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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-Label Safety Study of AKCEA-APOCIII-LRX Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen (ISIS 304801)

Conditions
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Familial Chylomicronemia Syndrome

Intervention / Treatment
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* Drug: Olezarsen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olezarsen<br>Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 153 weeks. | Drug: Olezarsen<br>* Olezarsen will be administered by SC injection.<br>* Other names: AKCEA-APOCIII-LRx;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough (Pre-Dose) Plasma Concentration of Olezarsen |  | Up to 157 weeks | 
| Post-Treatment Plasma Concentration of Olezarsen |  | Up to 170 weeks | 
| Change and Percent Change From Baseline in Fasting Triglycerides (TG) |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III) |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Chylomicron-TG |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Total Cholesterol (TC) |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Apoprotein B (apoB) |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48) |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C |  | Baseline to Week 157 | 
| Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1) |  | Baseline to Week 157 | 
| Event Rate of Acute Pancreatitis |  | Up to 157 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FCS