Familial Chylomicronemia Syndrome, Hyperlipoproteinemia Type 1, Lipoprotein Lipase Deficiency
Conditions
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
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.
Interventions
AKCEA-ANGPTL3-LRx at dose 20 mg, administered via SC injection QW.
Sponsors
Ionis Pharmaceuticals, Inc.
Akcea Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada
Participant flow
Recruitment details
Participants took part in the study at 1 study site in Canada from 21-December-2017 to 4-September-2018.
Pre-assignment details
A total of 4 participants were screened, 3 of whom were enrolled and treated with at least one dose of study drug and were included in the analysis. This study consisted of up to an 8-week screening period, a 13-week treatment period and a 13-week follow-up (post-treatment evaluation) period.
Participants by arm
| Arm | Count |
|---|---|
| AKCEA-ANGPTL3-LRx 20 mg Participants received a SC injection of AKCEA-ANGPTL3-LRx, 20 mg, QW for 13-weeks of treatment period. Participants were followed up to Week 26. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Voluntary Withdrawal | 1 |
Baseline characteristics
| Characteristic | AKCEA-ANGPTL3-LRx 20 mg |
|---|---|
| Age, Continuous | 51.0 years STANDARD_DEVIATION 15.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fasting Angiopoietin-Like 3 (ANGPTL3) | 62.433 nanograms per milliliter (ng/mL) STANDARD_DEVIATION 8.903 |
| Fasting Apolipoprotein A-1 (ApoA-1) | 94.7 mg/dL STANDARD_DEVIATION 7.51 |
| Fasting Apolipoprotein B (ApoB) | 72.65 mg/dL STANDARD_DEVIATION 9.406 |
| Fasting High Density Lipoprotein Cholesterol (HDL-C) | 15.3 mg/dL STANDARD_DEVIATION 1.15 |
| Fasting Low Density Lipoprotein Cholesterol (LDL-C) | 28.50 mg/dL STANDARD_DEVIATION 6.946 |
| Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) | 301.17 mg/dL STANDARD_DEVIATION 82.791 |
| Fasting Total Cholesterol (TC) | 316.50 mg/dL STANDARD_DEVIATION 81.957 |
| Fasting Triglycerides (TG) | 2299.50 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 961.139 |
| Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) | 272.67 mg/dL STANDARD_DEVIATION 89.326 |
| Maximum Postprandial Triglycerides | 2454.81 mg/dL STANDARD_DEVIATION 1019.963 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
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
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Fasting Triglycerides (TG) | -550.00 mg/dL | Standard Deviation 431.471 |
Primary
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
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Percent Change From Baseline to Month 3 in Fasting Triglycerides (TG) | -32.83 percent change | Standard Deviation 31.994 |
Secondary
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
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Fasting Angiopoietin-Like 3 (ANGPTL3) | -31.983 ng/mL | Standard Deviation 5.4773 |
Secondary
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
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Absolute Change From Baseline to Month 3 in TC | -86.17 mg/dL | Standard Deviation 48.581 |
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Absolute Change From Baseline to Month 3:Non-HDL-C | -83.83 mg/dL | Standard Deviation 48.235 |
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Absolute Change From Baseline to Month 3 in ApoB | -8.12 mg/dL | Standard Deviation 5.352 |
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Absolute Change From Baseline to Month 3 in HDL-C | -2.3 mg/dL | Standard Deviation 0.58 |
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Absolute Change From Baseline to Month 3 in ApoA-1 | -17.3 mg/dL | Standard Deviation 11.93 |
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Absolute Change From Baseline to Month 3 in VLDL-C | -82.50 mg/dL | Standard Deviation 51.215 |
| AKCEA-ANGPTL3-LRx 20 mg | Absolute Change From Baseline to Month 3 in Other Fasting Lipid Parameters | Absolute Change From Baseline to Month 3 in LDL-C | -1.33 mg/dL | Standard Deviation 3.753 |
Secondary
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
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Change From Baseline to Day 92 in Maximum Postprandial Triglycerides (TG) | -338.0 mg/dL | Standard Deviation 38.22 |
Secondary
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
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Fasting Lipid and Lipoprotein Measurements at Month 3 | Non-HDL-C | 217.33 mg/dL | Standard Deviation 119.618 |
| AKCEA-ANGPTL3-LRx 20 mg | Fasting Lipid and Lipoprotein Measurements at Month 3 | ApoB | 64.53 mg/dL | Standard Deviation 4.899 |
| AKCEA-ANGPTL3-LRx 20 mg | Fasting Lipid and Lipoprotein Measurements at Month 3 | HDL-C | 13.0 mg/dL | Standard Deviation 1 |
| AKCEA-ANGPTL3-LRx 20 mg | Fasting Lipid and Lipoprotein Measurements at Month 3 | ApoA-1 | 77.3 mg/dL | Standard Deviation 6.03 |
| AKCEA-ANGPTL3-LRx 20 mg | Fasting Lipid and Lipoprotein Measurements at Month 3 | VLDL-C | 190.17 mg/dL | Standard Deviation 128.861 |
| AKCEA-ANGPTL3-LRx 20 mg | Fasting Lipid and Lipoprotein Measurements at Month 3 | LDL-C | 27.17 mg/dL | Standard Deviation 10.324 |
Secondary
Number of Participants Who Experienced Abdominal Pain During the Treatment Period
Time frame: Days 1, 29, 57 and 92
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Number of Participants Who Experienced Abdominal Pain During the Treatment Period | 1 Participants |
Secondary
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)
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
Secondary
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
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Percent Change From Baseline to Month 3 in Fasting Angiopoietin-like 3 (ANGPTL3) | -51.249 percent change | Standard Deviation 4.9093 |
Secondary
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
Population: Safety set included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AKCEA-ANGPTL3-LRx 20 mg | Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters | % Change From Baseline to Month 3 in TC | -30.39 percent change | Standard Deviation 20.436 |
| AKCEA-ANGPTL3-LRx 20 mg | Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters | % Change From Baseline to Month 3 in Non-HDL-C | -31.49 percent change | Standard Deviation 21.832 |
| AKCEA-ANGPTL3-LRx 20 mg | Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters | % Change From Baseline to Month 3 in ApoB | -10.73 percent change | Standard Deviation 6.021 |
| AKCEA-ANGPTL3-LRx 20 mg | Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters | % Change From Baseline to Month 3 in HDL-C | -15.2 percent change | Standard Deviation 3.22 |
| AKCEA-ANGPTL3-LRx 20 mg | Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters | % Change From Baseline to Month 3 in ApoA-1 | -17.8 percent change | Standard Deviation 10.97 |
| AKCEA-ANGPTL3-LRx 20 mg | Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters | % Change From Baseline to Month 3 in VLDL-C | -36.03 percent change | Standard Deviation 28.044 |
| AKCEA-ANGPTL3-LRx 20 mg | Percent (%) Change From Baseline to Month 3 in Other Fasting Lipid Parameters | % Change From Baseline to Month 3 in LDL-C | -6.47 percent change | Standard Deviation 13.426 |