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

• AKCEA-ANGPTL3-LRx (Drug), also known as ISIS 703802, IONIS-ANGPTL3-LRx, Vupanorsen: AKCEA-ANGPTL3-LRx at dose 20 mg, administered via SC injection QW.

Primary outcomes

• 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 outcomes

• 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.

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Absolute Change From Baseline to Month 3 in Fasting Triglycerides (TG) (Primary), Mean, mg/dL: AKCEA-ANGPTL3-LRx 20 mg -550.00 +/- 431.471
• Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG) (Primary), Mean, percent change: AKCEA-ANGPTL3-LRx 20 mg -32.83 +/- 31.994
• Absolute Change From Baseline to Month 3 in Fasting Angiopoietin-Like 3 (ANGPTL3) (Secondary), Mean, ng/mL: AKCEA-ANGPTL3-LRx 20 mg -31.983 +/- 5.4773
• Percent Change From Baseline to Month 3 in Fasting Angiopoietin-like 3 (ANGPTL3) (Secondary), Mean, percent change: AKCEA-ANGPTL3-LRx 20 mg -51.249 +/- 4.9093
• Fasting Lipid and Lipoprotein Measurements at Month 3 (Secondary), Mean, mg/dL: AKCEA-ANGPTL3-LRx 20 mg 217.33 +/- 119.618
• Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters (Secondary), Mean, mg/dL: AKCEA-ANGPTL3-LRx 20 mg -86.17 +/- 48.581
• Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters (Secondary), Mean, percent change: AKCEA-ANGPTL3-LRx 20 mg -30.39 +/- 20.436
• Change From Baseline to Day 92 in Maximum Postprandial Triglycerides (TG) (Secondary), Mean, mg/dL: AKCEA-ANGPTL3-LRx 20 mg -338.0 +/- 38.22
• Number of Participants Who Experienced Abdominal Pain During the Treatment Period (Secondary), Count of participants, Participants: AKCEA-ANGPTL3-LRx 20 mg 1
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Secondary), Count of participants, Participants: AKCEA-ANGPTL3-LRx 20 mg 3

Adverse events

Time frame: From time of informed consent to end of follow-up period (Up to Week 26).

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2017-10-26)