Hospital
  • Ecogene-21
  • Clinique des Maladies Lipidiques de Quebec Inc.
  • Centre Hospitalier Universite de Sherbrooke (CHUS)
  • Karolinska University Hospital Huddinge

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Olezarsen

Arm Description

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 153 weeks.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Trough (Pre-Dose) Plasma Concentration of Olezarsen
Post-Treatment Plasma Concentration of Olezarsen
Change and Percent Change From Baseline in Fasting Triglycerides (TG)
Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III)
Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C
Change and Percent Change From Baseline in Fasting Chylomicron-TG
Change and Percent Change From Baseline in Fasting Total Cholesterol (TC)
Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C
Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C
Change and Percent Change From Baseline in Fasting Apoprotein B (apoB)
Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48)
Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C
Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1)
Event Rate of Acute Pancreatitis

Full Information

First Posted
November 20, 2021
Last Updated
August 7, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05185843
Brief Title
A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 25, 2022 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Familial Chylomicronemia Syndrome
Keywords
FCS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Olezarsen
Arm Type
Experimental
Arm Description
Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 153 weeks.
Intervention Type
Drug
Intervention Name(s)
Olezarsen
Other Intervention Name(s)
ISIS 678354, AKCEA-APOCIII-LRx
Intervention Description
Olezarsen will be administered by SC injection.
Primary Outcome Measure Information:
Title
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
Title
Proportion of Participants With Major or Clinically Relevant Non-major Bleeding Events
Time Frame
Baseline to Week 157
Title
Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by >30% or >50%
Time Frame
Baseline to Week 157
Title
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
Title
Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >5 x Upper Limit of Normal (ULN)
Time Frame
Baseline to Week 157
Title
Proportion of Participants With ALT or AST >3 x ULN and Total Bilirubin > 2 x ULN
Time Frame
Baseline to Week 157
Title
Proportion of Participants With Total Bilirubin >2 mg/deciliter (dL)
Time Frame
Baseline to Week 157
Secondary Outcome Measure Information:
Title
Trough (Pre-Dose) Plasma Concentration of Olezarsen
Time Frame
Up to 157 weeks
Title
Post-Treatment Plasma Concentration of Olezarsen
Time Frame
Up to 170 weeks
Title
Change and Percent Change From Baseline in Fasting Triglycerides (TG)
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III)
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Chylomicron-TG
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Total Cholesterol (TC)
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Apoprotein B (apoB)
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48)
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C
Time Frame
Baseline to Week 157
Title
Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1)
Time Frame
Baseline to Week 157
Title
Event Rate of Acute Pancreatitis
Time Frame
Up to 157 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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 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: 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 Concomitant medication/procedure restrictions: Systemic corticosteroids or anabolic steroids within 6 weeks prior to Screening and during the study unless approved by the Sponsor Medical Monitor Plasma apheresis within 4 weeks prior to Screening or planned during the study
Facility Information:
Facility Name
Diabetes/Lipid Management & Research Center
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92648
Country
United States
Facility Name
Excel Medical Clinical Trials, LLC
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33434
Country
United States
Facility Name
University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND)
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-2800
Country
United States
Facility Name
University of Rochester School of Medicine
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Centre for Heart Lung Innovation
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
ARC Biosystems, Clinical Assessment Unit (CAU)
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2C7
Country
Canada
Facility Name
St. Boniface General Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2Ab
Country
Canada
Facility Name
Ecogene-21
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
Clinique des Maladies Lipidiques de Quebec Inc.
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1V 4W2
Country
Canada
Facility Name
Centre Hospitalier Universite de Sherbrooke (CHUS)
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Karolinska University Hospital Huddinge
City
Stockholm
ZIP/Postal Code
171 77
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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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