Clinical trial NCT02326220: Study of Alirocumab (REGN727/SAR236553) in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) Undergoing Low-density Lipoprotein (LDL) Apheresis Therapy
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia Undergoing Lipid Apheresis Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heterozygous Familial Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2014-12-29
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Standardized Rate of Apheresis Treatments From Week 7 to Week 18
timeFrame: Week 7 to Week 18 (before start of open-label treatment)
Secondary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C (Pre-apheresis) at Week 6
timeFrame: Baseline and at Week 6
measure: Change in Standardized Rate of Apheresis Treatments From Week 15 to Week 18
timeFrame: Week 15 up to Week 18 (before the start of open-label treatment dose)
measure: Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 6
timeFrame: From Baseline to Week 6
measure: Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) (Pre-apheresis) to Week 6
timeFrame: From Baseline to Week 6
measure: Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 6
timeFrame: From Baseline to Week 6
measure: Percent Change From Baseline in Apolipoprotein A (Apo A1) (Pre-apheresis) to Week 6
timeFrame: From Baseline to Week 6
measure: Percentage of Participants With At Least (>=) 30% Reduction in Calculated LDL-C (Pre-apheresis) at Week 6
timeFrame: From Baseline to Week 6
measure: Percentage of Participants With At Least (>=) 50% Reduction in Calculated LDL-C (Pre-apheresis) at Week 6
timeFrame: From Baseline to Week 6
measure: Percent Change From Baseline in Calculated LDL-C (Pre-Apheresis) to Week 18
timeFrame: From Baseline to Week 18
measure: Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 18
timeFrame: From Baseline to Week 18
measure: Percent Change From Baseline in Non-HDL-C (Pre-apheresis) to Week 18
timeFrame: From Baseline to Week 18
measure: Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 18
timeFrame: From Baseline to Week 18
measure: Percent Change From Baseline in Apo A1 (Pre-apheresis) to Week 18
timeFrame: From Baseline to Week 18
measure: Percentage of Participants With At Least (>=) 30% Reduction in Calculated LDL-C (Pre-apheresis) at Week 18
timeFrame: From Baseline to Week 18
measure: Percentage of Participants With At Least (>=) 50% Reduction in Calculated LDL-C (Pre-apheresis) at Week 18
timeFrame: From Baseline to Week 18
measure: Change From Baseline in W-BQ22 (Well-being Questionnaire) Index Score at Week 18
timeFrame: From Baseline to Week 18
measure: Percent Change From Baseline in Lipoprotein (a) (Lp [a]) (Pre-apheresis) to Week 6
timeFrame: From Baseline to Week 6
measure: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) (Pre-apheresis) to Week 6
timeFrame: From Baseline to Week 6
measure: Percent Change From Baseline in Triglyceride (TG) Levels (Pre-apheresis) to Week 6
timeFrame: From Baseline to Week 6
measure: Percent Change From Baseline in Lp (a) (Pre-apheresis) to Week 18
timeFrame: From Baseline to Week 18
measure: Percent Change From Baseline in HDL-C (Pre-apheresis) to Week 18
timeFrame: From Baseline to Week 18
measure: Percent Change From Baseline in TG Levels (Pre-apheresis) to Week 18
timeFrame: From Baseline to Week 18
Other outcomes:
Locations:
city: Aurora
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: Kansas City
country: United States
state: Kansas
city: Scarborough
country: United States
state: Maine
city: Rochester
country: United States
state: Minnesota
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Dresden
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Göttingen
country: Germany
city: Muenchen (2 locations)
country: Germany
city: Passau
country: Germany
city: Rostock
country: Germany
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Moriarty PM, Parhofer KG, Babirak SP, Cornier MA, Duell PB, Hohenstein B, Leebmann J, Ramlow W, Schettler V, Simha V, Steinhagen-Thiessen E, Thompson PD, Vogt A, von Stritzky B, Du Y, Manvelian G. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J. 2016 Dec 21;37(48):3588-3595. doi: 10.1093/eurheartj/ehw388. Epub 2016 Aug 29.
citation: Moriarty PM, Parhofer KG, Babirak SP, deGoma E, Duell PB, Hohenstein B, Ramlow W, Simha V, Steinhagen-Thiessen E, Thompson PD, Vogt A, von Stritzky B, Du Y, Manvelian G. Alirocumab in patients with heterozygous familial hypercholesterolemia undergoing lipoprotein apheresis: Rationale and design of the ODYSSEY ESCAPE trial. J Clin Lipidol. 2016 May-Jun;10(3):627-34. doi: 10.1016/j.jacl.2016.02.003. Epub 2016 Feb 18.