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

Phase 2

Completed

Conditions: Familial Chylomicronemia Syndrome
Hyperlipoproteinemia Type 1
Lipoprotein Lipase Deficiency

Interventions: Drug: AKCEA-ANGPTL3-LRx

Registration Number: NCT03360747

Lead Sponsor: Akcea Therapeutics

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AKCEA-ANGPTL3-LRx 20 mg	AKCEA-ANGPTL3-LRx	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.

Primary Outcome Measures

Name	Time	Method
Absolute Change From Baseline to Month 3 in Fasting Triglycerides (TG)	Baseline to Month 3	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.
Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG)	Baseline to Month 3	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.

Secondary Outcome Measures

Name	Time	Method
Absolute Change From Baseline to Month 3 in Fasting Angiopoietin-Like 3 (ANGPTL3)	Baseline to Month 3	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.
Percent Change From Baseline to Month 3 in Fasting Angiopoietin-like 3 (ANGPTL3)	Baseline to Month 3	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.
Fasting Lipid and Lipoprotein Measurements at Month 3	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.
Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters	Baseline to Month 3	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.
Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters	Baseline to Month 3	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.
Change From Baseline to Day 92 in Maximum Postprandial Triglycerides (TG)	Baseline to Day 92	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.
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)	From time of informed consent to end of follow-up period (Up to Week 26)	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.