- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02326220
Study of Alirocumab (REGN727/SAR236553) in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) Undergoing Low-density Lipoprotein (LDL) Apheresis Therapy (ODYSSEY ESCAPE)
April 21, 2020 updated by: Regeneron Pharmaceuticals
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
62
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Berlin, Germany
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Göttingen, Germany
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Muenchen (2 locations), Germany
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Passau, Germany
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Rostock, Germany
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Sachsen
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Dresden, Sachsen, Germany
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Colorado
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Aurora, Colorado, United States
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Connecticut
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Hartford, Connecticut, United States
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Kansas
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Kansas City, Kansas, United States
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Maine
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Scarborough, Maine, United States
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Minnesota
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Rochester, Minnesota, United States
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Oregon
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Portland, Oregon, United States
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Pennsylvania
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Philadelphia, Pennsylvania, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Men and women ≥18 years of age at the time of the screening visit
- Diagnosis of HeFH (Heterozygous familial hypercholesterolemia)
- 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:
- Homozygous FH (familial hypercholesterolemia)
- Background medical LMT (lipid-modifying therapy) (if applicable) that has not been stable for at least 8 weeks prior to the screening visit
- LDL apheresis schedule/ apheresis settings that have not been stable for at least 8 weeks prior to the screening visit
- An LDL apheresis schedule other than QW to Q2W
- Initiation of a new exercise program or exercise that has not remained stable within 8 weeks prior to the screening visit (week -2)
- Initiation of a new diet or a diet that has not been stable within 8 weeks prior to the screening visit (week -2)
- 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
- Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
- Known history of a positive test for human immunodeficiency virus
- Use of any active investigational drugs within 1 month or 5 half-lives of screening, whichever is longer
- Patients who have been treated with at least 1 dose of alirocumab or any other anti-PCSK9 monoclonal antibody in any other clinical studies
- Pregnant or breastfeeding women
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Placebo Q2W (Double Blind Period)
Placebo (for alirocumab) subcutaneous (SC) injection Q2W up to Week 16.
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Experimental: Alirocumab 150 mg Q2W (Double Blind Period)
Alirocumab 150 mg SC injection Q2W up to Week 16.
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Other Names:
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Experimental: Alirocumab 150 Q2W (Open Label Treatment Period)
Alirocumab 150 mg SC injection Q2W starting from Week 18 up to Week 76.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Standardized Rate of Apheresis Treatments From Week 7 to Week 18
Time Frame: Week 7 to Week 18 (before start of open-label treatment)
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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).
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Week 7 to Week 18 (before start of open-label treatment)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline in Calculated LDL-C (Pre-apheresis) at Week 6
Time Frame: Baseline and at Week 6
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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).
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Baseline and at Week 6
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Change in Standardized Rate of Apheresis Treatments From Week 15 to Week 18
Time Frame: Week 15 up to Week 18 (before the start of open-label treatment dose)
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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).
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Week 15 up to Week 18 (before the start of open-label treatment dose)
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Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 6
Time Frame: From Baseline to Week 6
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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).
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From Baseline to Week 6
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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
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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).
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From Baseline to Week 6
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Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 6
Time Frame: From Baseline to Week 6
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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).
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From Baseline to Week 6
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Percent Change From Baseline in Apolipoprotein A (Apo A1) (Pre-apheresis) to Week 6
Time Frame: From Baseline to Week 6
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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).
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From Baseline to Week 6
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Percentage of Participants With At Least (>=) 30% Reduction in Calculated LDL-C (Pre-apheresis) at Week 6
Time Frame: From Baseline to Week 6
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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).
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From Baseline to Week 6
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Percentage of Participants With At Least (>=) 50% Reduction in Calculated LDL-C (Pre-apheresis) at Week 6
Time Frame: From Baseline to Week 6
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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).
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From Baseline to Week 6
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Percent Change From Baseline in Calculated LDL-C (Pre-Apheresis) to Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percent Change From Baseline in Non-HDL-C (Pre-apheresis) to Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percent Change From Baseline in Apo A1 (Pre-apheresis) to Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percentage of Participants With At Least (>=) 30% Reduction in Calculated LDL-C (Pre-apheresis) at Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percentage of Participants With At Least (>=) 50% Reduction in Calculated LDL-C (Pre-apheresis) at Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Change From Baseline in W-BQ22 (Well-being Questionnaire) Index Score at Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percent Change From Baseline in Lipoprotein (a) (Lp [a]) (Pre-apheresis) to Week 6
Time Frame: From Baseline to Week 6
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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).
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From Baseline to Week 6
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Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) (Pre-apheresis) to Week 6
Time Frame: From Baseline to Week 6
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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).
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From Baseline to Week 6
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Percent Change From Baseline in Triglyceride (TG) Levels (Pre-apheresis) to Week 6
Time Frame: From Baseline to Week 6
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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).
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From Baseline to Week 6
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Percent Change From Baseline in Lp (a) (Pre-apheresis) to Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percent Change From Baseline in HDL-C (Pre-apheresis) to Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Percent Change From Baseline in TG Levels (Pre-apheresis) to Week 18
Time Frame: From Baseline to Week 18
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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).
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From Baseline to Week 18
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 31, 2015
Primary Completion (Actual)
January 31, 2016
Study Completion (Actual)
April 30, 2016
Study Registration Dates
First Submitted
December 22, 2014
First Submitted That Met QC Criteria
December 22, 2014
First Posted (Estimate)
December 29, 2014
Study Record Updates
Last Update Posted (Actual)
May 1, 2020
Last Update Submitted That Met QC Criteria
April 21, 2020
Last Verified
April 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- R727-CL-1216
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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