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)

Study Overview
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Brief Summary
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The primary objective of the study was to assess the long-term safety and tolerability of alirocumab in patients with heFH who were receiving concomitant treatment with hydroxymethyl glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), with or without other lipid-modifying therapies (LMTs).

Official Title
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A Phase 2, Open-Label Extension of Study R727-CL-1003 to Evaluate the Long-Term Safety and Efficacy of REGN727 Administered by Subcutaneous Injection in Patients With Heterozygous Familial Hypercholesterolemia

Conditions
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Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: Alirocumab
* Drug: Placebo Matched to Alirocumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Prior participation in and the successful completion of the R727-CL-1003 study (NCT01266876). Patients must be on a stable daily statin regimen for at least 3 weeks before prior to entry into the study A negative urine pregnancy at the screening/baseline visit for women of childbearing potential Key Exclusion Criteria: Reported a drug-related serious adverse event (SAE) or drug-related clinical or laboratory adverse event (AE) in the R727-CL-1003 study that resulted in early termination or withdrawal Significant protocol deviation in R727-CL-1003, such as non-compliance by the investigator or patient Low-density lipoprotein (LDL) apheresis within 12 months before the screening/baseline visit Note: Other exclusion criteria applied

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Matched to Alirocumab<br>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. | Drug: Placebo Matched to Alirocumab<br>* 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<br>|
| Experimental: Alirocumab 150 mg<br>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. | Drug: Alirocumab<br>* 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<br>* Other names: PRALUENT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death | 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. | Baseline (Day 1 of current study) to end of study (Week 218) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to Week 24 | Percent change for serum LDL-C (Low-density lipoprotein cholesterol) from baseline to Week 24 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline (current study) to Week 24 | 
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study to Week 12 | Percent change for serum LDL-C (Low-density lipoprotein cholesterol) from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline (current study) up to Week 12 | 
| Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study to Week 24 | Percent change for Apo B, Non-HDL-C and Total Cholesterol from baseline to Week 24 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline(current study) up to Week 24 | 
| Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol From Baseline in Current Study to Week 12 | Percent change for serum Apo B, Non-HDL-C, and Total Cholesterol from baseline to Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline (current study) up to Week 12 | 
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in Current Study to Week 52 | Percent change for serum LDL-C from baseline to Week 52 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline (current study) up to Week 52 | 
| Percentage of Participants With Low Density Lipoprotein Cholesterol (LDL-C) Less Than (<) 70 Milligrams Per Deciliter (mg/dL) for Prior Myocardial Infarction (MI)/Stroke, or <100 mg/dL [2.59 mmol/L] for Participants Without Prior MI/Stroke at Week 24 | Percentage of participants reaching LDL-C goal (ie, LDL-C <70 mg/dL (1.81 millimoles per liter [mmol/L]) in case of prior MI/stroke, or <100 mg/dL [2.59 mmol/L] for participants without prior MI/stroke) at week 24 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, were reported. | At Week 24 | 
| Percent Change in Lipoprotein a (Lp[a]) at Week 24 | Percent change in serum lipoprotein a at week 24 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported. | At Week 24 | 
| Percent Change in High Density Lipoprotein Cholesterol (HDL-C) at Week 24 and Week 12 | Percent change for serum High Density Lipoprotein Cholesterol (HDL-C) in the current study at weeks 24 and week 12, during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported. | At Week 24 and 12 | 
| Percent Change in Lipoprotein a at Week 12 | Percent change for serum Lipoprotein a at Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported. | At Week 12 | 
| Percent Change in Triglycerides (TG) at Week 24 and Week 12 | Percent change for serum TG at Week 24 and Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported. | At Week 24 and 12 | 
| Percent Change in Apolipoprotein A-1 (Apo A-1) at Week 24 and Week 12 | Percent change for serum Apo A-1 at Week 24 and Week 12 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, was reported. | At Week 24 and Week 12 | 
| Percent Change in Low Density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to the End of Treatment | Percent change for serum LDL-C from baseline to Week 208 during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline (current study) to the End of Treatment (Week 208) | 
| Percentage of Participants With Low Density Lipoprotein Cholesterol (LDL-C) Less Than (<) 70 Milligrams Per Deciliter (mg/dL) for Prior MI/Stroke, or <100 mg/dL [2.59 mmol/L] for Participants Without Prior MI/Stroke at Week 12, 52 and End of Treatment | Percentage of participants reaching LDL-C goal (ie, LDL-C <70 mg/dL (1.81 millimoles per liter [mmol/L]) in case of prior MI/stroke, or <100 mg/dL [2.59 mmol/L] for participants without prior MI/stroke) at week 12, 52 and end of treatment, during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study, were reported. | At Week 12, 52 and End of Treatment (Week 208) | 
| Absolute Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline in the Current Study to Weeks 12, 24, 52, and End of Treatment | Absolute change was reported for serum LDL-C from baseline to weeks 12, 24, 52, and end of Treatment (Week 208) during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline (current study) to Weeks 12, 24, 52, and End of Treatment (Week 208) | 
| Percent Change in Apolipoprotein (Apo) B, Non-High Density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Lipoprotein a (Lp[a]), HDL-C, Triglycerides, and Apolipoprotein A-1 From Baseline in Current Study to Week 52 and End of Treatment | Percent change was reported for serum (Apo B), non-HDL-C, total-C, Lp(a), HDL-C, TG, and Apo A-1 from baseline to weeks 52 and end of treatment (Week 208) during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline (current study) up to Weeks 52 and End of Treatment (Week 208) | 
| Change in Ratio in Apolipoprotein (Apo) B/Apo A-1 From Baseline in Current Study to Week 12, 24, 52, and End of Treatment. | Change in ratio in Apolipoprotein (Apo) B/Apo A-1 from baseline in current Study to week 12, 24, 52, and end of treatment (Week 208) during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | Baseline (current study) to Weeks 12, 24, 52, and End of Treatment (Week 208) | 
| Percentage of Participants With Apolipoprotein (Apo) B <80 mg/dL at Week 12, 24, 52, and End of Treatment | Percentage of participants was calculated with Apo B <80 mg/dL (0.8 mmol/L) at week 12, 24, 52, and End of Treatment (Week 208) during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | At Week 12, 24, 52, and End of Treatment (Week 208) | 
| Percentage of Participants With Non-High Density Lipoprotein Cholesterol (HDL-C) <100 mg/dL (2.59 mmol/L) at Week 12, 24, 52, and End of Treatment | Percentage of participants was calculated with non-HDL-C <100 mg/dL (2.59 mmol/L) at Weeks 12, 24, 52, and End of Treatment (Week 208) during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | At Week 12, 24, 52, and End of Treatment (Week 208) | 
| Percentage of Participants With Low Density Lipoprotein Cholesterol (LDL-C) Less Than (<) 70 Milligrams Per Deciliter (mg/dL) and/or ≥ 50% Reduction in LDL-C (if LDL-C >70 mg/dL [1.81 mmol/L]) at Week 12, 24, 52, and End of Treatment | Percentage of Participants was calculated with LDL-C <70 mg/dL (1.81 mmol/L) and/or ≥ 50% Reduction in LDL-C (if LDL-C >70 mg/dL [1.81 mmol/L]) at Weeks 12, 24, 52, and End of Treatment (Week 208) during the efficacy treatment period, which is defined as the time from the first study drug injection up to 21 days after the last study drug injection in the current study. | At Week 12, 24, 52, and End of Treatment (Week 208) |