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    The EU Clinical Trials Register currently displays   43850   clinical trials with a EudraCT protocol, of which   7282   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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    Summary
    EudraCT Number:2015-000620-28
    Sponsor's Protocol Code Number:LPS14245
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-08-27
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSweden - MPA
    A.2EudraCT number2015-000620-28
    A.3Full title of the trial
    A Multi-Country, Multicenter, Single-Arm, Open-Label Study to Document the Safety, Tolerability and Effect of Alirocumab on atherogenic lipoproteins in High Cardio-Vascular Risk Patients With Severe Hypercholesterolemia Not Adequately Controlled With Conventional Lipid-Modifying Therapies
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety, Tolerability, and Effect of Alirocumab in High Cardiovascular Risk Patients with Severe Hypercholesterolemia Not Adequately Controlled with Conventional Lipid-modifying Therapies
    A.3.2Name or abbreviated title of the trial where available
    APPRISE
    A.4.1Sponsor's protocol code numberLPS14245
    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 Sponsorsanofi-aventis groupe
    B.1.3.4CountryFrance
    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 supportSanofi-aventis groupe
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSanofi AB
    B.5.2Functional name of contact pointCountry Team Manager Sweden
    B.5.3 Address:
    B.5.3.1Street AddressLindhagensgatan 120
    B.5.3.2Town/ cityStockholm
    B.5.3.3Post code10425
    B.5.3.4CountrySweden
    B.5.4Telephone number+ 46 8 634 5000
    B.5.5Fax number+ 46 8 634 5001
    B.5.6E-mailclinicaltrials.sweden@sanofi.com
    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 codeSAR236553 (REGN727)
    D.3.9.4EV Substance CodeSUB74847
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) Yes
    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.IMP: 2
    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 codeSAR236553 (REGN727)
    D.3.9.4EV Substance CodeSUB74847
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Hypercholesterolemia
    E.1.1.1Medical condition in easily understood language
    Hypercholesterolemia
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10020603
    E.1.2Term Hypercholesterolaemia
    E.1.2System Organ Class 10027433 - Metabolism and nutrition disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To provide patients with severe hypercholesterolemia at risk for subsequent cardiovascular (CV) events and not adequately controlled with currently available lipid-modifying therapy (LMT) access to alirocumab ahead of commercial availability and to document the overall safety and tolerability of alirocumab in this patient population.
    E.2.2Secondary objectives of the trial
    To document the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels as well as non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels after 12 weeks of treatment.
    To document patient’s acceptability of self-injection (Self Injection Assessment Questionnaire, SIAQ).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Either A, B, C, D, or E below and not adequately controlled with a maximally tolerated dose of statin with or without other LMTs, all at stable doses for at least 4 weeks prior to the screening visit (Week 3):
    A. Patients suffering from heterozygous familial hypercholesterolemia (heFH) with LDL-C concentrations ≥160 mg/dL (4.14 mmol/L) despite treatment.
    B. Patients suffering from heFH with LDL-C concentrations ≥130 mg/dL (3.36 mmol/L) despite treatment and two or more CV risk factors among this list:
    - LDL-C >250 mg/dL (6.46 mmol/L) at the time of the FH diagnosis (before treatment).
    - Family history of premature-onset coronary heart disease (CHD; first-degree male relative with onset before age 55 years; first-degree female relative with onset before age 65 years).
    - Metabolic syndrome.
    - HDL-C <40 mg/dL (1.03 mmol/L).
    - Hypertension (blood pressure >140/90 mmHg or drug treatment).
    - Lipoprotein a (Lp[a]) ≥50 mg/dL (1.78 µmol/L).
    - Tendon xanthoma.
    C. Patients suffering from heFH with LDL-C concentrations ≥130 mg/dL (3.36 mmol/L) despite treatment and one of the following characteristics:
    - Established CHD or other cardiovascular disease (CVD; history of acute myocardial infarction, ischemic stroke, peripheral arterial disease, coronary or peripheral arterial revascularization, stable or unstable angina, transient ischemic attack, carotid artery stenosis ≥50%, or aortic abdominal aneurysm).
    - Drug-treated type 2 diabetes mellitus or type 1 with target organ damage.
    - Family history of first- or second-degree relative with very premature onset CHD (first- or second degree male relative with onset before age 45; first- or second-degree female relative with onset before age 55).
    D. Non-FH patients suffering from established CHD or other CVD (history of acute myocardial infarction, ischemic stroke, peripheral arterial disease, coronary or peripheral arterial revascularization, stable or unstable angina, transient ischemic attack, carotid artery stenosis ≥50%, or aortic abdominal aneurysm) and with LDL-C concentrations ≥130 mg/dL (3.36 mmol/L).
    E. Patients suffering from progressive CVD (coronary artery disease, or peripheral arterial occlusive disease or cerebrovascular disease as documented clinically or by imaging techniques, with a subsequent CV event [acute MI, ischemic stroke, ischemia-driven revascularization, unstable angina, transient ischemic attack] occurring despite stable doses of maximally tolerated LLT) with LDL-C concentrations ≥100 mg/dL (2.59 mmol/L).
    E.4Principal exclusion criteria
    Not on a stable dose of LMT (including statin) for at least 4 weeks prior to the screening visit (Week 3) and from screening to enrollment.
    Use of a fibrate other than fenofibrate within 4 weeks of the screening visit (Week 3) or between screening and enrollment.
    Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except for patients on simvastatin 80 mg for more than one year, who are eligible).
    Use of statin other than simvastatin, atorvastatin, or rosuvastatin prior to the screening visit (Week 3) or between screening and enrollment, except when there is a documented reason for intolerance to the abovementioned potent statins (in which case the use of a different statin is allowed).
    Fasting serum TG >400 mg/dL (>4.52 mmol/L) at the screening visit (Week 3).
    Uncontrolled hypertension (>180 mmHg systolic and/or >110 mmHg diastolic at randomization visit).
    New York Heart Association Class III or IV congestive heart failure persisting despite treatment.
    History of hemorrhagic stroke.
    Liver transaminases >3 times the upper limit of normal.
    Laboratory evidence of current hepatitis B or C infection.
    Creatine kinase >3 times the upper limit of normal.
    Estimated glomerular filtration rate <30 mL/min/1.73 m^2.
    Pregnant or breastfeeding woman or with childbearing potential without appropriate contraception.
    Patients eligible for enrollment into an ongoing clinical study of alirocumab conducted at the same investigational site.
    Hypersensitivity to alirocumab or any of the excipients.
    E.5 End points
    E.5.1Primary end point(s)
    a) Proportion of patients with adverse events
    b) Change from baseline in laboratory data (hematology and biochemistry)
    c) Change from baseline in vital signs
    E.5.1.1Timepoint(s) of evaluation of this end point
    a), b), c) : up to 30 months
    E.5.2Secondary end point(s)
    a) Assessment of patient’s acceptability of self-injection using Self Injection Assessment Questionnaire (SIAQ)
    b) Percent change from baseline in calculated LDL-C levels
    c) Percent change from baseline in total-C levels
    d) Percent change from baseline in HDL-C levels
    e) Percent change from baseline in TG levels
    E.5.2.1Timepoint(s) of evaluation of this end point
    a) : Up to 30 months
    b), c), d), e): Baseline to week 12
    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 No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    provide early access to high-risk patients ahead of alirocumab commercial availability
    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.7.1.3.1Other 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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.2.4Number of treatment arms in the trial1
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA124
    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
    Canada
    Switzerland
    E.8.7Trial has a data monitoring committee No
    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
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days15
    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: 650
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 450
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 955
    F.4.2.2In the whole clinical trial 1100
    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)
    none
    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 Decision2015-09-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-23
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-04-12
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