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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
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    The EU Clinical Trials Register currently displays   43800   clinical trials with a EudraCT protocol, of which   7272   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
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    EudraCT Number:2007-006997-27
    Sponsor's Protocol Code Number:CRAD001M2301
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-07-06
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    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
    A.4.1Sponsor's protocol code numberCRAD001M2301
    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.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.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharmaceuticals UK Ltd
    B.5.2Functional name of contact pointMedical Information Services
    B.5.3 Address:
    B.5.3.1Street AddressFrimley Business Park
    B.5.3.2Town/ cityFrimley, Surrey
    B.5.3.3Post codeGU16 7SR
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number441276698370
    B.5.5Fax number441276698449
    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 round tablets
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product Information not present in EudraCT
    D. ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D. 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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare SEGA response rate on RAD001 versus placebo in patients with TSC-associated SEGA.
    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
    Note: SEGA lesions are only diagnosed in patients with TSC. They arise in the
    subependymal layer of the lateral ventricle and are usually 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 4 weeks (28 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: Patients who have had previous SEGA surgery are eligible provided criterion 4 has been satisfied by comparing the baseline scan to any pre-baseline scan that has been conducted following the most recent SEGA surgery.
    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, a 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 must be digitized and sent to the central reviewer for
    confirmation of eligibility.
    If the pre-baseline MRI or CT scan 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 scan must also be sent to Central Radiology for
    5. If female and of child bearing potential, documentation of negative pregnancy test prior to enrollment. Sexually active pre-menopausal female patients must use adequate contraceptive measures, while on study and for up to 8 weeks after ending treatment.
    6. Written informed consent according to local guidelines.
    E.4Principal exclusion criteria
    1. Patients for whom SEGA related surgery is likely to be required, in the opinion of
    the investigator.
    2. History of myocardial infarction, angina or stroke related to atherosclerosis
    3. Known impaired lung function (e.g. FEV1 or DLCO ≤ 70% of predicted)
    4. 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).
    5. Pregnancy or breast feeding.
    6. Intercurrent infection at date of randomization.
    7. Prior history of organ transplant.
    8. Recent surgery (involving entry into a body cavity or requiring sutures) within the
    2 months prior to randomization.
    9. Prior therapy with mTOR inhibitors (e.g.sirolimus, temsirolimus, everolimus).
    10. Use of an investigational drug within the 30 days prior to randomization.
    11. Uncontrolled hyperlipidemia: Fasting serum cholesterol > 300 mg/dL OR > 7.75
    mmol/L AND Fasting triglycerides > 2.5 x ULN.
    12. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN.
    13. Patients with bleeding diathesis or on oral anti-vitamin K medication (except low
    dose warfarin).
    14. Patients with known history of HIV seropositivity.
    15. Inability to attend scheduled clinic visits.
    16. 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).
    Note: patints with vagal nerve stimulators are permitted to have CT assessments of angiomyolipomas unless local or national regulations do not permit this.
    17. Serum creatinine > 1.5 x ULN.
    18. History of malignancy in the past two years, other than squamous or basal cell
    skin cancer.
    19. Any severe and/or controlled medical conditions which could cause unacceptable safety risks or compromise compliance with the protocol, such as:
    a) ≥Grade 3 hypercholesterolemia/hypertriglyceridemia or ≥Grade 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment if given)
    b) Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug (e.g ulcerative disease, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome).
    c) active skin, mucosa, ocular or GI disorders of Grade >1
    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 appproximately 12 weeks later (and no sooner than 8 weeks later).
    In addition, response requires that:
    • the non-target SEGA lesions have not unequivocally worsened
    • no new SEGA lesions (of ≥1cm in longest diameter) are identified
    • and the absence of new or worsening hydrocephalus, (defined by central radiological assessment of ventricular configuration changes, ventricular cap signs
    (periventricular edema) and qualitative assessment of cerebrospinal fluid (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
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    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 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 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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 years4
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months9
    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 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. of subjects incapable of giving consent
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 42
    F.4.2.2In the whole clinical trial 99
    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)
    Patients will continue to be treated per normal standard of 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 Decision2009-09-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-09-15
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-10-02
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