Study of Alirocumab (REGN727/SAR236553) in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) Undergoing Low-density Lipoprotein (LDL) Apheresis Therapy

Regeneron Pharmaceuticals62 enrolled

Overview

The primary objective of the study is to evaluate the effect of alirocumab 150 mg every 2 weeks (Q2W) in comparison with placebo on the frequency of low-density lipoprotein (LDL) apheresis treatments in participants with heterozygous familial hypercholesterolemia (HeFH) undergoing weekly or bi-weekly LDL apheresis therapy.

LDL apheresis removes low-density lipoproteins (LDL) that transport cholesterol in the plasma portion of the blood. This treatment is mainly used for familial hypercholesterolemia, but can be used in other rare diseases. Familial hypercholesterolemia (HeFH) is an inherited genetic condition that causes accumulation of cholesterol in the blood, which can lead to atherosclerosis and heart disease. This treatment is recommended for patients who do not respond to dietary and/or medication control of LDL cholesterol.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Heterozygous Familial Hypercholesterolemia

Interventions

PlaceboDRUG

AlirocumabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Men and women ≥18 years of age at the time of the screening visit 2. Diagnosis of HeFH (Heterozygous familial hypercholesterolemia) 3. Currently undergoing LDL (low-density lipoprotein) apheresis therapy QW (weekly) or Q2W (every 2 weeks) or at least 8 weeks prior to the screening visit Exclusion Criteria: 1. Homozygous FH (familial hypercholesterolemia) 2. Background medical LMT (lipid-modifying therapy) (if applicable) that has not been stable for at least 8 weeks prior to the screening visit 3. LDL apheresis schedule/ apheresis settings that have not been stable for at least 8 weeks prior to the screening visit 4. An LDL apheresis schedule other than QW to Q2W 5. Initiation of a new exercise program or exercise that has not remained stable within 8 weeks prior to the screening visit (week -2) 6. Initiation of a new diet or a diet that has not been stable within 8 weeks prior to the screening visit (week -2) 7. Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 8 weeks prior to the screening visit (week -2), or between the screening and randomization visit 8. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins 9. Known history of a positive test for human immunodeficiency virus 10. Use of any active investigational drugs within 1 month or 5 half-lives of screening, whichever is longer 11. Patients who have been treated with at least 1 dose of alirocumab or any other anti-PCSK9 monoclonal antibody in any other clinical studies 12. Pregnant or breastfeeding women

Locations (13)

Unnamed facility

Aurora, Colorado, United States

Unnamed facility

Hartford, Connecticut, United States

Unnamed facility

Kansas City, Kansas, United States

Unnamed facility

Scarborough, Maine, United States

Outcomes

Primary Outcomes

Change in Standardized Rate of Apheresis Treatments From Week 7 to Week 18

Rate of apheresis treatments were normalized by the number of planned apheresis treatments according to each participant's established schedule at screening, week -10 to week -2. The normalized rate of apheresis was defined for each participant as the number of actual apheresis treatments received from week 7 to week 18 divided by the number of planned apheresis treatments per randomization strata at baseline (6 for Q2W and 12 for QW).

Time frame: Week 7 to Week 18 (before start of open-label treatment)

Secondary Outcomes

Percent Change From Baseline in Calculated LDL-C (Pre-apheresis) at Week 6

Adjusted Least-squares (LS) means and standard errors at Week 6 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 2 to Week 18 regardless of status on or off-treatment were used in the model (ITT analysis).

Time frame: Baseline and at Week 6

Change in Standardized Rate of Apheresis Treatments From Week 15 to Week 18

Rate of apheresis treatments were normalized by the rate by the number of actual apheresis treatments according to received from week 15 to week 18 divided by the planned apheresis treatments per randomization strata at baseline (2 for Q2W and 4 for QW). Only legitimate apheresis treatment skipping per point-of-care LDL-C value is counted as "apheresis not occurred". Missing apheresis treatment information (any reason) from week 7 to week 18 is assigned an outcome of the apheresis treatment occurred at the visit (i.e. impute 1 apheresis treatment for that visit).

Time frame: Week 15 up to Week 18 (before the start of open-label treatment dose)

Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 6

Adjusted LS means and standard errors at Week 6 were obtained from MMRM to account for missing data. All available post-baseline data from Week 2 (pre-apheresis) to Week 18 (pre-apheresis) regardless of status on- or off-treatment were used in the model (ITT analysis).

Data from ClinicalTrials.gov

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Unnamed facility

Rochester, Minnesota, United States

Unnamed facility

Portland, Oregon, United States

Unnamed facility

Philadelphia, Pennsylvania, United States

Unnamed facility

Dresden, Saxony, Germany

Unnamed facility

Berlin, Germany

Unnamed facility

Göttingen, Germany

...and 3 more locations

Time frame: From Baseline to Week 6

Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) (Pre-apheresis) to Week 6

Time frame: From Baseline to Week 6

Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 6

Time frame: From Baseline to Week 6

Percent Change From Baseline in Apolipoprotein A (Apo A1) (Pre-apheresis) to Week 6

Time frame: From Baseline to Week 6

Percentage of Participants With At Least (>=) 30% Reduction in Calculated LDL-C (Pre-apheresis) at Week 6

Percentage of participants at Week 6 was obtained from a last observation carried forward (LOCF) model for handling of missing data. All available post-baseline data regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 6

Percentage of Participants With At Least (>=) 50% Reduction in Calculated LDL-C (Pre-apheresis) at Week 6

Percentage of participants at Week 6 was obtained from LOCF model for handling of missing data. All available post-baseline data regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 6

Percent Change From Baseline in Calculated LDL-C (Pre-Apheresis) to Week 18

Adjusted LS means and standard errors at Week 18 were obtained from MMRM to account for missing data. All available post-baseline data from Week 2 (pre-apheresis) to Week 18 (pre-apheresis) regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 18

Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 18

Time frame: From Baseline to Week 18

Percent Change From Baseline in Non-HDL-C (Pre-apheresis) to Week 18

Time frame: From Baseline to Week 18

Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 18

Time frame: From Baseline to Week 18

Percent Change From Baseline in Apo A1 (Pre-apheresis) to Week 18

Time frame: From Baseline to Week 18

Percentage of Participants With At Least (>=) 30% Reduction in Calculated LDL-C (Pre-apheresis) at Week 18

Percentage of participants at Week 18 was obtained from LOCF model for handling of missing data. All available post-baseline data regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 18

Percentage of Participants With At Least (>=) 50% Reduction in Calculated LDL-C (Pre-apheresis) at Week 18

Time frame: From Baseline to Week 18

Change From Baseline in W-BQ22 (Well-being Questionnaire) Index Score at Week 18

The W-BQ22 (well-being) questionnaire was a standardized and generic instrument used for measuring the impact of hypercholesterolemia and treatment on well-being of participants. The general well-being score was calculated as the sum of 22 questions in the W-BQ22 questionnaire (each question scored from 0 to 3 \[0 = not at all and 3 = all the time\]). Total score for 22 questions range from 0 to 66 \[0 = worst condition and 66 = best well-being condition).

Time frame: From Baseline to Week 18

Percent Change From Baseline in Lipoprotein (a) (Lp [a]) (Pre-apheresis) to Week 6

Adjusted means and standard errors at Week 6 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 2 (pre-apheresis) to Week 18 (pre-apheresis) regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 6

Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) (Pre-apheresis) to Week 6

Time frame: From Baseline to Week 6

Percent Change From Baseline in Triglyceride (TG) Levels (Pre-apheresis) to Week 6

Time frame: From Baseline to Week 6

Percent Change From Baseline in Lp (a) (Pre-apheresis) to Week 18

Adjusted means and standard errors at Week 18 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 2 (pre-apheresis) to Week 18 (pre-apheresis) regardless of status on- or off-treatment were used in the model (ITT analysis).

Time frame: From Baseline to Week 18

Percent Change From Baseline in HDL-C (Pre-apheresis) to Week 18

Time frame: From Baseline to Week 18

Percent Change From Baseline in TG Levels (Pre-apheresis) to Week 18

Time frame: From Baseline to Week 18