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CompletedNCT03360747Updated Jan 7, 2021Results posted

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

A Phase 2 interventional study of AKCEA-ANGPTL3-LRx in Familial Chylomicronemia Syndrome, Lipoprotein Lipase Deficiency and Hyperlipoproteinemia Type 1, sponsored by Akcea Therapeutics. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-01-07.

Sponsored by Akcea Therapeutics (part of Ionis Pharmaceuticals, Inc.) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
3
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • 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
03

In context

Hyperlipoproteinemia Type I

21 studies on the registry are indexed under Hyperlipoproteinemia Type I; 3 are open to participants now.

This study's enrollment of 3 is below the median of 14 across 11 interventional studies indexed under Hyperlipoproteinemia Type I.

Browse Hyperlipoproteinemia Type I studies →

Lead sponsor

Akcea Therapeutics is the lead sponsor of 15 studies on the registry; 1 is open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 8 (89%) have results posted.

Browse Akcea Therapeutics studies →All Ionis Pharmaceuticals, Inc. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
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 (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.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

HbA1c

A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
3 participants (actual)

Study arms

  • 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

Interventions

  • DrugAKCEA-ANGPTL3-LRx

    AKCEA-ANGPTL3-LRx at dose 20 mg, administered via SC injection QW.

    Also known as: ISIS 703802, IONIS-ANGPTL3-LRx, Vupanorsen

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline to Month 3

  2. 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.

    Time frame: Baseline to Month 3

Secondary outcomes

  1. 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.

    Time frame: Baseline to Month 3

  2. 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.

    Time frame: Baseline to Month 3

  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.

    Time frame: Month 3

  4. 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.

    Time frame: Baseline to Month 3

  5. 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.

    Time frame: Baseline to Month 3

  6. 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.

    Time frame: Baseline to Day 92

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

    Time frame: Days 1, 29, 57 and 92

  8. 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.

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

07

Results

Posted Jan 7, 2021

Participant flow

Participants took part in the study at 1 study site in Canada from 21-December-2017 to 4-September-2018.

Participant flow — Overall Study
MilestoneAKCEA-ANGPTL3-LRx 20 mg
Started3
Completed2
Not completed1
Withdrew: Voluntary withdrawal1

Outcome measures

PrimaryAbsolute 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.

Time frame:
Baseline to Month 3
Reported as:
Mean · mg/dL
Absolute Change From Baseline to Month 3 in Fasting Triglycerides (TG)
mg/dLAKCEA-ANGPTL3-LRx 20 mg
Absolute Change From Baseline to Month 3 in Fasting Triglycerides (TG)-550.00 ± 431.471
PrimaryPercent 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.

Time frame:
Baseline to Month 3
Reported as:
Mean · percent change
Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG)
percent changeAKCEA-ANGPTL3-LRx 20 mg
Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG)-32.83 ± 31.994
SecondaryAbsolute 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.

Time frame:
Baseline to Month 3
Reported as:
Mean · ng/mL
Absolute Change From Baseline to Month 3 in Fasting Angiopoietin-Like 3 (ANGPTL3)
ng/mLAKCEA-ANGPTL3-LRx 20 mg
Absolute Change From Baseline to Month 3 in Fasting Angiopoietin-Like 3 (ANGPTL3)-31.983 ± 5.4773
SecondaryPercent 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.

Time frame:
Baseline to Month 3
Reported as:
Mean · percent change
Percent Change From Baseline to Month 3 in Fasting Angiopoietin-like 3 (ANGPTL3)
percent changeAKCEA-ANGPTL3-LRx 20 mg
Percent Change From Baseline to Month 3 in Fasting Angiopoietin-like 3 (ANGPTL3)-51.249 ± 4.9093
SecondaryFasting 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.

Time frame:
Month 3
Reported as:
Mean · mg/dL
Fasting Lipid and Lipoprotein Measurements at Month 3
mg/dLAKCEA-ANGPTL3-LRx 20 mg
Non-HDL-C217.33 ± 119.618
ApoB64.53 ± 4.899
HDL-C13.0 ± 1.00
ApoA-177.3 ± 6.03
VLDL-C190.17 ± 128.861
LDL-C27.17 ± 10.324
SecondaryAbsolute 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.

Time frame:
Baseline to Month 3
Reported as:
Mean · mg/dL
Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters
mg/dLAKCEA-ANGPTL3-LRx 20 mg
Absolute Change From Baseline to Month 3 in TC-86.17 ± 48.581
Absolute Change From Baseline to Month 3:Non-HDL-C-83.83 ± 48.235
Absolute Change From Baseline to Month 3 in ApoB-8.12 ± 5.352
Absolute Change From Baseline to Month 3 in HDL-C-2.3 ± 0.58
Absolute Change From Baseline to Month 3 in ApoA-1-17.3 ± 11.93
Absolute Change From Baseline to Month 3 in VLDL-C-82.50 ± 51.215
Absolute Change From Baseline to Month 3 in LDL-C-1.33 ± 3.753
SecondaryPercent (%) 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.

Time frame:
Baseline to Month 3
Reported as:
Mean · percent change
Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters
percent changeAKCEA-ANGPTL3-LRx 20 mg
% Change From Baseline to Month 3 in TC-30.39 ± 20.436
% Change From Baseline to Month 3 in Non-HDL-C-31.49 ± 21.832
% Change From Baseline to Month 3 in ApoB-10.73 ± 6.021
% Change From Baseline to Month 3 in HDL-C-15.2 ± 3.22
% Change From Baseline to Month 3 in ApoA-1-17.8 ± 10.97
% Change From Baseline to Month 3 in VLDL-C-36.03 ± 28.044
% Change From Baseline to Month 3 in LDL-C-6.47 ± 13.426
SecondaryChange 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.

Time frame:
Baseline to Day 92
Reported as:
Mean · mg/dL
Change From Baseline to Day 92 in Maximum Postprandial Triglycerides (TG)
mg/dLAKCEA-ANGPTL3-LRx 20 mg
Change From Baseline to Day 92 in Maximum Postprandial Triglycerides (TG)-338.0 ± 38.22
SecondaryNumber of Participants Who Experienced Abdominal Pain During the Treatment Period
Time frame:
Days 1, 29, 57 and 92
Reported as:
Count of participants · Participants
Number of Participants Who Experienced Abdominal Pain During the Treatment Period
ParticipantsAKCEA-ANGPTL3-LRx 20 mg
Number of Participants Who Experienced Abdominal Pain During the Treatment Period1
SecondaryNumber 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.

Time frame:
From time of informed consent to end of follow-up period (Up to Week 26)
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
ParticipantsAKCEA-ANGPTL3-LRx 20 mg
Number of Participants With Treatment Emergent Adverse Events (TEAEs)3

Adverse events

Collected over From time of informed consent to end of follow-up period (Up to Week 26).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
AKCEA-ANGPTL3-LRx 20 mg0/3 (0%)0/3 (0%)3/3 (100%)
Most frequent other events
Most frequent other events
EventAKCEA-ANGPTL3-LRx 20 mg
HeadacheNervous system disorders2/3
AstheniaGeneral disorders1/3
Influenza like illnessGeneral disorders1/3
Back painMusculoskeletal and connective tissue disorders1/3
Musculoskeletal chest painMusculoskeletal and connective tissue disorders1/3
Vertigo positionalEar and labyrinth disorders1/3
InfluenzaInfections and infestations1/3
HyperlipidaemiaMetabolism and nutrition disorders1/3
Loss of libidoPsychiatric disorders1/3
Mood swingsPsychiatric disorders1/3

Baseline characteristics

Safety set included all participants who were enrolled and received at least 1 dose of study drug.

Age, Continuous
Age, Continuous(years)AKCEA-ANGPTL3-LRx 20 mg
Mean51.0 ± 15.72
Sex: Female, Male
Sex: Female, Male(Participants)AKCEA-ANGPTL3-LRx 20 mg
Female1
Male2
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AKCEA-ANGPTL3-LRx 20 mg
Hispanic or Latino0
Not Hispanic or Latino3
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)AKCEA-ANGPTL3-LRx 20 mg
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White3
More than one race0
Unknown or Not Reported0
Fasting Triglycerides (TG)
Fasting Triglycerides (TG)(milligrams per deciliter (mg/dL))AKCEA-ANGPTL3-LRx 20 mg
Mean2299.50 ± 961.139
Fasting Angiopoietin-Like 3 (ANGPTL3)
Fasting Angiopoietin-Like 3 (ANGPTL3)(nanograms per milliliter (ng/mL))AKCEA-ANGPTL3-LRx 20 mg
Mean62.433 ± 8.9030
Fasting Total Cholesterol (TC)
Fasting Total Cholesterol (TC)(mg/dL)AKCEA-ANGPTL3-LRx 20 mg
Mean316.50 ± 81.957
Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C)
Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C)(mg/dL)AKCEA-ANGPTL3-LRx 20 mg
Mean301.17 ± 82.791

6 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Investigative Site
    Montréal, Quebec H2W 1R7, Canada
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Dec 2017 to primary completion in Jun 2018, 5 months.

Results were first posted in Jan 2021, 2 years 6 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 18, 2017
First posted
Dec 4, 2017
StartActual
Dec 21, 2017
Primary completionActual
Jun 12, 2018
CompletionActual
Sep 4, 2018
Results first posted
Jan 7, 2021
Last update
Jan 7, 2021
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jan 7, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03360747
Lead sponsor
Akcea Therapeutics
Collaborators
Ionis Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Dec 4, 2017
Start date
Dec 21, 2017
Primary completion
Jun 12, 2018
Completion
Sep 4, 2018
Results posted
Jan 7, 2021
Last update
Jan 7, 2021

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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