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    Summary
    EudraCT Number:2010-019825-32
    Sponsor's Protocol Code Number:CRAD001X2201
    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:2010-05-28
    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 number2010-019825-32
    A.3Full title of the trial
    An exploratory, open label, non-randomized, within-patient multiple dose-escalation safety, tolerability, PK and efficacy trial of RAD001 (everolimus) in patients with
    Lymphangioleiomyomatosis
    A.4.1Sponsor's protocol code numberCRAD001X2201
    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 Service 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.3.2Product 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.3.9.2Current sponsor codeRAD001
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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.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 Afinitor
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Ltd
    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.3.2Product 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.3.9.2Current sponsor codeRAD001
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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.IMP: 3
    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 Afinitor
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Ltd
    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.3.2Product 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.3.9.2Current sponsor codeRAD001
    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 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Lymphangioleiomyomatosis
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.1
    E.1.2Level LLT
    E.1.2Classification code 10049459
    E.1.2Term Lymphangioleiomyomatosis
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD, assessed by serum VEGF-D) of everolimus in patients with lymphangioleiomyomatosis (LAM).
    E.2.2Secondary objectives of the trial
    The key secondary objectives are:
    - to assess the clinical efficacy of everolimus as measured by improvement in pulmonary function (FVC).
    - to assess the efficacy of everolimus as measured by improvement in other measures of pulmonary function (FEV-1, lung volumes (TLC, TGV, RV), DLCO).
    - to assess the efficacy of everolimus as measured by improvement in exercise capacity (6-minute walk test), and change in O2 saturation (with supplemental oxygen unchanged).

    For exploratory objectives, please refer to the protocol
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Female aged 18 years or older with a diagnosis of LAM as determined by either of the
    following:
    a. Lung biopsy and chest HRCT scan with findings compatible with LAM or
    b. Typical clinical syndrome and chest HRCT scan findings compatible with LAM
    in plus
    c. one or more of the following:
    ������ CT or histological evidence of renal angiomyolipoma or
    ������ Chylous pleural or abdominal collection or
    ������ Abdominal / pelvic lymphangioleiomyoma or
    ������ Characteristic HRCT scan and clinical syndrome compatible with an
    established genetic diagnosis of tuberous sclerosis complex (using revised
    diagnostic criteria).
    2. Pulmonary function abnormalities as follows:
    a. Forced expiratory volume in one second (FEV1) of ≤ 80% of the predicted value
    following administration of a standard dose of a short acting β2-agonist (*200 μg
    Salbutamol, measured between 10 and 15 minutes of inhalation)
    OR
    b. FEV1 < 90% of the predicted value of bronchodilator following administration of a
    standard dose of a short acting β2-agonist (*200 μg Salbutamol, measured between
    10 and 15 minutes of inhalation) and Dlco (uncorrected) <80% predicted.
    3. Female patients including those of childbearing potential will be included in this
    study. Given this, the following measures to reduce the risk of pregnancy must apply:
    a. Postmenopausal females must have had no regular menstrual bleeding for at least
    one year prior to initial dosing. Menopause will be confirmed by a plasma FSH
    level of >40 IU/L at screening, or
    b. Female patients who report surgical sterilization must have had the procedure at
    least six (6) months prior to initial dosing. Surgical sterilization procedures should
    be supported with clinical documentation made available to the sponsor and noted
    in the Relevant Medical History / Current Medical Conditions section of the CRF,
    or
    c. Two forms of barrier contraception (e.g., condom and occlusive cap plus
    spermicide), or
    d. If female subject has a male partner who has undergone vasectomy, the vasectomy
    must have occurred more than six (6) months prior to first dosing, or
    e. The subject must abstain from vaginal intercourse for the entire duration of the
    study”
    f. The male partners of female patients must refrain from fathering a child for at least
    8 weeks following the last study drug administration.
    4. All female patients must have negative pregnancy test results at screening and at
    baseline
    E.4Principal exclusion criteria
    1. WHO class IV functional status.
    2. FEV1<50% of predicted post-bronchodilator.
    3. Change in FVC (ml) > ± 15% of screening value at baseline visit (not less than 14d
    after screening visit).
    4. Listed for organ transplantation and on active status.
    5. Use of Sirolimus (Rapamycin™) in the 4 months prior to the screening visit and for
    the duration of the study
    6. Use of doxycycline or other tetracycline derivatives within 30 days prior to the
    screening visit and for the duration of the study
    7. Use of an investigational drug within the last 30 days prior to the screening visit
    8. Use of any medicine containing estrogen in the 4 months prior to the screening visit
    and for the duration of the study
    9. Use of alternative or complimentary medications within 30 days prior to the screening
    visit and for the duration of the study
    10. Use of antibiotics or a clinical history consistent with bacterial infection in the 30 days
    prior to study entry
    11. Pregnant or breast feeding
    12. Significant hematologic (Hemoglobin <10mg/dl, White Blood Cell count <3000/ml or
    Absolute Neutrophil Count<1000/ml), renal (creatinine >2 mg/dl) , hepatic laboratory
    abnormality (transaminase levels > three times the upper limit of normal range) or
    amylase > 1.5x the upper limit of the normal range at the screening or baseline visits
    13. Fasting blood glucose > 126mg/dl or random blood glucose >200mg/dl at screening
    and/or baseline
    14. Recent surgery (involving entry into a body cavity or requiring sutures) within 2
    months of the screening visit or any evidence of unhealed surgical wound.
    15. Uncontrolled hyperlipidemia or a history of clinical atherosclerotic disease
    16. Any type of pleural disease severe enough to affect pulmonary function as determined
    by the site investigator.
    17. History of acute pneumothorax or chylothorax within 2 months of the screening visit
    18. Previous organ transplantation
    19. Inability to attend scheduled clinic visits
    20. Inability to give informed consent
    21. Inability to perform pulmonary function or 6 minute walk tests and imaging
    assessments
    22. History of malignancy in the two years prior to the screening visit, other than
    squamous or basal cell skin cancer, angiomyolipoma or menigioma.
    23. Any other reason that the investigator feels that the subject would not be able to
    adequately perform the procedures necessary for study participation or that may put
    patient at risk from participating in the trial.
    24. Contraindications to MRI:
    a. Brain Aneurysm Clip
    b. Implanted neural stimulator
    c. Implanted cardiac pacemaker, pacemaker wires or defibrillator
    d. Prosthetic heart valves
    e. Cochlear implant
    f. Ocular foreign body
    g. Other implanted medical devices
    h. Implanted insulin pump
    i. Metal shrapnel or bullet
    25. BMI > 40 kg/m2 since patients will be difficult to position comfortably inside the MRI
    26. History of immunodeficiency diseases, including a positive HIV test result.
    27. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) test result.
    28. Subjects with a platelet count of <75,000/mm3 will be excluded from the study
    E.5 End points
    E.5.1Primary end point(s)
    Safety and tolerability evaluation (Vital signs and safety measurements)
    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 No
    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.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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 years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    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) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 18
    F.4.2.2In the whole clinical trial 24
    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 Decision2010-06-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-06-10
    P. End of Trial
    P.End of Trial StatusCompleted
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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