Hypercholesterolemia
Conditions
Brief summary
The primary objective of the study is to evaluate the reduction of LDL-C by evinacumab in comparison to placebo after 16 weeks in patients with primary hypercholesterolemia (HeFH, or non-HeFH with a history of clinical ASCVD) with persistent hypercholesterolemia despite receiving maximally-tolerated LMT. Persistent hypercholesterolemia is defined as LDL-C ≥70 mg/dL (1.81 mmol/L) for those patients with clinical ASCVD and LDL-C ≥100 mg/dL (2.59 mmol/L) for those patients without clinical ASCVD.
Interventions
DRUGEvinacumab
SC or IV administration
DRUGMatching placebo
SC or IV administration
OTHERBackground Lipid Modifying Therapy (LMT)
All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
The inclusion/
Exclusion criteria
below, include, but are not limited to, the following: Key Inclusion Criteria: 1. Men and women, ages 18 through 80 at the screening visit 2. Diagnosis of primary hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD 3. A history of clinical ASCVD, for those patients who are non-HeFH. 4. Receiving a stable maximally tolerated statin (± ezetimibe) for at least 4 weeks at screening 5. For those patients with HeFH who are not receiving a statin at screening, documentation of inability to tolerate at least 2 statins. 6. Receiving alirocumab 150 mg SC Q2W, OR evolocumab 140 mg SC Q2W or 420 mg SC Q4W for at least 8 weeks prior to the screening visit 7. For those patients with a history of clinical ASCVD, serum LDL-C ≥ 70 mg/dL at screening (1 repeat lab is allowed) 8. For those patients without a history of clinical ASCVD, serum LDL-C ≥ 100 mg/dL at screening (1 repeat lab is allowed) 9. Provide signed informed consent Key
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand) | Baseline and Week 16 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Apo B at Week 24 (ITT Estimand) | Baseline and Week 24 | — |
| Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand) | Baseline and Week 16 | — |
| Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand) | Baseline and Week 24 | — |
| Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | Week 16 | — |
| Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | Week 16 | — |
| Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand) | Week 16 | Percentage of Participants with Calculated LDL-C \< 50 milligrams/deciliter (mg/dL) \[1.30 Millimoles per liter (mmol/L)\] at Week 16 (ITT Estimand) |
| Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand) | Baseline and Week 16 | — |
| Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand) | Baseline and Week 16 | — |
| Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand) | Baseline and Week 24 | — |
| Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand) | Baseline and Week 16 | — |
| Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand) | Baseline and Week 24 | — |
| Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand) | Baseline and Week 16 | — |
| Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand) | Baseline and Week 24 | — |
| Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand) | Baseline and Week 24 | — |
Countries
Australia, Austria, Canada, Czechia, Denmark, France, Israel, Italy, Japan, Jordan, Netherlands, New Zealand, Norway, Poland, Russia, South Africa, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 327 participants were screened and 272 participants randomized. Six participants were randomized but never treated.
Participants by arm
| Arm | Count |
|---|---|
| Group A: Placebo SC QW (DBTP) Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period | 39 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period | 39 |
| Group A: Evinacumab 300 mg SC QW (DBTP) Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period | 42 |
| Group A: Evinacumab 450 mg SC QW (DBTP) Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period | 40 |
| Group B: Placebo IV Q4W (DBTP to OLTP) Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP | 33 |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP | 35 |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP | 38 |
| Total | 266 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Double-blind Treatment Period (DBTP) | Adverse Event | 2 | 2 | 0 | 0 | 1 | 2 | 2 |
| Double-blind Treatment Period (DBTP) | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Double-blind Treatment Period (DBTP) | Physician Decision | 6 | 5 | 8 | 6 | 0 | 0 | 0 |
| Double-blind Treatment Period (DBTP) | Protocol Violation | 0 | 0 | 1 | 2 | 0 | 0 | 2 |
| Double-blind Treatment Period (DBTP) | Withdrawal by Subject | 1 | 1 | 2 | 2 | 0 | 1 | 0 |
| Open-Label Treatment Period (OLTP) | Noncompliance with protocol | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Open-Label Treatment Period (OLTP) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Group B: Placebo IV Q4W (DBTP to OLTP) | Group A: Evinacumab 450 mg SC QW (DBTP) | Group A: Evinacumab 300 mg SC QW (DBTP) | Group A: Evinacumab 300 mg SC Q2W (DBTP) | Group A: Placebo SC QW (DBTP) |
|---|---|---|---|---|---|---|---|---|
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 214 Participants | 33 Participants | 28 Participants | 26 Participants | 30 Participants | 34 Participants | 29 Participants | 34 Participants |
| Age, Customized From 65-84 years | 52 Participants | 5 Participants | 7 Participants | 7 Participants | 10 Participants | 8 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 2 Participants | 7 Participants | 3 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 237 Participants | 36 Participants | 28 Participants | 30 Participants | 38 Participants | 38 Participants | 31 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 239 Participants | 35 Participants | 32 Participants | 27 Participants | 38 Participants | 39 Participants | 34 Participants | 34 Participants |
| Sex: Female, Male Female | 159 Participants | 19 Participants | 22 Participants | 18 Participants | 29 Participants | 23 Participants | 21 Participants | 27 Participants |
| Sex: Female, Male Male | 107 Participants | 19 Participants | 13 Participants | 15 Participants | 11 Participants | 19 Participants | 18 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 1 / 39 | 1 / 42 | 0 / 40 | 0 / 33 | 0 / 36 | 0 / 37 | 0 / 31 | 0 / 32 | 0 / 33 |
| other Total, other adverse events | 20 / 39 | 27 / 39 | 26 / 42 | 22 / 40 | 18 / 33 | 23 / 36 | 24 / 37 | 19 / 31 | 22 / 32 | 24 / 33 |
| serious Total, serious adverse events | 3 / 39 | 2 / 39 | 4 / 42 | 4 / 40 | 1 / 33 | 2 / 36 | 6 / 37 | 4 / 31 | 3 / 32 | 2 / 33 |
Outcome results
Primary
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand)
Time frame: Baseline and Week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand) | 8.8 Percent Change | Standard Error 6.4 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand) | -29.7 Percent Change | Standard Error 6.4 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand) | -44.0 Percent Change | Standard Error 6.3 |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand) | -47.2 Percent Change | Standard Error 6.2 |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand) | 0.6 Percent Change | Standard Error 6.6 |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand) | -23.5 Percent Change | Standard Error 6.6 |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand) | -49.9 Percent Change | Standard Error 6.1 |
p-value: <0.000195% CI: [-56.5, -20.6]Mixed Models Analysis
p-value: <0.000195% CI: [-70.7, -35.1]Mixed Models Analysis
p-value: <0.000195% CI: [-73.7, -38.3]Mixed Models Analysis
p-value: =0.010995% CI: [-42.6, -5.7]Mixed Models Analysis
p-value: <0.000195% CI: [-68.4, -32.6]Mixed Models Analysis
Secondary
Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)
Time frame: Week 16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 11.3 Percentage of Participants |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 68.1 Percentage of Participants |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 73.9 Percentage of Participants |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 71.4 Percentage of Participants |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 15.5 Percentage of Participants |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 57.9 Percentage of Participants |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 86.8 Percentage of Participants |
p-value: <0.000195% CI: [5.1, 72.8]Regression, Logistic
p-value: <0.000195% CI: [6.4, 89.2]Regression, Logistic
p-value: <0.000195% CI: [6, 80.5]Regression, Logistic
p-value: =0.000795% CI: [2.5, 29.2]Regression, Logistic
p-value: <0.000195% CI: [10.4, 172.3]Regression, Logistic
Secondary
Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)
Time frame: Week 16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 5.2 Percentage of Participants |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 28.6 Percentage of Participants |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 53.7 Percentage of Participants |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 60.6 Percentage of Participants |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 12.3 Percentage of Participants |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 24.6 Percentage of Participants |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand) | 63.2 Percentage of Participants |
p-value: =0.0195% CI: [1.7, 53.5]Regression, Logistic
p-value: =0.000195% CI: [4.7, 129.9]Regression, Logistic
p-value: <0.000195% CI: [6.7, 194.7]Regression, Logistic
p-value: =0.318595% CI: [0.5, 8.2]Regression, Logistic
p-value: <0.000195% CI: [3.9, 54.2]Regression, Logistic
Secondary
Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand)
Percentage of Participants with Calculated LDL-C \< 50 milligrams/deciliter (mg/dL) \[1.30 Millimoles per liter (mmol/L)\] at Week 16 (ITT Estimand)
Time frame: Week 16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand) | 5.1 Percentage of Participants |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand) | 22.8 Percentage of Participants |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand) | 29.7 Percentage of Participants |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand) | 40.8 Percentage of Participants |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand) | 9.3 Percentage of Participants |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand) | 13.2 Percentage of Participants |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand) | 39.5 Percentage of Participants |
p-value: =0.071895% CI: [0.9, 26.5]Regression, Logistic
p-value: =0.004895% CI: [2.1, 62.1]Regression, Logistic
p-value: =0.001595% CI: [2.8, 76.8]Regression, Logistic
p-value: =0.52795% CI: [0.3, 8.4]Regression, Logistic
p-value: =0.004795% CI: [1.9, 31.7]Regression, Logistic
Secondary
Percent Change From Baseline in Apo B at Week 24 (ITT Estimand)
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Apo B at Week 24 (ITT Estimand) | 5.9 Percent Change | Standard Error 6 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Apo B at Week 24 (ITT Estimand) | -15.9 Percent Change | Standard Error 5.9 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Apo B at Week 24 (ITT Estimand) | -34.5 Percent Change | Standard Error 5.6 |
p-value: =0.011195% CI: [-38.4, -5.1]Mixed Models Analysis
p-value: <0.000195% CI: [-56.7, -24]Mixed Models Analysis
Secondary
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand)
Time frame: Baseline and Week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand) | 6.7 Percent Change | Standard Error 5.1 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand) | -19.9 Percent Change | Standard Error 5.1 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand) | -35.2 Percent Change | Standard Error 5.1 |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand) | -38.8 Percent Change | Standard Error 4.9 |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand) | -3.8 Percent Change | Standard Error 4.7 |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand) | -20.4 Percent Change | Standard Error 4.6 |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand) | -43.2 Percent Change | Standard Error 4.3 |
p-value: =0.000395% CI: [-40.9, -12.4]Mixed Models Analysis
p-value: <0.000195% CI: [-56.1, -27.9]Mixed Models Analysis
p-value: <0.000195% CI: [-59.5, -31.5]Mixed Models Analysis
p-value: =0.013295% CI: [-29.7, -3.5]Mixed Models Analysis
p-value: <0.000195% CI: [-52, -26.8]Mixed Models Analysis
Secondary
Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand)
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand) | 14.8 Percent Change | Standard Error 8.3 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand) | -17.7 Percent Change | Standard Error 8 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand) | -39.7 Percent Change | Standard Error 7.7 |
p-value: =0.005995% CI: [-55.5, -9.6]Mixed Models Analysis
p-value: <0.000195% CI: [-77, -32]Mixed Models Analysis
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand)
Time frame: Baseline and Week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand) | 8.1 Percent Change | Standard Error 4.5 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand) | -38.0 Percent Change | Standard Error 4.2 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand) | -47.7 Percent Change | Standard Error 4 |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand) | -53.4 Percent Change | Standard Error 3.9 |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand) | -6.9 Percent Change | Standard Error 4.7 |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand) | -32.1 Percent Change | Standard Error 4.5 |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand) | -52.8 Percent Change | Standard Error 4.1 |
p-value: <0.000195% CI: [-57.8, -34.3]Regression, Linear
p-value: <0.000195% CI: [-67.3, -44.3]Regression, Linear
p-value: <0.000195% CI: [-72.9, -50]Regression, Linear
p-value: =0.000195% CI: [-38, -12.4]Regression, Linear
p-value: <0.000195% CI: [-58.4, -33.5]Regression, Linear
Secondary
Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand)
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand) | -6.1 Percent Change | Standard Error 5.4 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand) | -23.2 Percent Change | Standard Error 5.1 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand) | -51.3 Percent Change | Standard Error 4.8 |
p-value: =0.022895% CI: [-31.8, -2.4]Regression, Linear
p-value: <0.000195% CI: [-59.6, -31]Regression, Linear
Secondary
Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand)
Time frame: Baseline and Week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand) | 0.3 Percent Change | Standard Error 3.9 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand) | -10.3 Percent Change | Standard Error 4.1 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand) | -11.6 Percent Change | Standard Error 4 |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand) | -8.9 Percent Change | Standard Error 4 |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand) | 0.8 Percent Change | Standard Error 3.7 |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand) | -15.7 Percent Change | Standard Error 3.7 |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand) | -15.7 Percent Change | Standard Error 3.3 |
p-value: =0.063595% CI: [-21.8, 0.6]Regression, Linear
p-value: =0.031495% CI: [-22.8, -1.1]Regression, Linear
p-value: =0.092395% CI: [-19.9, 1.5]Regression, Linear
p-value: =0.001795% CI: [-26.8, -6.2]Regression, Linear
p-value: =0.000995% CI: [-26.2, -6.8]Regression, Linear
Secondary
Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand)
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand) | -1.4 Percent Change | Standard Error 4.1 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand) | -17.5 Percent Change | Standard Error 4 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand) | -16.0 Percent Change | Standard Error 3.7 |
p-value: =0.005495% CI: [-27.4, -4.7]Regression, Linear
p-value: =0.008595% CI: [-25.4, -3.7]Regression, Linear
Secondary
Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand)
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand) | 10.4 Percent Change | Standard Error 7 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand) | -20.2 Percent Change | Standard Error 6.7 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand) | -44.3 Percent Change | Standard Error 6.4 |
p-value: =0.002195% CI: [-49.8, -11.4]Mixed Models Analysis
p-value: <0.000195% CI: [-73.4, -35.8]Mixed Models Analysis
Secondary
Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand)
Time frame: Baseline and Week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand) | 8.0 Percent Change | Standard Error 5.4 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand) | -31.3 Percent Change | Standard Error 5.4 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand) | -45.8 Percent Change | Standard Error 5.3 |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand) | -50.6 Percent Change | Standard Error 5.2 |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand) | -1.1 Percent Change | Standard Error 5.8 |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand) | -24.8 Percent Change | Standard Error 5.7 |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand) | -52.0 Percent Change | Standard Error 5.3 |
p-value: <0.000195% CI: [-54.4, -24.3]Mixed Models Analysis
p-value: <0.000195% CI: [-68.8, -38.9]Mixed Models Analysis
p-value: <0.000195% CI: [-73.4, -43.7]Mixed Models Analysis
p-value: =0.004295% CI: [-39.7, -7.7]Mixed Models Analysis
p-value: <0.000195% CI: [-66.4, -35.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand)
Time frame: Baseline and Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand) | 8.5 Percent Change | Standard Error 5.1 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand) | -19.9 Percent Change | Standard Error 4.9 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand) | -40.8 Percent Change | Standard Error 4.7 |
p-value: =0.000195% CI: [-42.6, -14.3]Mixed Models Analysis
p-value: <0.000195% CI: [-63.2, -35.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand)
Time frame: Baseline and Week 16
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo SC QW (DBTP) | Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand) | 6.1 Percent Change | Standard Error 4 |
| Group A: Evinacumab 300 mg SC Q2W (DBTP) | Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand) | -31.0 Percent Change | Standard Error 4 |
| Group A: Evinacumab 300 mg SC QW (DBTP) | Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand) | -40.3 Percent Change | Standard Error 4 |
| Group A: Evinacumab 450 mg SC QW (DBTP) | Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand) | -45.4 Percent Change | Standard Error 3.9 |
| Group B: Placebo IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand) | -0.4 Percent Change | Standard Error 4.5 |
| Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand) | -22.6 Percent Change | Standard Error 4.4 |
| Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP) | Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand) | -46.8 Percent Change | Standard Error 4.1 |
p-value: <0.000195% CI: [-48.4, -25.8]Mixed Models Analysis
p-value: <0.000195% CI: [-57.5, -35.2]Mixed Models Analysis
p-value: <0.000195% CI: [-62.5, -40.4]Mixed Models Analysis
p-value: =0.000695% CI: [-34.6, -9.8]Mixed Models Analysis
p-value: <0.000195% CI: [-58.4, -34.4]Mixed Models Analysis