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

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)

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.

Study Overview

• Status: Completed
• Conditions: Familial Chylomicronemia Syndrome; Lipoprotein Lipase Deficiency; Hyperlipoproteinemia Type 1
• Intervention / Treatment: Drug: AKCEA-ANGPTL3-LRx

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2W 1R7
      • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AKCEA-ANGPTL3-LRx 20 mg; 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; AKCEA-ANGPTL3-LRx at dose 20 mg, administered via SC injection QW.; Other Names: ISIS 703802; IONIS-ANGPTL3-LRx; Vupanorsen

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Akcea Therapeutics
• Collaborators: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 21, 2017
• Primary Completion (ACTUAL): June 12, 2018
• Study Completion (ACTUAL): September 4, 2018

Study Registration Dates

• First Submitted: November 18, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (ACTUAL): December 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 7, 2021
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Genetic Diseases, Inborn; Lipid Metabolism Disorders; Metabolic Diseases; Metabolism, Inborn Errors; Dyslipidemias; Hyperlipidemias; Familial Lipoprotein Lipase Deficiency; Hyperlipoproteinemias; Familial Hyperlipoproteinemia Type 1; Hyperchylomicronemia, Familial; Lipoprotein Lipase Deficiency, Familial; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemia Type I
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Lipid Metabolism, Inborn Errors; Syndrome; Hyperlipidemias; Hyperlipoproteinemias; Hyperlipoproteinemia Type I
• Other Study ID Numbers: ISIS 703802-CS3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes