Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of REGN727/SAR236553 in participants diagnosed with heterozygous familial hypercholesterolemia (heFH)

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, 12-Week Study of the Safety and Efficacy of REGN727 in Patients With Heterozygous Familial Hypercholesterolemia

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: Alirocumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must meet the World Health Organization criteria for heFH Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening Serum LDL-C levels ≥ 100 mg/dL at screening Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential Key Exclusion Criteria: Participants with homozygous FH (clinically or by previous genotyping) Use of a medication (other than a statin or EZE) to alter serum lipids within 42 days (6 weeks) before screening including, but not limited to: Fibrates Niacin (>500 mg/day) Omega-3 fatty acids (>1000 mg/day of DHA/EPA) Bile acid resins Use of nutraceuticals or OTC medications that may alter lipid levels that are not stable for at least 6 weeks before screening and are not planned to remain constant throughout the study. Examples include: Omega-3 fatty acids (≤1000 mg/day of DHA/EPA) Niacin (≤500 mg/day) Plant stanols, such as found in Benecol, flax seed oil, psyllium Red yeast rice Disorders known to influence lipid levels, such as nephrotic syndrome, significant liver disease, Cushing's disease, untreated hypothyroidism (patients on stable thyroid replacement for at least 12 weeks before the full screening visit, who are metabolically euthyroid by thyroid-stimulating hormone (TSH) testing are allowed) Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit) Fasting serum TG >350 mg/dL screening LDL apheresis within 12 months before screening

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | Drug: Placebo<br>* Placebo two SC injections in the abdomen only.<br>|
| Experimental: Alirocumab 150 mg Q4W<br>Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | Drug: Alirocumab<br>* Alirocumab two SC injections in the abdomen only.<br>* Other names: REGN727/SAR236553;|
| Experimental: Alirocumab 200 mg Q4W<br>Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | Drug: Alirocumab<br>* Alirocumab two SC injections in the abdomen only.<br>* Other names: REGN727/SAR236553;|
| Experimental: Alirocumab 300 mg Q4W<br>Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | Drug: Alirocumab<br>* Alirocumab two SC injections in the abdomen only.<br>* Other names: REGN727/SAR236553;|
| Experimental: Alirocumab 150 mg Q2W<br>Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks. | Drug: Alirocumab<br>* Alirocumab two SC injections in the abdomen only.<br>* Other names: REGN727/SAR236553;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | 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. | From Baseline to Week 12 (LOCF) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis | Calculated LDL-C value was obtained from Friedewald formula. Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 (LOCF) | 
| Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis | Calculated LDL-C value was obtained from Friedewald formula. | Week 12 (LOCF) | 
| Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis | Calculated LDL-C value was obtained from Friedewald formula. | Week 12 (LOCF) | 
| Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 (LOCF) | 
| Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 (LOCF) | 
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.. | From Baseline to Week 12 (LOCF) | 
| Absolute Change From Baseline in HDL-C at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 (LOCF) | 
| Percent Change From Baseline in Triglycerides at Week 12 - On-treatment Analysis | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range) | From Baseline to Week 12 (LOCF) | 
| Absolute Change From Baseline in Triglycerides at Week at 12 - On-treatment Analysis | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range) | From Baseline to Week 12 (LOCF) | 
| Percent Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 | 
| Absolute Change From Baseline in Non-HDL-C at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 (LOCF) | 
| Percent Change From Baseline in Apo Lipoprotein B (Apo-B) at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 (LOCF) | 
| Absolute Change From Baseline in Apo-B at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 | 
| Percent Change From Baseline in Apolipoprotein - A1 (Apo-A1) at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 (LOCF) | 
| Absolute Change From Baseline in Apo-A1 at Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 (LOCF) | 
| Absolute Change in the Ratio ApoB/ApoA-1 From Baseline to Week 12 - On-treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | From Baseline to Week 12 | 
| Percent Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range) | From Baseline to Week 12 (LOCF) | 
| Absolute Change From Baseline in Lipoprotein(a) at Week 12 - On-treatment Analysis | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameter, percent changes were expressed as median (interquartile range) | From Baseline to Week 12 (LOCF) |