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    The EU Clinical Trials Register currently displays   44138   clinical trials with a EudraCT protocol, of which   7324   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:2008-003706-33
    Sponsor's Protocol Code Number:28821
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-03-12
    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 ConcernedFrance - ANSM
    A.2EudraCT number2008-003706-33
    A.3Full title of the trial
    A Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial of oral cladribine in subjects with a first clinical event at high risk of converting to MS
    A.3.2Name or abbreviated title of the trial where available
    ORAl CLadribine in Early MS (ORACLE MS) Trial
    A.4.1Sponsor's protocol code number28821
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck Serono International
    B.1.3.4CountrySwitzerland
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameCladribine
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCLADRIBINE
    D.3.9.1CAS number 4291638
    D.3.9.2Current sponsor code2-CdA
    D.3.9.3Other descriptive name2-chloro-2’-deoxy-ß-D-adenosine
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Yes
    D.2.1.1.1Trade name Rebif 44 micrograms solution for injection
    D.2.1.1.2Name of the Marketing Authorisation holderSerono Europe Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameInterferon beta-1a FBS-free/HSA-free
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNINTERFERON BETA-1A
    D.3.9.1CAS number 9008-11-1
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number44
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Subjects with a first clinical demyelinating event (Clinically Isolated Syndrome (CIS)) at high risk of converting to Multiple Sclerosis (MS)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level PT
    E.1.2Classification code 10028245
    E.1.2Term Multiple sclerosis
    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 this study, which will be determined during the Initial Treatment Period, is to evaluate the effect of 2 dosage regimens of oral cladribine vs. placebo on the time to conversion to Multiple Sclerosis (MS) (from randomization) according to the revised McDonald criteria in subjects with a first clinical demyelinating event at high risk of converting to MS.
    E.2.2Secondary objectives of the trial
    • Evaluate the effect of oral cladribine on the time to conversion to Clinical Definite Multiple Sclerosis (CDMS) according to the Poser criteria, defined by either a second attack or a sustained increase in EDSS score in subjects with a first clinical demyelinating event at high risk of converting to MS
    • Evaluate the effect of oral cladribine on selected MRI parameters and disease
    progression in subjects with a first clinical demyelinating event suggestive of MS
    • Evaluate the safety and tolerability of treatment with oral cladribine in subjects with a first clinical demyelinating event suggestive of MS
    • Evaluate the impact of CIS and oral cladribine on select patient-reported outcomes
    domains of the adapted Multiple Sclerosis Quality of Life (MSQOL-54) Scale and
    Treatment Satisfaction Scale.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Be male or female between 18 and 55 years old, inclusive (see Appendix C)
    2. Must weigh between 40-120 kg, inclusive
    3. Has experienced a single, first clinical event suggestive of MS within 75 days prior to the Screening visit, (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic, other than a paresthesia, vegetative or cerebral dysfunction
    4. Has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 mm, at least one of which is ovoid or periventricular or infratentorial on screening MRI
    5. Has EDSS 0 - 5.0 for at least one time point during the screening period before start of treatment with blinded study medication
    6. Have no medical history or evidence of latent tuberculosis infection (LTBI) or active
    tubercular disease (TB), as evidenced by TB skin test and/or chest X-ray
    7. The following hematological parameters must be normal (as defined below, inclusively) within 28 days of first dosing of blinded study medication at SD 1 (see also Section 6.2.1 for further Hematological Testing and Entry Guidelines):
    • Hemoglobin = 11.6 – 16.2 G/DL
    • Leukocytes (total white blood cells [WBC]) = 4.1 – 12.3 x10E3/UL
    • Absolute lymphocytes = 1.02 – 3.36 x10E3/UL
    • Absolute neutrophil count (ANC) = 2.03 – 8.36 x10E3/UL
    • Platelet count = 140 – 450 x10E3/UL
    8. If female, she must:
    • be neither pregnant nor breast-feeding, nor attempting to conceive and
    • use a highly effective method of contraception throughout the entire duration of the study and for 90 days following completion of the last dose of study medication. A highly effective method of contraception is defined as those which result in a low
    failure rate (i.e. less than1% per year) when used consistently and correctly such as
    implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or
    vasectomized partner, or
    • be post-menopausal or surgically sterilized
    [Note: for Danish sites only, subjects should use a hormonal contraceptive or intrauterine device for the duration of the trial]
    9. If male, he must be willing to use contraception to avoid contributing to pregnancies throughout the entire duration of the study and for 90 days following the last dose of study medication
    10. Be willing and able to comply with study procedures for the duration of the study
    11. Voluntarily provide written informed consent, including, for USA, subject authorization under Health Insurance Portability and Accountability Act (HIPAA) (see Appendix J), prior to any study-related procedure that is not part of normal medical care, and with the understanding that the subject may withdraw consent at any time without prejudice to their future medical care.
    NOTE: Confirmation that the subject is not pregnant must be established by a negative serum human chorionic gonadotropin (hCG) pregnancy test within 28 days of Study Day 1 and a negative urine pregnancy test on Study Day 1. A pregnancy test is not required if the subject is post-menopausal or surgically sterilized.
    E.4Principal exclusion criteria
    1. Subject has a diagnosis of multiple sclerosis (per McDonald criteria, 2005)
    2. Subject has any other disease that could better explain the subject’s signs and symptoms
    3. Subject has complete transverse myelitis or bilateral optic neuritis
    4. Subject uses or has used any other approved MS disease modifying drug (DMD)
    5. Subject has used any investigational drug (other than Rebif® New Formulation) or
    undergone an experimental procedure within 12 weeks prior to SD1 with the exclusion of MS drug
    6. Subject received oral or systemic corticosteroids or ACTH within 30 days prior to SD1
    7. Subject has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase
    8. Subject suffers from current autoimmune disease
    9. Subject suffers from psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk
    to the subject or could affect compliance with the study protocol
    10. Subject suffers from major medical illness such as cardiac (e.g. angina, congestive heart failure or arrhythmia), endocrinologic, hepatic, immunologic, metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine
    11. Subject has a history of seizures
    12. Subject has a known allergy to cladribine, IFN-beta, the excipient(s) of the study
    medications, or to gadolinium-DTPA
    13. Has any renal condition that would preclude the administration of gadolinium (e.g. acute or chronic severe renal insufficiency (GFR < 30 mL/min/1.73m2)
    14. Has a history of chronic or clinically significant hematological abnormalities
    15. History of active or chronic infectious disease or any disease that compromises immune function (e.g. HIV+, HTLV-1, Lyme disease, LTBI or TB, insulin-dependent diabetes).
    16. Subject has previously been screened in this study thus signed an informed consent and than withdrawn
    17. Subject has received any immunomodulatory or immunosuppressive therapy) at any time prior to Screening, including, but not limited to, the following products: any interferon, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (e.g. natalizumab, alemtuzumab/Campath, anti-CD4), intravenous immunoglobuline G (IVIG), cytokines or anti-cytokine therapy
    18. Subject has received experimental MS treatment
    19. Subject has a history of alcohol or drug abuse
    20. Subject has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
    21. Inability to administer subcutaneous injections either by self or by caregiver
    22. Has prior or current malignancy (with the exception of in situ basal or squamous cell skin cancer surgically removed without recurrence for at least five years)
    23. Have a positive stool heme-occult test at Screening
    E.5 End points
    E.5.1Primary end point(s)
    The single primary endpoint for the overall study, which will be determined during the
    Initial Treatment Period, is time to conversion to MS (from randomization), according to the revised McDonald criteria (2005).
    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 Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    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 No
    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.8.3 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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA130
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) No
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-03-12. Yes
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 450
    F.4.2.2In the whole clinical trial 642
    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 Decision2009-01-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-07-02
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-10-24
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