Phase 2 Study of AKCEA-ANGPTL3-LRx (ISIS 703802) in Participants With Familial Chylomicronemia Syndrome (FCS)

Study Overview
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Brief Summary
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This is a single center, open-label study to evaluate the efficacy of AKCEA-ANGPTL3-LRx for reduction of triglyceride (TG) levels in participants with FCS.

Official Title
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A Phase 2 Open-Label Study to Assess the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of AKCEA-ANGPTL3-LRx (ISIS 703802) Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)

Conditions
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Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency, Hyperlipoproteinemia Type 1

Intervention / Treatment
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* Drug: AKCEA-ANGPTL3-LRx


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Genetically confirmed chylomicronemia syndrome. Fasting triglycerides greater than or equal to (>=) 750 milligrams per deciliter (mg/dL) [8.4 millimoles per liter (mmol/L)] at Screening. Key Exclusion Criteria: Diabetes mellitus if newly diagnosed or if glycated hemoglobin (HbA1c) >= 9.0%. Active pancreatitis within 2 weeks of screening. Acute coronary syndrome within 6 months of screening. Major surgery within 3 months of screening. Treatment with Glybera therapy within 2 years of screening. Previous treatment with AKCEA-ANGPTL3-LRx. Have any other conditions in the opinion of the investigator which could interfere with the patient 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKCEA-ANGPTL3-LRx 20 mg<br>Participants received a subcutaneous (SC) injection of AKCEA-ANGPTL3-LRx, 20 milligrams (mg), weekly (QW) for 13-weeks of treatment period. Participants were followed up to Week 26. | Drug: AKCEA-ANGPTL3-LRx<br>* AKCEA-ANGPTL3-LRx at dose 20 mg, administered via SC injection QW.<br>* Other names: Vupanorsen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline to Month 3 in Fasting Triglycerides (TG) | Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments. | Baseline to Month 3 | 
| Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG) | Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments. | Baseline to Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline to Month 3 in Fasting Angiopoietin-Like 3 (ANGPTL3) | Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments. | Baseline to Month 3 | 
| Percent Change From Baseline to Month 3 in Fasting Angiopoietin-like 3 (ANGPTL3) | Baseline was defined as the average of Day 1 predose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments. | Baseline to Month 3 | 
| Fasting Lipid and Lipoprotein Measurements at Month 3 | Fasting lipid and lipoprotein measurements included non-HDL-C, ApoB, HDL-C, ApoA-1, VLDL-C and LDL-C. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments. | Month 3 | 
| Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Other fasting lipid measurements included total cholesterol (TC), non-HDL-C, ApoB, HDL-C, ApoA-1, VLDL-C, and LDL-C. Baseline was defined as average of Day 1 predose fasting assessment and last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments. | Baseline to Month 3 | 
| Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Other fasting lipid measurements included TC, non-HDL-C, ApoB, HDL-C, ApoA-1, VLDL-C, and LDL-C. Baseline was defined as average of Day 1 predose fasting assessment and last fasting measurement prior to Day 1 pre-dose fasting assessment. Month 3 was defined as the average of Week 13 and Week 14 fasting assessments. | Baseline to Month 3 | 
| Change From Baseline to Day 92 in Maximum Postprandial Triglycerides (TG) | Participants consumed standardized pre-cooked meals (lunches and dinners and instructions for breakfasts and snacks) for 2 days prior to the postprandial assessments. Change from Baseline to Day 92 in maximum postprandial TG was assessed. | Baseline to Day 92 | 
| Number of Participants Who Experienced Abdominal Pain During the Treatment Period |  | Days 1, 29, 57 and 92 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. A TEAE was defined as any AE starting on or after the first dose of the study drug. | From time of informed consent to end of follow-up period (Up to Week 26) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Familial Lipoprotein Lipase Deficiency, Hyperlipoproteinemias, Familial Hyperlipoproteinemia Type 1, Hyperlipoproteinemia Type I, Hyperchylomicronemia, Familial, Lipoprotein Lipase Deficiency, Familial, Hyperlipidemias, Dyslipidemias, Lipid Metabolism Disorders, Lipid Metabolism, Inborn Errors, Metabolic Diseases, Metabolism, Inborn Errors, Genetic Diseases, Inborn