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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   38002   clinical trials with a EudraCT protocol, of which   6235   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
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    EudraCT Number:2014-001917-20
    Sponsor's Protocol Code Number:R727-CL-1216.03
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-11-25
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2014-001917-20
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to explore the safety and efficacy of alirocumab in patients that require Apheresis to control their blood lipid levels
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberR727-CL-1216.03
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorRegeneron Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportRegeneron Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRegeneron Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointGaren Manvelian
    B.5.3 Address:
    B.5.3.1Street Address777 Old Saw Mill River Road
    B.5.3.2Town/ cityTarrytown
    B.5.3.3Post codeNY 10591
    B.5.3.4CountryUnited States
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAlirocumab
    D.3.2Product code SAR236553/REGN727
    D.3.4Pharmaceutical form Solution for injection in pre-filled pen
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAlirocumab
    D.3.9.1CAS number 1245916-14-6
    D.3.9.2Current sponsor codeAlirocumab/SAR236553/REGN727
    D.3.9.3Other descriptive nameALIROCUMAB
    D.3.9.4EV Substance CodeSUB74847
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection in pre-filled pen
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Heterozygous Familial Hypercholesterolemia
    E.1.1.1Medical condition in easily understood language
    Hereditary abnormal (high) cholesterol level that cannot be treated with standard medicines therapy
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10057079
    E.1.2Term Heterozygous familial hypercholesterolemia
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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 patients with heterozygous familial hypercholesterolemia (HeFH) undergoing weekly or bi-weekly LDL apheresis therapy.
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    • To evaluate the effect of alirocumab 150 mg Q2W on LDL-C levels in patients with HeFH undergoing LDL apheresis therapy
    • To evaluate the effect of alirocumab 150 mg Q2W on the following lipid parameters: ApoB, non-HDL-C, total cholesterol, Lp(a), HDL-C, TGs, and ApoA-1 in patients with HeFH undergoing LDL apheresis therapy during the study
    • To evaluate the safety and tolerability of alirocumab 150 mg Q2W in patients with HeFH undergoing LDL apheresis therapy
    • To assess the PK of alirocumab 150 mg Q2W in patients with HeFH undergoing LDL apheresis therapy (QW versus Q2W)
    • To evaluate the development of anti-alirocumab antibodies
    • To evaluate PCSK9 levels in response to alirocumab therapy as well as pre and post-apheresis
    • To evaluate QOL in patients
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    An optional genomic sub-study will be conducted to identify genetic associations with clinical or biomarker response to PCSK9 inhibition, hyperlipidemia, or CVD. Samples may also be used to identify markers associated with toxicity.
    E.3Principal inclusion criteria
    A patient must meet the following criteria to be eligible for inclusion in the study:
    1. Men and women ≥18 years of age at the time of the screening visit
    2. Diagnosis of HeFH
    3. Currently undergoing LDL apheresis therapy QW for at least 4 weeks, or Q2W for at least 8 weeks prior to the screening visit (week -2) and have initiated apheresis treatment for at least 5 months prior to that
    Note: A stable apheresis schedule is considered as 4 apheresis procedures performed during a 4-week period, approximately 1 week apart, or 4 apheresis procedures performed during an
    8-week period, approximately 2 weeks apart.
    E.4Principal exclusion criteria
    A patient who meets any of the following criteria will be excluded from the study:
    1. Homozygous FH
    2. Background medical LMT (if applicable) that has not been stable for at least 8 weeks prior to the screening visit (week -2)
    3. LDL apheresis schedule/apheresis settings that have not been stable for at least 4 weeks prior to the screening visit (week -2) for patients undergoing apheresis weekly and at least 8 weeks prior to the screening visit (week -2) for patients undergoing apheresis bi weekly
    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. Signs and symptoms of hypothyroidism (thyroid replacement therapy is permitted)
    10. History of bariatric surgery within 12 months prior to the screening visit (week -2)
    11. Unstable weight (variation >5 kg) within 2 months prior to the screening visit (week -2)
    12. Newly diagnosed (within 3 months prior to randomization visit [day 1]) diabetes mellitus or poorly controlled (hemoglobin A1c [HbA1c] >9%) diabetes
    13. Use of systemic corticosteroids, unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to randomization; topical, intra-articular, nasal, inhaled and ophthalmic steroid therapies are not considered
    as ‘systemic’ and are allowed
    14. Use of estrogen or testosterone therapy, unless the regimen has been stable in the past 6 weeks prior to the screening visit (week -2) and no plans to change the regimen during the study
    15. Systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg at the
    screening visit (week -2) or time of randomization (day 1)
    Note: Blood pressure assessment for study eligibility may be obtained at a visit occurring
    between these 2 visits in the event that the patient had not taken, or plans not to take,
    prescribed hypertensive medications at the screening or randomization visit due to
    apheresis schedule.
    16. History of a myocardial infarction (MI), unstable angina leading to hospitalization,
    coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI),
    uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic
    attack or carotid revascularization within 3 months prior to the screening visit (week -2),
    or endovascular procedure or surgical intervention for peripheral vascular disease within
    1 month prior to the screening visit (week -2)
    17. History of New York Heart Association Class III or IV heart failure within 12 months prior to the screening visit
    18. Known history of a hemorrhagic stroke
    19. History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
    20. Known history of a positive test for human immunodeficiency virus
    21. Use of any active investigational drugs within 1 month or 5 half-lives of screening, whichever is longer
    22. Patients who have been treated with at least 1 dose of alirocumab or any other anti-PCSK9 monoclonal antibody in any other clinical studies
    23. Conditions/situations such as:
    - Any clinically significant abnormality identified at the time of screening that, in the judgment of the investigator or any sub-investigator, would preclude safe completion of the study or constrain endpoints assessment; eg, major systemic diseases, patients with short life expectancy
    - Considered by the investigator or any sub-investigator as inappropriate for this study for any reason, eg:
    - Deemed unable to meet specific protocol requirements, such as scheduled visits
    - Deemed unable to tolerate injections, as per the patient or the investigator
    - Investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc
    - Presence of any other conditions (eg, geographic or social), either actual or anticipated, that the investigator feels would restrict or limit the patient’s participation for the duration of the study
    24. Certain laboratory findings during screening period
    25. Known hypersensitivity to monoclonal antibody therapeutics or to any component of the drug product
    26. Pregnant or breastfeeding women
    27. Women of childbearing potential not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is the rate of apheresis treatments during the
    12-week period from week 7 to week 18, normalized by the number of planned apheresis treatments according to each patient’s established schedule at screening, week -10 to week -2.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Throughout the duration of the study
    E.5.2Secondary end point(s)
    The key secondary endpoints are:
    • Percent change from baseline in LDL-C (pre-apheresis) to week 6, regardless of adherence to treatment
    • The standardized rate of apheresis treatments during the 4-week period from week 15 to week 18, defined similarly as for the primary efficacy endpoint
    • Percent change from baseline in (pre-apheresis): ApoB, non-HDL-C, total cholesterol and ApoA-1to week 6, regardless of adherence to treatment
    • Proportion of patients with ≥30% and ≥50% reduction in LDL-C (pre-apheresis) at week 6, regardless of adherence to treatment
    • Percent change from baseline in (pre-apheresis): LDL-C, ApoB, non-HDL-C, total cholesterol, in ApoA-1 to week 18, regardless of adherence to treatment
    • Proportion of patients with ≥30% and ≥50% reduction in LDL-C (pre-apheresis) at week 18, regardless of adherence to treatment
    • Change of W-BQ22 index score from baseline to week 18, regardless of adherence to treatment
    • Percent change from baseline in (pre-apheresis): Lp(a), HDL-C and TG levels to week 6, regardless of adherence to treatment
    • Percent change from baseline in (pre-apheresis): Lp(a), HDL-C and TG levels to week 18, regardless of adherence to treatment
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the duration of the study
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E. trial design description
    Added an open-label treatment period
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last visit of last subject - LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months17
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 33
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state42
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 42
    F.4.2.2In the whole clinical trial 63
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After participation in the trial, patients will receive their standard
    medical care.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-02-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-13
    P. End of Trial
    P.End of Trial StatusCompleted
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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