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

Regeneron Pharmaceuticals77 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Hypercholesterolemia

Interventions

AlirocumabDRUG

Alirocumab two SC injections in the abdomen only.

PlaceboDRUG

Placebo two SC injections in the abdomen only.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Must meet the World Health Organization criteria for heFH 2. Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening 3. Serum LDL-C levels ≥ 100 mg/dL at screening 4. Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit 5. A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential Key Exclusion Criteria: 1. Participants with homozygous FH (clinically or by previous genotyping) 2. 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 3. 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 4. 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) 5. Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit) 6. Fasting serum TG \>350 mg/dL screening 7. LDL apheresis within 12 months before screening

Locations (22)

Unnamed facility

Huntsville, Alabama, United States

Unnamed facility

Mission Viejo, California, United States

Outcomes

Primary Outcomes

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.

Time frame: From Baseline to Week 12 (LOCF)

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: From Baseline to Week 12 (LOCF)

Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis

Data from ClinicalTrials.gov

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Newport Beach, California, United States

Unnamed facility

Bridgeport, Connecticut, United States

Unnamed facility

Jacksonville, Florida, United States

Unnamed facility

Miami, Florida, United States

Unnamed facility

Port Orange, Florida, United States

Unnamed facility

Chicago, Illinois, United States

Unnamed facility

Kansas City, Kansas, United States

Unnamed facility

Auburn, Maine, United States

...and 12 more locations

Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

Time frame: 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..

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: From Baseline to Week 12 (LOCF)