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    The EU Clinical Trials Register currently displays   44132   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:2007-006997-27
    Sponsor's Protocol Code Number:CRAD001M2301
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-01-20
    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 ConcernedGermany - BfArM
    A.2EudraCT number2007-006997-27
    A.3Full title of the trial
    A randomized, double-blind, placebo-controlled study of RAD001 in the treatment of patients with subependymal giant cell astrocytomas (SEGA) associated with Tuberous Sclerosis Complex (TSC)
    A.3.2Name or abbreviated title of the trial where available
    N/A
    A.4.1Sponsor's protocol code numberCRAD001M2301
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberN/A
    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 SponsorNovartis Pharma Services AG
    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 nameRAD001 1mg
    D.3.2Product code RAD001
    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 INNeverolimus
    D.3.9.1CAS number 159351696
    D.3.9.2Current sponsor codeRAD001
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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.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
    This study will evaluate the antitumor activity of RAD001 versus placebo in patients
    with subependymal giant cell astrocytomas (SEGA) associated with Tuberous
    Sclerosis Complex (TSC).
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Information not present in EudraCT
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the SEGA response rate in patients with TSC-associated SEGA on
    RAD001 versus placebo.
    E.2.2Secondary objectives of the trial
    To compare RAD001 versus placebo with respect to:
    1. Change from baseline in frequency of epileptiform events.
    2. Time to SEGA progression.
    3. Skin lesion response rate.
    4. Change from baseline in plasma angiogenic molecules, e.g. VEGF, basic FGF,
    PLGF, soluble VEGF receptor1, and soluble VEGF receptor2.
    5. Renal function assessed using calculated creatinine clearance.
    6. Safety as assessed by the NCI Common Toxicity Criteria, version 3.0.

    In RAD001 treatment arm to :
    7. Characterize the pharmacokinetics of RAD001 in this patient population,
    specifically in terms of exposure.
    8. Describe the duration of SEGA response, the time to SEGA response and the
    duration of skin lesion response.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female of any age.
    2. Clinically definite diagnosis of tuberous sclerosis according to the modified
    Gomez criteria (Roach et al, 1998; Hyman and Whittemore, 2000, Table 5-1).
    Clinically definite diagnosis is defined as either of the following:
    a. Two Major Features from Table 5-1.
    b. One Major Feature plus two Minor Features from Table 5-1.
    3. Presence of at least one SEGA lesion ≥ 1.0 cm in its longest diameter using
    MRI.
    Note: SEGA lesions are only diagnosed in patients with TSC. They arise in the
    subependymal layer of the lateral ventricle and are always located near the
    foramen of Monro and enhance homogeneously with contrast on MRI with no
    evidence of surrounding edema.
    4. A recent MRI of the brain completed within 3 weeks (21 days) prior to the
    patient’s randomization must be compared with an MRI of the brain performed at
    an earlier stage of patient care (pre-baseline) and should demonstrate at least one of the following:
    a. Serial growth, defined as at least a 25% increase in SEGA volume, or
    b. Presence of a new SEGA lesion ≥ 1 cm in its longest diameter, or
    c. New or worsening hydrocephalus defined by assessment of ventricular
    configuration changes, ventricular cap signs (periventricular edema) and
    qualitative assessment of CSF flow dynamics.
    Notes:
    If a previous MRI is not available, a comparative review of two previous CT scans is
    also acceptable to establish any of the above mentioned three conditions. In this
    case, baseline/screening MRI should still be performed.
    If only one prior CT scan was available, a second CT scan should be obtained to
    allow like to like comparison of cranial images. Again, the baseline MRI should still
    be performed. CT scans should be digitized and sent to the central reviewer for
    confirmation of eligibility.
    If the pre-baseline MRI or CT was only available on film (non-digital format) or
    software for volumetric assessment was not available at the local site, the local
    radiologist should make a qualitative assessment of the above-mentioned three
    criteria. The non-digital MRI or CT must also be sent to Central Radiology for
    review.
    5. If female and of child bearing potential, documentation of negative pregnancy
    test prior to enrollment. Sexually active pre-menopausal female patients (and
    female partners of male patients) must use adequate contraceptive measures,
    excluding estrogen containing contraceptives, while on study.
    6. Written informed consent. Parents or legal guardians must sign the informed
    consent for patients under 18 years old and for patients with developmental
    delays. In addition, all minors aged 7 through 14 must sign an assent form, while
    minors aged 15 up to 17 must sign an assent line on the Informed Consent Form
    that will be signed by the parents or the legal guardians.
    E.4Principal exclusion criteria
    1. Patients for whom SEGA related surgery is likely to be required, in the opinion of
    the investigator.
    2. Prior brain surgery.
    3. History of myocardial infarction, angina or stroke related to atherosclerosis
    4. Impaired lung function, defined as any of the following:
    a. FEV1 ≤ 70% of predicted, or
    b. DLCO ≤ 70% of predicted, or
    c. ≤ 88% O2 saturation at rest in room air, or
    d. for patients unable to perform pulmonary function testing:
    i. clinical evidence of significantly impaired lung function, or
    ii. radiological evidence of significant lung disease other than LAM
    Note: Patients unable to perform a pulmonary function test (e.g. younger children,
    patients with developmental delay) will have a baseline chest CT scan performed
    5. Significant hematological or hepatic abnormality (i.e. transaminase levels > 2.5 x
    ULN or serum bilirubin > 1.5 x ULN, hemoglobin < 9 g/dL, platelets < 80,000/
    mm3, absolute neutrophil count < 1,000/mm3).
    6. Pregnancy or breast feeding.
    7. Intercurrent infection at date of randomization.
    8. Prior history of organ transplant.
    9. Recent surgery (involving entry into a body cavity or requiring sutures) within the
    2 months prior to randomization.
    10. Prior therapy with mTOR inhibitors (e.g.sirolimus, temsirolimus, everolimus).
    11. Use of an investigational drug within the 30 days prior to randomization.
    12. Uncontrolled hyperlipidemia: Fasting serum cholesterol > 300 mg/dL OR > 7.75
    mmol/L AND Fasting triglycerides > 2.5 x ULN.
    13. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN.
    14. Patients with bleeding diathesis or on oral anti-vitamin K medication (except low
    dose warfarin).
    15. Patients with known history of HIV seropositivity.
    16. Inability to attend scheduled clinic visits.
    17. For the purpose of MRI assessments:
    a. Ferromagnetic metal implants (e.g., braces, some types of aneurysm clips,
    shrapnel) unless approved as safe for use in MR scanner
    b. Patients suffering from uncontrollable claustrophobia or physically unable to fit
    into the machine (e.g., obesity, etc).
    18. Serum creatinine > 1.5 x ULN.
    19. History of malignancy in the past two years, other than squamous or basal cell
    skin cancer.
    20. Use of estrogen containing medications.
    E.5 End points
    E.5.1Primary end point(s)
    SEGA response rate is determined from the Independent
    Central Radiological Review of MRIs. SEGA response rate is defined as the
    proportion of patients with a reduction in SEGA volume of at least 50% relative to
    baseline, where SEGA volume is the sum of the volumes of all target SEGA lesions
    identified at baseline, and confirmed with a second scan at least 4 weeks later.
    In addition, response requires that:
    • the non-target SEGA lesions have not unequivocally worsened
    • no new SEGA lesions (of ≥1cm) are identified
    • there is no new or worsening hydrocephalus, defined by central radiological
    assessment of ventricular configuration changes, ventricular cap signs
    (periventricular edema) and quantitative assessment of CSF flow dynamics.
    SEGA response rate will be determined in the Full Analysis Set (FAS), defined as all
    randomized patients analyzed according to the treatment they were assigned to at
    randomization.
    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 Information not present in EudraCT
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence Information not present in EudraCT
    E.6.9Dose response Information not present in EudraCT
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Information not present in EudraCT
    E.6.12Pharmacoeconomic Information not present in EudraCT
    E.6.13Others Information not present in EudraCT
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    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 years3
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months9
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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) Yes
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.5Children (2-11years) Yes
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 37
    F.4.2.2In the whole clinical trial 99
    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 Decision2010-02-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-03-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-10-02
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