Open Label Study of Long Term Safety Evaluation of Alirocumab

Study Overview
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Brief Summary
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Primary Objective: To assess the long-term safety of alirocumab (SAR236553/REGN727) when added to lipid-lowering therapy in participants with heterozygous familial hypercholesterolemia (heFH) who had completed EFC12492 (NCT01623115), R727-CL-1112 (NCT01709500), EFC12732 (NCT01617655) and LTS11717 (NCT01507831). Secondary Objectives: To evaluate the long-term efficacy of alirocumab on lipid parameters. To evaluate the long-term immunogenicity of alirocumab.

Detailed Description
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The maximum study duration will be 176 weeks per participant.

Official Title
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Open-Label Extension Study of EFC12492, R727-CL-1112, EFC12732 and LTS11717 Studies to Assess the Long-Term Safety and Efficacy of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: Alirocumab
* Drug: Lipid-Modifying Therapy (LMT)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants with heFH who had completed one of the four parent studies (EFC12492, R727-CL-1112, EFC12732 and LTS11717). Exclusion criteria: Significant protocol deviation in the parent study; Any permanent treatment discontinuation from the parent study. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alirocumab 75 or 150 mg Q2W<br>Alirocumab 75 mg or 150 mg every 2 weeks (Q2W) added to stable lipid-modifying therapy (LMT) for up to 168 additional weeks (or until the product was commercially available) in participants who completed the parent studies EFC12492, R727-CL-1112, EFC12732 and LTS11717. | Drug: Alirocumab<br>* Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a pre-filled syringe.<br>* Other names: Praluent;Drug: Lipid-Modifying Therapy (LMT)<br>* Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced Adverse Events (AEs) | Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of alirocumab in this study up to the last dose of alirocumab received in this study +70 days). Clinically significant lab and vital sign abnormalities were to be reported as AEs. | Up to 10 weeks after last study drug administration (maximum of 176 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Calculated LDL-C at Weeks 8, 24, 48, 72, 96, 120, 144 and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) Over Time | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) Over Time | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Percentage of Participants With Calculated LDL-C <70 mg/dL (1.81mmol/L) and/or >=50% Reduction in Calculated LDL-C From Baseline (if Calculated LDL-C >=70 mg/dL [1.81mmol/L]) Over Time | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Percent Change From Baseline in Total-cholesterol at Weeks 8, 24, 48, 72, 96, 120, 144 and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Percent Change From Baseline in Fasting Triglycerides (TGs) at Weeks 8, 24, 48, 72, 96, 120, 144 and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, and 168 | 
| Percent Change From Baseline in Lipoprotein (a) at Weeks 48, 96, 144 and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 48, 96, 144, and 168 | 
| Percent Change From Baseline in Apolipoprotein-B (Apo-B) at Weeks 48, 96, 144, and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 48, 96, 144, and 168 | 
| Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Weeks 48, 96, 144, and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 48, 96, 144, and 168 | 
| Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 48, 96, 144, and 168 | Baseline here corresponds to the baseline in the parent study (EFC12492, R727-CL-1112, EFC12732 or LTS11717). Post-baseline on-treatment data was obtained from Week 8 onwards up to Week 168 in this study. | Parent Baseline, Weeks 48, 96, 144, and 168 |