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

Primary Purpose

Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency, Hyperlipoproteinemia Type 1

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
AKCEA-ANGPTL3-LRx
Sponsored by
Akcea Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Familial Chylomicronemia Syndrome focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AKCEA-ANGPTL3-LRx 20 mg

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
Number of Participants Who Experienced Abdominal Pain During the Treatment Period
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.

Full Information

First Posted
November 18, 2017
Last Updated
December 11, 2020
Sponsor
Akcea Therapeutics
Collaborators
Ionis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03360747
Brief Title
Phase 2 Study of AKCEA-ANGPTL3-LRx (ISIS 703802) in Participants With Familial Chylomicronemia Syndrome (FCS)
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
December 21, 2017 (Actual)
Primary Completion Date
June 12, 2018 (Actual)
Study Completion Date
September 4, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akcea Therapeutics
Collaborators
Ionis Pharmaceuticals, Inc.

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency, Hyperlipoproteinemia Type 1
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AKCEA-ANGPTL3-LRx 20 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AKCEA-ANGPTL3-LRx
Other Intervention Name(s)
ISIS 703802, IONIS-ANGPTL3-LRx, Vupanorsen
Intervention Description
AKCEA-ANGPTL3-LRx at dose 20 mg, administered via SC injection QW.
Primary Outcome Measure Information:
Title
Absolute Change From Baseline to Month 3 in Fasting Triglycerides (TG)
Description
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.
Time Frame
Baseline to Month 3
Title
Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG)
Description
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.
Time Frame
Baseline to Month 3
Secondary Outcome Measure Information:
Title
Absolute Change From Baseline to Month 3 in Fasting Angiopoietin-Like 3 (ANGPTL3)
Description
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.
Time Frame
Baseline to Month 3
Title
Percent Change From Baseline to Month 3 in Fasting Angiopoietin-like 3 (ANGPTL3)
Description
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.
Time Frame
Baseline to Month 3
Title
Fasting Lipid and Lipoprotein Measurements at Month 3
Description
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.
Time Frame
Month 3
Title
Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Description
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.
Time Frame
Baseline to Month 3
Title
Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
Description
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.
Time Frame
Baseline to Month 3
Title
Change From Baseline to Day 92 in Maximum Postprandial Triglycerides (TG)
Description
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.
Time Frame
Baseline to Day 92
Title
Number of Participants Who Experienced Abdominal Pain During the Treatment Period
Time Frame
Days 1, 29, 57 and 92
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
From time of informed consent to end of follow-up period (Up to Week 26)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Investigative Site
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2W 1R7
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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