Heterozygous Familial Hypercholesterolemia
Conditions
Keywords
Hypercholesterolemia, Elevated Cholesterol, High Cholesterol, Heterozygous Familial Hypercholesterolemia, PCSK9 mutations, Paediatric, pediatric, Childhood Familial Hypercholesterolemia
Brief summary
A study to assess safety and efficacy of evolocumab (AMG-145) in paediatric subjects aged 10-17 years diagnosed with heterozygous familial hypercholesterolemia.
Detailed description
A study to evaluate the effect of 24 weeks of subcutaneous (SC) evolocumab compared with placebo, when added to standard of care, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in pediatric subjects 10 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH).
Interventions
DRUGEvolocumab
Dose of subcutaneous evolocumab every 4 weeks
DRUGPlacebo
Dose of subcutaneous placebo treatment every 4 weeks
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 10 to ≤ 17 years of age (before 18th birthday) * Diagnosis of heterozygous familial hypercholesterolemia * On an approved statin with stable optimized dose for ≥ 4 weeks * Other lipid-lowering therapy stable for ≥ 4 weeks (fibrates must be stable for ≥ 6 weeks) * Fasting LDL-C ≥ 130 mg/dL (3.4 mmol/L) * Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)
Exclusion criteria
* Type 1 diabetes, or type 2 diabetes that is or poorly controlled * Uncontrolled hyperthyroidism or hypothyroidism * Cholesterylester transfer protein (CETP) inhibitor in the last 12 months, or mipomersen or lomitapide in the last 5 months * Previously received evolocumab or any other investigational therapy to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9). * Lipid apheresis within the last 12 weeks prior to screening. * Homozygous familial hypercholesterolemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 24 in LDL-C | Baseline, Week 24 | Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from interactive voice response system \[IVRS\]), scheduled visit and the interaction of treatment with scheduled visit as covariates. The model uses an unstructured covariance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in LDL-C | Baseline, Week 24 | Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates. |
| Percent Change From Baseline to Week 24 in Non-HDL-C | Baseline, Week 24 | Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates |
| Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB) | Baseline, Week 24 | Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates. |
| Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio | Baseline, Week 24 | Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates. |
| Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio | Baseline, Week 24 | Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | From first dose of study drug up to and including 30 days after the last dose or end of study date (Week 24), whichever was earlier. Mean (SD) duration on study was 5.664 (0.278) and 5.608 (0.137) months for Placebo and EvoMab arms, respectively. | An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. An SAE is defined as an adverse event that: is fatal; is a life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other medically important serious event. Events were graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading scale (1=mild; 2=moderate; 3=severe; 4=life-threatening; 5=death). Events were defined as treatment emergent if they occurred after the first dose of study drug and up to and including 30 days after the last dose or the end of study date, whichever is earlier. |
| Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C | Baseline, Week 22, Week 24 | Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates. |
| Change From Baseline Over Time in Systolic Blood Pressure | Baseline, Week 4, Week 12, Week 20, Week 22, Week 24 | — |
| Change From Baseline Over Time in Diastolic Blood Pressure | Baseline, Week 4, Week 12, Week 20, Week 22, Week 24 | — |
| Change From Baseline Over Time in Heart Rate | Baseline, Week 4, Week 12, Week 20, Week 22, Week 24 | — |
| Number of Participants Testing Positive for Anti-Evolocumab Antibodies | up to Week 24 | — |
| Serum Evolocumab Concentrations Over Time | Week 12, Week 22, Week 24 | — |
| Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3 | Week 24 | Laboratory toxicity grading was based on NCI CTCAE grading. Grade 3 indicates severe toxicity and Grade 4 indicates life-threatening toxicity. Values representing a worsening from baseline are shown. |
Countries
Australia, Austria, Belgium, Brazil, Canada, Colombia, Czechia, Finland, Greece, Hungary, Italy, Malaysia, Netherlands, New Zealand, Norway, Poland, Portugal, Russia, Slovenia, South Africa, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled from 24 March 2016 to 30 May 2019 at 8 research centers in North America, 30 research centers in Europe, 6 research centers in Latin America, and 3 research centers in Asia Pacific.
Pre-assignment details
Participants were randomized in a 2:1 ratio to receive 24 weeks of monthly (QM) evolocumab or placebo. Randomization was stratified by screening low-density lipoprotein cholesterol (LDL-C; \< 160 mg/dL vs ≥ 160 mg/dL) and age (\< 14 years vs ≥ 14 years).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching subcutaneous injection QM | 53 |
| EvoMab 420 mg QM Evolocumab subcutaneous injection QM | 104 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | EvoMab 420 mg QM |
|---|---|---|---|
| Age, Continuous | 13.7 years STANDARD_DEVIATION 2.5 | 13.7 years STANDARD_DEVIATION 2.4 | 13.7 years STANDARD_DEVIATION 2.3 |
| ApoB/Apolipoprotein A1 (ApoA1) Ratio | 0.938 ratio STANDARD_DEVIATION 0.255 | 0.960 ratio STANDARD_DEVIATION 0.287 | 0.970 ratio STANDARD_DEVIATION 0.302 |
| Apolipoprotein B (ApoB) | 119.4 mg/dL STANDARD_DEVIATION 27.9 | 122.0 mg/dL STANDARD_DEVIATION 27.3 | 123.3 mg/dL STANDARD_DEVIATION 27.1 |
| Diastolic Blood Pressure | 67.2 mmHg STANDARD_DEVIATION 8.7 | 66.6 mmHg STANDARD_DEVIATION 8.1 | 66.3 mmHg STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 13 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 144 Participants | 98 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Heart Rate | 74.3 beats per minute STANDARD_DEVIATION 11.7 | 74.4 beats per minute STANDARD_DEVIATION 11.2 | 74.5 beats per minute STANDARD_DEVIATION 11.1 |
| LDL-C | 183.0 mg/dL STANDARD_DEVIATION 47.2 | 184.3 mg/dL STANDARD_DEVIATION 45.6 | 185.0 mg/dL STANDARD_DEVIATION 45 |
| Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) | 200.2 mg/dL STANDARD_DEVIATION 48.2 | 202.6 mg/dL STANDARD_DEVIATION 47.5 | 203.8 mg/dL STANDARD_DEVIATION 47.3 |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Black (or African American) | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Other, Not Specified | 9 participants | 20 participants | 11 participants |
| Race/Ethnicity, Customized White | 44 participants | 133 participants | 89 participants |
| Sex: Female, Male Female | 27 Participants | 88 Participants | 61 Participants |
| Sex: Female, Male Male | 26 Participants | 69 Participants | 43 Participants |
| Stratification Factor: Age Group < 14 years | 25 participants | 73 participants | 48 participants |
| Stratification Factor: Age Group ≥ 14 years | 28 participants | 84 participants | 56 participants |
| Stratification Factor: Screening LDL-C Level < 160 mg/dL | 16 participants | 49 participants | 33 participants |
| Stratification Factor: Screening LDL-C Level ≥ 160 mg/dL | 37 participants | 108 participants | 71 participants |
| Systolic Blood Pressure | 112.0 mmHg STANDARD_DEVIATION 12.1 | 111.2 mmHg STANDARD_DEVIATION 11.7 | 110.8 mmHg STANDARD_DEVIATION 11.5 |
| Total Cholesterol/HDL-C Ratio | 5.517 ratio STANDARD_DEVIATION 1.492 | 5.639 ratio STANDARD_DEVIATION 1.694 | 5.702 ratio STANDARD_DEVIATION 1.791 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 105 |
| other Total, other adverse events | 19 / 53 | 41 / 104 |
| serious Total, serious adverse events | 0 / 53 | 1 / 104 |
Outcome results
Primary
Percent Change From Baseline to Week 24 in LDL-C
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from interactive voice response system \[IVRS\]), scheduled visit and the interaction of treatment with scheduled visit as covariates. The model uses an unstructured covariance.
Time frame: Baseline, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in LDL-C | -6.23 percent change | Standard Error 3.08 |
| EvoMab 420 mg QM | Percent Change From Baseline to Week 24 in LDL-C | -44.53 percent change | Standard Error 2.17 |
p-value: <0.000195% CI: [-45.54, -31.06]repeated measures model
p-value: <0.0001sequential testing/Hochberg procedure
Secondary
Change From Baseline Over Time in Diastolic Blood Pressure
Time frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 12 | -2.2 mmHg | Standard Deviation 10 |
| Placebo | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 22 | -1.5 mmHg | Standard Deviation 9.3 |
| Placebo | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 20 | -3.3 mmHg | Standard Deviation 7.6 |
| Placebo | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 24 | -0.5 mmHg | Standard Deviation 9 |
| Placebo | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 4 | -2.5 mmHg | Standard Deviation 9.5 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 24 | 0.3 mmHg | Standard Deviation 8.6 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 4 | -1.5 mmHg | Standard Deviation 7.3 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 12 | 0.5 mmHg | Standard Deviation 8.9 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 20 | -0.6 mmHg | Standard Deviation 7.7 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Diastolic Blood Pressure | Change at Week 22 | 2.9 mmHg | Standard Deviation 8 |
Secondary
Change From Baseline Over Time in Heart Rate
Time frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Heart Rate | Change at Week 12 | -0.5 beats per minute | Standard Deviation 11.5 |
| Placebo | Change From Baseline Over Time in Heart Rate | Change at Week 22 | 1.3 beats per minute | Standard Deviation 13.5 |
| Placebo | Change From Baseline Over Time in Heart Rate | Change at Week 4 | 2.1 beats per minute | Standard Deviation 11 |
| Placebo | Change From Baseline Over Time in Heart Rate | Change at Week 24 | 0.2 beats per minute | Standard Deviation 13 |
| Placebo | Change From Baseline Over Time in Heart Rate | Change at Week 20 | -1.1 beats per minute | Standard Deviation 10.3 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Heart Rate | Change at Week 24 | -1.8 beats per minute | Standard Deviation 11.8 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Heart Rate | Change at Week 4 | 0.1 beats per minute | Standard Deviation 10.8 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Heart Rate | Change at Week 12 | -1.3 beats per minute | Standard Deviation 10.2 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Heart Rate | Change at Week 20 | 1.1 beats per minute | Standard Deviation 11.5 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Heart Rate | Change at Week 22 | -0.6 beats per minute | Standard Deviation 11.3 |
Secondary
Change From Baseline Over Time in Systolic Blood Pressure
Time frame: Baseline, Week 4, Week 12, Week 20, Week 22, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 12 | -0.6 mmHg | Standard Deviation 10.3 |
| Placebo | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 22 | 1.0 mmHg | Standard Deviation 10.9 |
| Placebo | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 20 | -2.1 mmHg | Standard Deviation 7.7 |
| Placebo | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 24 | -0.6 mmHg | Standard Deviation 11.4 |
| Placebo | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 4 | -0.1 mmHg | Standard Deviation 11.3 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 24 | 0.6 mmHg | Standard Deviation 10.7 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 4 | -0.7 mmHg | Standard Deviation 9.4 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 12 | 0.3 mmHg | Standard Deviation 9.6 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 20 | 0.1 mmHg | Standard Deviation 10.1 |
| EvoMab 420 mg QM | Change From Baseline Over Time in Systolic Blood Pressure | Change at Week 22 | 1.1 mmHg | Standard Deviation 10 |
Secondary
Change From Baseline to Week 24 in LDL-C
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in LDL-C | -9.0 mg/dL | Standard Error 6.2 |
| EvoMab 420 mg QM | Change From Baseline to Week 24 in LDL-C | -77.5 mg/dL | Standard Error 4.4 |
p-value: <0.000195% CI: [-83.1, -54]repeated measures model
p-value: <0.0001sequential testing/Hochberg procedure
Secondary
Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Week 22, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C | -5.87 percent change | Standard Error 2.66 |
| EvoMab 420 mg QM | Mean Percent Change From Baseline to Mean of Weeks 22 and 24 in LDL-C | -47.95 percent change | Standard Error 1.92 |
p-value: <0.000195% CI: [-48.34, -35.83]repeated measures model
p-value: <0.0001sequential testing/Hochberg procedure
Secondary
Number of Participants Testing Positive for Anti-Evolocumab Antibodies
Time frame: up to Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants receiving evolocumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EvoMab 420 mg QM | Number of Participants Testing Positive for Anti-Evolocumab Antibodies | Binding antibody positive at anytime | 0 Participants |
| EvoMab 420 mg QM | Number of Participants Testing Positive for Anti-Evolocumab Antibodies | Neutralizing antibody positive at anytime | 0 Participants |
Secondary
Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3
Laboratory toxicity grading was based on NCI CTCAE grading. Grade 3 indicates severe toxicity and Grade 4 indicates life-threatening toxicity. Values representing a worsening from baseline are shown.
Time frame: Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3 | High Total Bilirubin - Grade 3 | 1 participants |
| Placebo | Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3 | High Total Cholesterol - Grade 3 | 1 participants |
| Placebo | Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3 | High Uric Acid - Grade 3 | 2 participants |
| EvoMab 420 mg QM | Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3 | High Total Bilirubin - Grade 3 | 0 participants |
| EvoMab 420 mg QM | Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3 | High Total Cholesterol - Grade 3 | 1 participants |
| EvoMab 420 mg QM | Number of Participants With Maximum Post-Baseline Laboratory Toxicities of Grade ≥ 3 | High Uric Acid - Grade 3 | 8 participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs
An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have a causal relationship with study treatment. An SAE is defined as an adverse event that: is fatal; is a life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other medically important serious event. Events were graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading scale (1=mild; 2=moderate; 3=severe; 4=life-threatening; 5=death). Events were defined as treatment emergent if they occurred after the first dose of study drug and up to and including 30 days after the last dose or the end of study date, whichever is earlier.
Time frame: From first dose of study drug up to and including 30 days after the last dose or end of study date (Week 24), whichever was earlier. Mean (SD) duration on study was 5.664 (0.278) and 5.608 (0.137) months for Placebo and EvoMab arms, respectively.
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Grade ≥ 2 TEAEs | 22 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Device-Related Grade ≥ 3 TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Grade ≥ 3 TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Fatal TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Grade ≥ 4 TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Device-Related Grade ≥ 4 TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Serious TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Device-Related Grade ≥ 2 TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | TEAEs Leading to DC of Study Drug | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Serious Device-Related TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Serious TEAEs Leading to DC of Study Drug | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | All TEAEs | 34 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Non-Serious TEAEs Leading to DC of Study Drug | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Device-Related TEAEs | 2 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Serious Device-Related TEAEs | 0 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Fatal TEAEs | 0 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Device-Related TEAEs | 3 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Device-Related Grade ≥ 2 TEAEs | 0 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Device-Related Grade ≥ 3 TEAEs | 0 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Device-Related Grade ≥ 4 TEAEs | 0 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | All TEAEs | 64 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Grade ≥ 2 TEAEs | 46 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Grade ≥ 3 TEAEs | 4 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Grade ≥ 4 TEAEs | 0 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Serious TEAEs | 1 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | TEAEs Leading to DC of Study Drug | 1 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Serious TEAEs Leading to DC of Study Drug | 0 participants |
| EvoMab 420 mg QM | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation (DC), Fatal TEAEs, and Device-Related TEAEs | Non-Serious TEAEs Leading to DC of Study Drug | 1 participants |
Secondary
Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio | -0.63 percent change | Standard Error 2.8 |
| EvoMab 420 mg QM | Percent Change From Baseline to Week 24 in ApoB:ApoA1 Ratio | -37.02 percent change | Standard Error 1.95 |
p-value: <0.000195% CI: [-42.97, -29.8]repeated measures model
p-value: <0.0001sequential testing/Hochberg procedure
Secondary
Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB)
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB) | -2.37 percent change | Standard Error 2.7 |
| EvoMab 420 mg QM | Percent Change From Baseline to Week 24 in Apoliprotein-B (ApoB) | -34.85 percent change | Standard Error 1.88 |
p-value: <0.000195% CI: [-38.82, -26.13]repeated measures model
p-value: <0.0001sequential testing/Hochberg procedure
Secondary
Percent Change From Baseline to Week 24 in Non-HDL-C
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates
Time frame: Baseline, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in Non-HDL-C | -6.14 percent change | Standard Error 2.87 |
| EvoMab 420 mg QM | Percent Change From Baseline to Week 24 in Non-HDL-C | -41.19 percent change | Standard Error 2.01 |
p-value: <0.000195% CI: [-41.79, -28.3]repeated measures model
p-value: <0.0001sequential testing/Hochberg procedure
Secondary
Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio
Least squares mean is from the repeated measures model which includes treatment group, stratification factors of age and screening LDL-C (from IVRS), scheduled visit and the interaction of treatment with scheduled visit as covariates.
Time frame: Baseline, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio | -4.66 percent change | Standard Error 2.6 |
| EvoMab 420 mg QM | Percent Change From Baseline to Week 24 in Total Cholesterol/HDL-C Ratio | -34.96 percent change | Standard Error 1.82 |
p-value: <0.000195% CI: [-36.4, -24.21]repeated measures model
p-value: <0.0001sequential testing/Hochberg procedure
Secondary
Serum Evolocumab Concentrations Over Time
Time frame: Week 12, Week 22, Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Evolocumab Concentrations Over Time | Week 12 | 22400 ng/mL | Standard Deviation 14700 |
| Placebo | Serum Evolocumab Concentrations Over Time | Week 22 | 64900 ng/mL | Standard Deviation 34400 |
| Placebo | Serum Evolocumab Concentrations Over Time | Week 24 | 25800 ng/mL | Standard Deviation 19200 |