Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01926782 | Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab (REGN727/ SAR236553) in Patients With Primary Hypercholesterolemia (ODYSSEY CHOICE 1) | PHASE3 | COMPLETED | 803 | — | — | Sep 1, 2013 | Apr 1, 2015 | Mar 21, 2017 | 83 | United States, Bulgaria +6 |
| NCT01730053 | Study of Alirocumab (REGN727/SAR236553) added-on to Rosuvastatin Versus Other Lipid Modifying Treatments (LMT) (ODYSSEY OPTIONS II) | PHASE3 | COMPLETED | 305 | — | — | Nov 30, 2012 | May 31, 2014 | Apr 7, 2020 | 93 | United States, Australia +7 |
| NCT01730040 | Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I) | PHASE3 | COMPLETED | 355 | — | — | Oct 1, 2012 | May 1, 2014 | Aug 31, 2015 | 97 | United States, Australia +7 |
| NCT07477704 | A Study to See How Safe and Effective Alirocumab is When Given Weekly to Adult Participants Who Have Hypercholesterolemia | PHASE2 | NOT YET_RECRUITING | 420 | — | — | Apr 14, 2026 | Mar 9, 2027 | Mar 17, 2026 | - | — |
| NCT01576484 | Open-Label Extension of Study R727-CL-1003 (NCT01266876) to Evaluate the Long-Term Safety and Efficacy of Alirocumab (REGN727) in Participants With Heterozygous Familial Hypercholesterolemia (HeFH) | PHASE2 | COMPLETED | 58 | — | — | Feb 28, 2012 | Dec 22, 2016 | Aug 5, 2020 | 14 | United States, Canada |
| NCT01604824 | A Study of Alirocumab in Participants With Autosomal Dominant Hypercholesterolemia (ADH) and Gain-of-Function Mutations (GOFm) of the Proprotein Convertase Subtilisin Kexin 9 (PCSK9) Gene or Loss-of-Function Mutations (LOFm) of the Apolipoprotein (Apo) B Gene | PHASE2 | COMPLETED | 23 | — | — | Feb 22, 2012 | Jul 28, 2017 | Jun 17, 2020 | 4 | United States, France |
| NCT01266876 | Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia | PHASE2 | COMPLETED | 77 | — | — | Jan 1, 2011 | Nov 1, 2011 | Sep 22, 2015 | 22 | United States, Canada |
Adjusted LS means and standard errors at Week 24 and at averaged Week 21 to 24 from MMRM including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. ITT population (subjects without concomitant statin therapy): all randomized subjects who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Adjusted least squares (LS) means and standard errors at Week 24 and at averaged Week 21 to 24 were obtained from a mixed effect model with repeated measures (MMRM) model to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in this model (ITT analysis). ITT population (subjects with concomitant statin therapy): all randomized subjects who received concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. Alirocumab 75 mg Q2W arm (calibrator arm) was included only to facilitate comparison of results of this study with the results of other studies that used an alirocumab 75 mg Q2W regimen. Hence no statistical comparison was performed for this arm.
Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
An AE was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. Treatment- emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on- treatment period (time from the first dose of study drug to the last dose of study drug plus 70 days). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
By day 15, participants in groups A and C had received 1 subcutaneous (SC) dose of 150 mg alirocumab and participants in group B and D had received 1 SC dose of placebo. \[Baseline adjusted least squares (LS) means and standard errors were obtained using analysis of covariance (ANCOVA) model specifying the treatment arm as the fixed effect and the baseline measured LDL-C value as a covariate.\]
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method.
| Arm | Type | Description |
|---|---|---|
| Placebo Q2W | PLACEBO_COMPARATOR | Two subcutaneous (SC) injections of placebo (for alirocumab) Q2W with or without stable statin therapy for 48 weeks. |
| Alirocumab 75 mg/ Up 150 mg Q2W | EXPERIMENTAL | One SC injection of each Alirocumab 75 mg and placebo Q2W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8. |
| Alirocumab 300 mg/ Up 150 mg Q4W | EXPERIMENTAL | Two SC injections of Alirocumab 150 mg Q4W alternating with two SC injections of placebo Q4W with or without stable statin therapy for 48 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥ 70 mg/dL (1.81 mmol/L) (for very high CV risk participants) or ≥ 100 mg/dL (2.59 mmol/L) (for moderate and high CV risk participants) at Week 8. |
| Rosuvastatin 20 mg | ACTIVE_COMPARATOR | Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received rosuvastatin 20 mg over-encapsulated tablet orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablet orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. |
| Ezetimibe 10 mg + Rosuvastatin 10 mg | ACTIVE_COMPARATOR | Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/up to 150 mg + Rosuvastatin 10 mg | EXPERIMENTAL | Participants, who were receiving rosuvastatin 10 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg SC injection Q2W, rosuvastatin 10 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Rosuvastatin 40 mg | ACTIVE_COMPARATOR | Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received rosuvastatin 40 mg over-encapsulated tablet orally QD, placebo for alirocumab Q2W SC injection, and placebo for ezetimibe QD over-encapsulated tablet orally added to stable LMT for 24 weeks. |
| Ezetimibe 10 mg + Rosuvastatin 20 mg | ACTIVE_COMPARATOR | Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received ezetimibe 10 mg over-encapsulated tablet orally QD, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for alirocumab Q2W SC injection added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/ up to 150 mg + Rosuvastatin 20 mg | EXPERIMENTAL | Participants, who were receiving rosuvastatin 20 mg over-encapsulated tablet orally at baseline, received alirocumab 75 mg Q2W SC injection, rosuvastatin 20 mg over-encapsulated tablet orally QD, and placebo for ezetimibe over-encapsulated tablet orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Atorvastatin 40 mg | ACTIVE_COMPARATOR | Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks. |
| Ezetimibe 10 mg + Atorvastatin 20 mg | ACTIVE_COMPARATOR | Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg | EXPERIMENTAL | Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Atorvastatin 80 mg | ACTIVE_COMPARATOR | Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. |
| Ezetimibe 10 mg + Atorvastatin 40 mg | ACTIVE_COMPARATOR | Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks. |
| Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg | EXPERIMENTAL | Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history. |
| Arm 1 - Low Dose | EXPERIMENTAL | - |
| Arm 2 - Medium Dose | EXPERIMENTAL | - |
| Arm 3 - High Dose | EXPERIMENTAL | - |
| Arm 4 - Higher Dose | EXPERIMENTAL | - |
| Placebo Matched to Alirocumab | PLACEBO_COMPARATOR | Participants who received placebo in parent study (NCT01576484), has received a subcutaneous injection of placebo matched to alirocumab every 2 weeks for 4 years in this study. |
| Alirocumab 150 mg | EXPERIMENTAL | Participants who received alirocumab in parent study (NCT01576484), has received a subcutaneous injection of alirocumab 150 milligram (mg) every 2 weeks for 4 years in this study. |
| GOFm PCSK9 (Cohort 1): Alirocumab From Day 1 | EXPERIMENTAL | Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group A). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years. |
| GOFm PCSK9 (Cohort 1): Alirocumab From Day 15 | EXPERIMENTAL | Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 (\[matching placebo at Week 0 (Day 1), 10 and 14\]) during the double-blind period (Group B). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years. |
| GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1 | EXPERIMENTAL | Participants with gain-of-function mutation (GOFm) in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in the apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group C). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years. |
| GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15 | EXPERIMENTAL | Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 (\[matching placebo at Week 0 (Day 1), 10 and 14\]) during the double-blind period (Group D). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years. |
| Placebo | PLACEBO_COMPARATOR | Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab 150 mg Q4W | EXPERIMENTAL | Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab 200 mg Q4W | EXPERIMENTAL | Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab 300 mg Q4W | EXPERIMENTAL | Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Alirocumab 150 mg Q2W | EXPERIMENTAL | Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. |
| Name | Type | Description |
|---|---|---|
| Placebo (for alirocumab) | DRUG | Solution for injection, subcutaneous injections in the abdomen, thigh, or outer area of upper arm with an auto-injector. |
| Alirocumab | DRUG | Solution for injection, subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector. |
| Statin | DRUG | Atorvastatin, rosuvastatin and simvastatin at stable dose in participants with stable statin therapy |
| Rosuvastatin | DRUG | Rosuvastatin over-encapsulated tablets orally. |
| Ezetimibe | DRUG | Ezetimibe over-encapsulated tablets orally. |
| Placebo | DRUG | Placebo for alirocumab and ezetimibe. |
| Atorvastatin | DRUG | Atorvastatin over-encapsulated tablets orally. |
| Placebo Matched to Alirocumab | DRUG | Placebo matched to alirocumab was supplied in a pre-filled syringe and administered subcutaneously (SC) in the abdomen, thigh, or outer upper arm; REGN727(SAR236553) is an anti-PCSK9 (proprotein convertase subtilisin/kexin type 9) antibody |
Inclusion Criteria: 1. Men and women \> age 18 or legal age of majority with elevated LDL-C 2. Patients not having adequate control of their hypercholesterolemia based on their individual level of CVD risk 3. Willing and able to comply with clinic visits and study-related procedures 4. Provided sig...