A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy of Olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

Detailed Description
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This is a multi-center, double-blind, Phase 3 study in up to 60 patients with FCS. Participants will be randomized in a 2:1 ratio to receive Olezarsen or matching placebo in a 53-week treatment period. The length of participation in the study is approximately 74 weeks, which includes an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period. Following the treatment period, eligible patients may have the option of enrolling in an open label extension study.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)

Conditions
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Familial Chylomicronemia Syndrome

Intervention / Treatment
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* Drug: Olezarsen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: A diagnosis of genetically confirmed Familial Chylomicronemia Syndrome (type 1 Hyperlipoproteinemia) Fasting TG ≥ 880 mg/dL (10 millimoles per liter (mmol/L) at Screening History of pancreatitis. Patients without a documented history of pancreatitis are also eligible but their enrollment will be capped at 35% Stable doses of statins, omega-3 fatty acids, fibrates, or other lipid-lowering medications are allowed Key Exclusion Criteria: Acute coronary syndrome within 6 months of Screening Major surgery within 3 months of Screening Have any other conditions, which, in the opinion of the Investigator would make the participant unsuitable for inclusion, or could interfere with participating in or completing 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olezarsen<br>Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49. | Drug: Olezarsen<br>* Olezarsen will be administered by SC injection.<br>* Other names: AKCEA-APOCIII-LRx;|
| Placebo Comparator: Placebo<br>Olezarsen-matching placebo will be administered once every 4 weeks by SC injection from Week 1 through Week 49. | Drug: Placebo<br>* Olezarsen-matching placebo will be administered by SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Fasting TG at 6 Months (average of Weeks 23, 25, and 27) compared to placebo |  | Baseline and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Fasting TG at 12 months (average of Weeks 51 and 53) compared to placebo |  | Baseline and Month 12 | 
| Change from Baseline in the Proportion of Participants who Achieve ≥ 40% Reduction in Fasting TG at 6 Months Compared to Placebo |  | Baseline and Month 6 | 
| Percent Change form Baseline in Fasting Apolipoprotein B-48 (apoB-48) at 6 Months Compared to Placebo |  | At Month 6 | 
| Proportion of Participants who Achieve Fasting TG ≤ 750 mg/dL at 6 Months compared to placebo |  | At Month 6 | 
| Adjudicated Acute Pancreatitis Event Rate during the Treatment Period Compared to Placebo, in Participants with ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years prior to Enrollment |  | Week 1 through Week 53 | 
| Adjudicated Acute Pancreatitis Event Rate during the Treatment Period Compared to Placebo |  | Week 1 through Week 53 | 
| Change from Baseline in the Proportion of Participants who Achieve ≥ 70% Reduction in Fasting TG at 6 Months Compared to Placebo |  | Baseline and Month 6 | 
| Proportion of Participants who Achieve Fasting TG ≤ 500 mg/dL at 6 Months Compared to Placebo |  | At Month 6 | 

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