Homozygous Familial Hypercholesterolemia
Conditions
Brief summary
The primary objective of the study is to demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) with alirocumab subcutaneous (SC) every 2 weeks (Q2W) in comparison to placebo after 12 weeks of treatment. The secondary objectives of the study are: * To evaluate the effect of alirocumab Q2W on other lipid parameters (ie, apolipoprotein \[Apo\] A-1 and B, non-high-density lipoprotein cholesterol \[non-HDL-C\], total-cholesterol \[TC\], proportion of participants with 15%, 30%, and 50% LDL-C reductions, Lp(a), HDL-C, triglycerides \[TG\]) in participants with HoFH * To evaluate the safety and tolerability of alirocumab SC Q2W in participants with HoFH * To assess the pharmacokinetics of alirocumab SC Q2W in participants with HoFH * To assess the potential development of anti-drug (alirocumab) antibodies
Interventions
DRUGAlirocumab
Alirocumab SC Q2W
DRUGPlacebo
Matching placebo SC Q2W
Sponsors
Sanofi
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 No maximum
Healthy volunteers
No
Inclusion criteria
Note: The information listed below is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial, therefore not all inclusion/
Exclusion criteria
are listed. Key Inclusion Criteria 1. Diagnosis of HoFH by at least 1 of the following genotype or clinical criteria (all patients on LDL apheresis must be diagnosed based on genotype): 1. Documented homozygous or compound heterozygous mutations in both low-density lipoprotein receptor (LDLR) alleles 2. Presence of homozygous or compound heterozygous mutations in Apo B, PCSK9 or LDL receptor adaptor protein 1 (LDLRAP1) 3. Presence of double heterozygous mutations, i.e, mutations on different genes in the LDLR, Apo B or PCSK9 alleles 4. Untreated TC \>500 mg/dL (12.93 mmol/L) and TG \<300 mg/dL (3.39 mmol/L) AND Both parents with history of TC \>250 mg/dL (6.46 mmol/L) OR cutaneous or tendinous xanthoma before age 10 2. Receiving a stable dose of a statin at the screening visit (documentation if statin ineffective or patient unable to tolerate statin) 3. If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior to screening and must have been on a stable weekly (every 7 days) or every other week (every 14 days) schedule or stable settings for at least 8 weeks Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand) | Baseline to Week 12 | The percent change in LDL-C from baseline to week 12 is defined as: 100x (LDL-C value at week 12 - LDL-C value at baseline) / LDL-C value at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12 | Baseline to Week 12 | ITT estimand; The percent change in non-HDL-C from baseline to week 12 is defined as: 100x (non-HDL-C value at week 12 - non-HDL-C value at baseline) / non-HDL-C value at baseline. |
| Percent Change in Total Cholesterol (TC) From Baseline to Week 12 | Baseline to Week 12 | ITT estimand; The percent change in TC from baseline to week 12 is defined as: 100x (TC value at week 12 - TC value at baseline) / TC value at baseline. |
| Percentage of Participants With ≥15% Reduction in LDL-C at Week 12 | At Week 12 | ITT estimand |
| Percentage of Participants With ≥30% Reduction in LDL-C at Week 12 | At Week 12 | ITT estimand |
| Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12 | Baseline to Week 12 | ITT estimand; The percent change in Lp(a) from baseline to week 12 is defined as: 100x (Lp(a) value at week 12 - Lp(a) value at baseline) / Lp(a) value at baseline. |
| Percentage of Participants With ≥50% Reduction in LDL-C at Week 12 | At Week 12 | ITT estimand |
| Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis | Baseline to Week 12 | ITT estimand; The percent change in HDL-C from baseline to week 12 is defined as: 100x (HDL-C value at week 12 - HDL-C value at baseline) / HDL-C value at baseline. |
| Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12 | Baseline to Week 12 | ITT estimand; The percent change in TG from baseline to week 12 is defined as: 100x (TG value at week 12 - TG value at baseline) / TG value at baseline. |
| Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis | Baseline to Week 12 | ITT estimand; The percent change in Apo A-1 from baseline to week 12 is defined as: 100x (Apo A-1 value at week 12 - Apo A-1 value at baseline) / Apo A-1 value at baseline. |
| Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand) | Baseline to Week 12 | Percent change for LDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier. |
| Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand) | Baseline to Week 12 | ITT estimand; The percent change in Apo B from baseline to week 12 is defined as: 100x (Apo B value at week 12 - Apo B value at baseline) / Apo B value at baseline. |
| Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand) | Baseline to Week 12 | Percent change for non-HDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier. |
| Percent Change in TC From Baseline to Week 12 (On-treatment Estimand) | Baseline to Week 12 | Percent change for TC from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier. |
| Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand) | Baseline to Week 12 | Percent change for LP(a) from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier. |
| Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand) | Baseline to Week 12 | Percent change for HDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier. |
| Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand) | Baseline to Week 12 | Percent change for fasting TG from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier. |
| Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand) | Baseline to Week 12 | Percent change for Apo A-1 from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier. |
| Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) | At Week 12 | — |
| Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand) | Baseline to Week 12 | Ratio of Apo B/Apo A1 at week 12 minus ratio of Apo B/Apo A1 at baseline |
| Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time | 26 weeks | — |
| Number of Participants With Adverse Events (AEs) | Baseline to week 32 (End of Study) | All AEs will be recorded from time of informed consent to end of study. Only treatment-emergent adverse events (TEAE) will be reported. Double-blind TEAE observation period is defined as time from first dose of double-blind study drug to last dose of double-blind study drug +70 days, or up to day before first dose of open-label study drug administration, whichever is earlier. Open-label TEAE observation period is defined as time from first open-label study treatment administration to last open-label study treatment administration +70 days. |
| Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand) | Baseline to Week 12 | Percent change for Apo B from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label nvestigational study drug, whichever is earlier. |
Countries
Austria, Canada, Czechia, France, Germany, Greece, Italy, Japan, South Africa, Taiwan, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
Participants were recruited from 27 centers in 13 countries around Europe, Asia, South Africa, and North America. A total of 85 participants were screened. Of those,16 were considered screen failures (mainly due to violations of inclusion/exclusion criteria).
Pre-assignment details
Sixty-nine of the 85 participants were eligible and randomized in a 2:1 ratio to receive either alirocumab 150 mg SC Q2W or matching placebo. Randomization was stratified by LDL apheresis treatment status (on vs off treatment).
Participants by arm
| Arm | Count |
|---|---|
| Placebo in DBTP Participants received matching placebo subcutaneously (SC) every 2 weeks (Q2W) from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W | 24 |
| Alirocumab 150 mg SC Q2W Participants in this arm received alirocumab 150 milligrams (mg) SC Q2W from baseline (Day 1) through Week 10 during the double-blind treatment period. Starting at Week 12, and continuing through Week 22, all participants received open-label alirocumab SC Q2W | 45 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open-Label Treatment Period (OLTP) | Adverse Event | 0 | 2 |
| Open-Label Treatment Period (OLTP) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo in DBTP | Alirocumab 150 mg SC Q2W | Total |
|---|---|---|---|
| Age, Continuous | 45.4 Years STANDARD_DEVIATION 15.8 | 42.3 Years STANDARD_DEVIATION 14.13 | 43.4 Years STANDARD_DEVIATION 14.69 |
| Apo-B/Apo-A1 | 1.590 ratio STANDARD_DEVIATION 1.4746 | 1.635 ratio STANDARD_DEVIATION 0.8693 | 1.619 ratio STANDARD_DEVIATION 1.1067 |
| Apolipoprotein-A1 (Apo-A1) | 124.8 mg/dL STANDARD_DEVIATION 24.59 | 125.6 mg/dL STANDARD_DEVIATION 28.57 | 125.3 mg/dL STANDARD_DEVIATION 27.07 |
| Apolipoprotein-B (Apo-B) | 175.0 mg/dL STANDARD_DEVIATION 95.12 | 193.3 mg/dL STANDARD_DEVIATION 87.59 | 186.9 mg/dL STANDARD_DEVIATION 90.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 43 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting triglycerides (TG) | 111.7 mg/dL STANDARD_DEVIATION 77.97 | 128.0 mg/dL STANDARD_DEVIATION 74.34 | 122.3 mg/dL STANDARD_DEVIATION 75.45 |
| High-density lipoprotein cholesterol (HDL-C) | 43.2 mg/dL STANDARD_DEVIATION 11.96 | 43.8 mg/dL STANDARD_DEVIATION 14.78 | 43.6 mg/dL STANDARD_DEVIATION 13.78 |
| Lipoprotein(a) [Lp(a)] | 40.0 mg/dL STANDARD_DEVIATION 36.41 | 42.9 mg/dL STANDARD_DEVIATION 36.34 | 41.9 mg/dL STANDARD_DEVIATION 36.12 |
| Low-density lipoprotein cholesterol (LDL-C) | 259.6 milligram/deciLiter (mg/dL) STANDARD_DEVIATION 175.75 | 295.0 milligram/deciLiter (mg/dL) STANDARD_DEVIATION 154.59 | 282.7 milligram/deciLiter (mg/dL) STANDARD_DEVIATION 161.86 |
| Non-high-density lipoprotein cholesterol (Non-HDL-C) | 282.0 mg/dL STANDARD_DEVIATION 177.41 | 320.5 mg/dL STANDARD_DEVIATION 160.36 | 307.1 mg/dL STANDARD_DEVIATION 166.22 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 36 Participants | 54 Participants |
| Sex: Female, Male Female | 11 Participants | 24 Participants | 35 Participants |
| Sex: Female, Male Male | 13 Participants | 21 Participants | 34 Participants |
| Total-cholesterol (Total-C) | 325.1 mg/dL STANDARD_DEVIATION 171.57 | 364.3 mg/dL STANDARD_DEVIATION 157.3 | 350.7 mg/dL STANDARD_DEVIATION 162.24 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 45 | 0 / 24 | 0 / 45 |
| other Total, other adverse events | 4 / 24 | 8 / 45 | 2 / 24 | 4 / 45 |
| serious Total, serious adverse events | 0 / 24 | 0 / 45 | 0 / 24 | 1 / 45 |
Outcome results
Primary
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand)
The percent change in LDL-C from baseline to week 12 is defined as: 100x (LDL-C value at week 12 - LDL-C value at baseline) / LDL-C value at baseline.
Time frame: Baseline to Week 12
Population: ITT estimand (All randomized participants who had at least 1 measurement value for LDL-C before the first dose of double blind investigational study drug)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand) | 8.6 Percentage of change | Standard Error 6.3 |
| Alirocumab 150 mg SC Q2W | Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand) | -26.9 Percentage of change | Standard Error 4.6 |
p-value: <0.000195% CI: [-51.2, -19.9]MMRM
Secondary
Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand)
Ratio of Apo B/Apo A1 at week 12 minus ratio of Apo B/Apo A1 at baseline
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand) | 0.0 Ratio of change | Standard Error 0.1 |
| Alirocumab 150 mg SC Q2W | Absolute Change in the Ratio of Apo B/Apo A-1 From Baseline to Week 12 (ITT Estimand) | -0.3 Ratio of change | Standard Error 0.1 |
95% CI: [-0.6, -0.1]
Secondary
Number of Participants With Adverse Events (AEs)
All AEs will be recorded from time of informed consent to end of study. Only treatment-emergent adverse events (TEAE) will be reported. Double-blind TEAE observation period is defined as time from first dose of double-blind study drug to last dose of double-blind study drug +70 days, or up to day before first dose of open-label study drug administration, whichever is earlier. Open-label TEAE observation period is defined as time from first open-label study treatment administration to last open-label study treatment administration +70 days.
Time frame: Baseline to week 32 (End of Study)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo in DBTP | Number of Participants With Adverse Events (AEs) | Participants with any TEAE | 12 Participants |
| Placebo in DBTP | Number of Participants With Adverse Events (AEs) | Participants with TEAE Serious Adverse Event (SAE) | 0 Participants |
| Alirocumab 150 mg SC Q2W | Number of Participants With Adverse Events (AEs) | Participants with any TEAE | 20 Participants |
| Alirocumab 150 mg SC Q2W | Number of Participants With Adverse Events (AEs) | Participants with TEAE Serious Adverse Event (SAE) | 0 Participants |
| Alirocumab 150 mg SC Q2W in OLTP | Number of Participants With Adverse Events (AEs) | Participants with any TEAE | 24 Participants |
| Alirocumab 150 mg SC Q2W in OLTP | Number of Participants With Adverse Events (AEs) | Participants with TEAE Serious Adverse Event (SAE) | 1 Participants |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time
Time frame: 26 weeks
Population: Here 'n' = number of evaluable participants at this time point
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo in DBTP | Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time | 1 Participants |
| Alirocumab 150 mg SC Q2W | Number of Participants With Anti-Drug Antibodies (ADA) to REGN727 Over Time | 1 Participants |
Secondary
Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand)
Time frame: At Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo in DBTP | Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) | ≥ 15% | 12.5 Percentage of participants |
| Placebo in DBTP | Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) | ≥ 30% | 4.2 Percentage of participants |
| Placebo in DBTP | Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) | ≥ 50% | 0 Percentage of participants |
| Alirocumab 150 mg SC Q2W | Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) | ≥ 15% | 61.9 Percentage of participants |
| Alirocumab 150 mg SC Q2W | Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) | ≥ 30% | 57.1 Percentage of participants |
| Alirocumab 150 mg SC Q2W | Percentage of Participants With ≥15% Reduction, ≥30% Reduction, and ≥50% Reduction in LDL-C at Week 12 (On-treatment Estimand) | ≥ 50% | 26.7 Percentage of participants |
Comparison: ≥15% reduction95% CI: [3.1, 48.8]
95% CI: [4.3, 308.9]
Comparison: ≥ 50% reduction
Secondary
Percentage of Participants With ≥15% Reduction in LDL-C at Week 12
ITT estimand
Time frame: At Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo in DBTP | Percentage of Participants With ≥15% Reduction in LDL-C at Week 12 | 12.5 Percentage of participants |
| Alirocumab 150 mg SC Q2W | Percentage of Participants With ≥15% Reduction in LDL-C at Week 12 | 61.9 Percentage of participants |
p-value: =0.000495% CI: [3.1, 48.8]Regression, Logistic
Secondary
Percentage of Participants With ≥30% Reduction in LDL-C at Week 12
ITT estimand
Time frame: At Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo in DBTP | Percentage of Participants With ≥30% Reduction in LDL-C at Week 12 | 4.2 Percentage of participants |
| Alirocumab 150 mg SC Q2W | Percentage of Participants With ≥30% Reduction in LDL-C at Week 12 | 57.1 Percentage of participants |
p-value: =0.00195% CI: [4.3, 308.9]Regression, Logistic
Secondary
Percentage of Participants With ≥50% Reduction in LDL-C at Week 12
ITT estimand
Time frame: At Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo in DBTP | Percentage of Participants With ≥50% Reduction in LDL-C at Week 12 | 0 Percentage of participants |
| Alirocumab 150 mg SC Q2W | Percentage of Participants With ≥50% Reduction in LDL-C at Week 12 | 26.7 Percentage of participants |
p-value: =0.0017Exact Conditional Logistic Regression
Secondary
Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis
ITT estimand; The percent change in Apo A-1 from baseline to week 12 is defined as: 100x (Apo A-1 value at week 12 - Apo A-1 value at baseline) / Apo A-1 value at baseline.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis | 1.4 Percentage of change | Standard Error 2.9 |
| Alirocumab 150 mg SC Q2W | Percent Change in Apo A-1 From Baseline to Week 12 -- ITT Analysis | 5.0 Percentage of change | Standard Error 2.1 |
95% CI: [-3.6, 10.7]
Secondary
Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand)
Percent change for Apo A-1 from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand) | 1.4 Percentage of change | Standard Error 2.9 |
| Alirocumab 150 mg SC Q2W | Percent Change in Apo A-1 From Baseline to Week 12 (On-treatment Estimand) | 5.0 Percentage of change | Standard Error 2.1 |
95% CI: [-3.6, 10.7]
Secondary
Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand)
Percent change for Apo B from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label nvestigational study drug, whichever is earlier.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand) | 7.2 Percentage of change | Standard Error 5 |
| Alirocumab 150 mg SC Q2W | Percent Change in Apo B From Baseline to Week 12 (On-treatment Estimand) | -22.5 Percentage of change | Standard Error 3.7 |
95% CI: [-43.3, -17.3]
Secondary
Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand)
ITT estimand; The percent change in Apo B from baseline to week 12 is defined as: 100x (Apo B value at week 12 - Apo B value at baseline) / Apo B value at baseline.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand) | 7.2 Percentage of change | Standard Error 5 |
| Alirocumab 150 mg SC Q2W | Percent Change in Apolipoprotein (Apo) B From Baseline to Week 12 (ITT Estimand) | -22.5 Percentage of change | Standard Error 3.7 |
p-value: <0.000195% CI: [-42.3, -17.3]MMRM
Secondary
Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand)
Percent change for fasting TG from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand) | 3.9 Percentage of change | Standard Error 5.7 |
| Alirocumab 150 mg SC Q2W | Percent Change in Fasting TG From Baseline to Week 12 (On-treatment Estimand) | -7.4 Percentage of change | Standard Error 4.2 |
95% CI: [-25.2, 2.6]
Secondary
Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12
ITT estimand; The percent change in TG from baseline to week 12 is defined as: 100x (TG value at week 12 - TG value at baseline) / TG value at baseline.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12 | 3.9 Percentage of change | Standard Error 5.7 |
| Alirocumab 150 mg SC Q2W | Percent Change in Fasting Triglycerides (TG) From Baseline to Week 12 | -7.4 Percentage of change | Standard Error 4.2 |
95% CI: [-25.2, 2.6]
Secondary
Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis
ITT estimand; The percent change in HDL-C from baseline to week 12 is defined as: 100x (HDL-C value at week 12 - HDL-C value at baseline) / HDL-C value at baseline.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis | 2.7 Percentage of change | Standard Error 3.1 |
| Alirocumab 150 mg SC Q2W | Percent Change in HDL-C From Baseline to Week 12 - ITT Analysis | 6.3 Percentage of change | Standard Error 2.3 |
p-value: =0.354195% CI: [-4.1, 11.3]MMRM
Secondary
Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand)
Percent change for HDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand) | 2.7 Percentage of change | Standard Error 3.1 |
| Alirocumab 150 mg SC Q2W | Percent Change in HDL-C From Baseline to Week 12 (On-treatment Estimand) | 6.3 Percentage of change | Standard Error 2.3 |
95% CI: [-4.1, 11.3]
Secondary
Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand)
Percent change for LDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand) | 8.6 Percentage of change | Standard Error 6.3 |
| Alirocumab 150 mg SC Q2W | Percent Change in LDL-C From Baseline to Week 12 (On-treatment Estimand) | -26.9 Percentage of change | Standard Error 4.6 |
95% CI: [-51.2, -19.9]
Secondary
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12
ITT estimand; The percent change in Lp(a) from baseline to week 12 is defined as: 100x (Lp(a) value at week 12 - Lp(a) value at baseline) / Lp(a) value at baseline.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12 | 8.8 Percentage of change | Standard Error 5.4 |
| Alirocumab 150 mg SC Q2W | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Week 12 | -19.6 Percentage of change | Standard Error 4 |
p-value: <0.000195% CI: [-41.5, -15.2]Regression model
Secondary
Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand)
Percent change for LP(a) from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand) | 8.8 Percentage of change | Standard Error 5.4 |
| Alirocumab 150 mg SC Q2W | Percent Change in Lp(a) From Baseline to Week 12 (On-treatment Estimand) | -19.6 Percentage of change | Standard Error 4 |
95% CI: [-41.5, -15.2]
Secondary
Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand)
Percent change for non-HDL-C from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand) | 8.0 Percentage of change | Standard Error 5.9 |
| Alirocumab 150 mg SC Q2W | Percent Change in Non-HDL-C From Baseline to Week 12 (On-treatment Estimand) | -24.8 Percentage of change | Standard Error 4.3 |
95% CI: [-47.6, -18.2]
Secondary
Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12
ITT estimand; The percent change in non-HDL-C from baseline to week 12 is defined as: 100x (non-HDL-C value at week 12 - non-HDL-C value at baseline) / non-HDL-C value at baseline.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12 | 8.0 Percentage of change | Standard Error 5.9 |
| Alirocumab 150 mg SC Q2W | Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12 | -24.8 Percentage of change | Standard Error 4.3 |
p-value: <0.000195% CI: [-47.6, -18.2]MMRM
Secondary
Percent Change in TC From Baseline to Week 12 (On-treatment Estimand)
Percent change for TC from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first double-blind investigational study drug injection up to 21 days after the last double-blind investigational study drug injection, or the first dose of the open-label investigational study drug, whichever is earlier.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in TC From Baseline to Week 12 (On-treatment Estimand) | 6.6 Percentage of change | Standard Error 5 |
| Alirocumab 150 mg SC Q2W | Percent Change in TC From Baseline to Week 12 (On-treatment Estimand) | -19.8 Percentage of change | Standard Error 3.7 |
95% CI: [-28.9, -14]
Secondary
Percent Change in Total Cholesterol (TC) From Baseline to Week 12
ITT estimand; The percent change in TC from baseline to week 12 is defined as: 100x (TC value at week 12 - TC value at baseline) / TC value at baseline.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo in DBTP | Percent Change in Total Cholesterol (TC) From Baseline to Week 12 | 6.6 Percentage of change | Standard Error 5 |
| Alirocumab 150 mg SC Q2W | Percent Change in Total Cholesterol (TC) From Baseline to Week 12 | -19.8 Percentage of change | Standard Error 3.7 |
p-value: <0.000195% CI: [-38.9, -14]MMRM