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    Summary
    EudraCT Number:2009-014835-19
    Sponsor's Protocol Code Number:CAIN457C2301
    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:2010-03-17
    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 ConcernedUK - MHRA
    A.2EudraCT number2009-014835-19
    A.3Full title of the trial
    A 24-week multicenter, randomized, double-masked, placebo controlled, dose-ranging phase III study of AIN457 versus placebo for maintaining uveitis suppression when reducing systemic immunosuppression in patients with quiescent, non-infectious intermediate, posterior or panuveitis (ENDURE Study)
    A.3.2Name or abbreviated title of the trial where available
    ENDURE, C2301
    A.4.1Sponsor's protocol code numberCAIN457C2301
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) Numbernot available
    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 nameAIN457
    D.3.2Product code AIN457
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.11 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 Yes
    D.3.11.13.1Other medicinal product typeRecombinant human monoclonal antibody to Interleukin-17A of the IgG1/kappa class
    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 placeboPowder for solution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Demonstrate the efficacy and safety of AIN457 as adjunctive therapy for the treatment of intermediate uveitis, posterior uveitis or panuveitis requiring systemic immunosuppression
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10022941
    E.1.2Term Iridocyclitis
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The purpose of this study is to determine whether, in patients with quiescent, non-infectious, intermediate, posterior uveitis or panuveitis, AIN457 maintains the suppression of intraocular inflammation and prevents active uveitis recurrence during the withdrawal of concomitant immunosuppressive therapy, when compared to placebo. Both AIN457 and placebo will be administered adjunctive to standard-of-care therapy systemic immunosuppressive therapy.
    An add-on design was chosen because, due to risk of vision loss that may occur during a recurrence of active uveitis, it would be unethical to compare AIN457 to placebo without any additional immunosuppressive treatment. Despite concurrent administration of standard-of-care immunosuppressive therapy it is expected that a clear treatment benefit of AIN457 over placebo can be shown.
    E.2.2Secondary objectives of the trial
    • Key secondary objective: To determine if treatment with subcutaneous AIN457 can reduce or eliminate the need for standard-of-care immunosuppressive medications
    • To assess the safety of targeted IL-17 inhibition with AIN457 in patients with quiescent uveitis affecting the posterior segment requiring standard-of-care immunosuppression
    • To evaluate the effect of subcutaneous AIN457 on visual acuity and quality of life when used as an adjunctive immunomodulatory therapy to standard-of-care immunosuppressive treatment
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients eligible for inclusion in this study have to fulfill all of the following criteria:
    1. Male and female subjects ≥18 years of age
    2. Patients with quiescent chronic, non-infectious intermediate uveitis, posterior uveitis or panuveitis as evidenced by <1+ anterior chamber cell grade and <1+ vitreous haze in both eyes for at least 6 weeks prior to screening
    3. Requirement for either of the following immunosuppressive therapies at any time within the past 3 months for the treatment or prevention of uveitis which must not have been increased within the 6 weeks prior to screening:
    • Prednisone or equivalent ≥10 mg daily
    • ≥1 periocular injection or ≥1 intravitreal corticosteroid injection (i.e. triamcinolone) in the study eye within the past 6 months (the last injection must not have been given 6 weeks prior to screening)
    • Treatment with either cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate as monotherapy or in combination with or without steroids. (Patients treated with chlorambucil or cyclophosphamide within the past 5 years are ineligible for the study)
    • Patients not meeting the above specified criteria for immunosuppressive therapies are eligible for enrollment if they are intolerant to systemic immunosuppressive therapy as determined by the study investigator
    4. Patients must be willing to be weaned from their current systemic immunosuppressive therapy.
    5. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed
    E.4Principal exclusion criteria
    1. Patients with a primary diagnosis of Behcet’s disease, anterior uveitis or any intermediate uveitis, posterior uveitis or panuveitis in which the manifestation(s) of the active intraocular inflammatory disease may spontaneously resolve or that are not characterized by the presence of either anterior chamber cells or vitritis (vitreous cell and haze) such as the white dot retino-choroidopathies (i.e. Punctate inner choroidopathy (PIC), acute zonal occult outer retinopathy (AZOOR)
    2. Patients with active, non-infectious intermediate, posterior or panuveitis in one or both eyes (≥1+ anterior chamber cells and /or ≥1+ vitreous haze)
    3. Patients receiving or that may require corticosteroids (prednisone or equivalent) ≥1 mg/kg/day to maintain quiescence of their intraocular inflammation.
    4. Patients with infectious uveitis or uveitis of an underlying diagnosis that is uncertain and would reasonably include a disease for which immunosuppression would be contraindicated (i.e. ocular lymphoma).
    5. Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening.
    6. Treatment with fluocinolone acetonide implant (Retisert®) in the study eye within the last 3 years, or dexamethasone intravitreal implant and any other investigational corticosteroid implants in the study eye within the last 6 months.
    7. Intraocular surgery or laser photocoagulation in the study eye within the last 6 weeks prior to screening except for a diagnostic vitreous or aqueous tap with a small-gauge needle.
    8. Planned elective ocular surgery during the study.
    9. Ocular disease that would interfere with ocular evaluations (e.g. corneal scarring, cataract, vitreous hemorrhage) or that in the opinion of the investigator would complicate the evaluation of the safety or efficacy of the study treatment (i.e. uncontrolled glaucoma, toxoplasma scar, macular scarring).
    10. Current use of or likely need for systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine, ethambutol, etc.)
    Systemic conditions or treatments
    11. Any previous treatment with AIN457
    12. Any systemic biologic therapy (e.g. interferon, infliximab, daclizumab, etanercept, or adalimumab) given intravenously or subcutaneously within 3 months prior to screening. No biologic therapy other than the investigational study treatment will be allowed during the course of the clinical trial.
    13. Any prior treatment with systemic alkylating agents (cyclophosphamide, chlorambucil) within the past 5 years prior to screening.
    14. Treatment with any live or live-attenuated vaccine (including vaccine for varicella-zoster or measles) within 2 months prior to screening. No treatment with live or live-attenuated vaccines will be allowed during the course of the clinical trial.
    15. Active systemic infections during the last two weeks prior to screening (exception: common cold)
    16. Underlying metabolic, hematologic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patients and/or places the patient at an unacceptable risk for participation in an immunomodulatory therapy.
    17. Systemic or extraocular disease that would contraindicate long-term immunosuppression, especially infectious diseases such as:
    • any active, chronic or localized infection
    • a history of an infectious disease that can spontaneously re-emerge or that are impossible to completely cure, such as histoplasmosis, toxoplasmosis, malaria, viral hepatitis, and HIV/AIDS
    • history of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by either a positive PPD skin test or a positive QuantiFERON TB-Gold test. Patients with evidence of latent tuberculosis may enter the trial after evaluation by a appropriate specialist and after sufficient treatment has been initiated according to local regulations
    18. History of lymphoproliferative disease or any known malignancy or history of malignancy within the past 5 years of any organ system, treated or untreated, whether or not there is evidence of local recurrence or metastases (except for non-melanoma skin cancer that has been treated with no evidence or recurrence in the past 3 months, carcinoma in situ of the cervix or colon polyps with non-invasive malignancy that have been removed).
    19. History of ongoing drug or alcohol abuse within the 6 months prior to screening or clinical evidence of such abuse or clinical suspicion of such abuse.
    20. Any medical or psychiatric condition which, in the investigator’s opinion would preclude the participant from adhering to the protocol or completing the study per protocol.
    E.5 End points
    E.5.1Primary end point(s)
    In the proposed 24-week multi-center, double masked, placebo controlled core study patients with quiescent chronic, non-infectious intermediate uveitis, posterior uveitis or panuveitis requiring systemic immunosuppressive therapy will be randomized to one of three subcutaneous injections dose regimens of AIN457 or placebo and followed to the determine the effect and safety of the AIN457 for maintaining suppression of intraocular inflammation while concomitant immunosuppressive medications are gradually withdrawn. The primary research hypothesis is to determine if inhibition of IL-17 by AIN457 can block a central stimulus to the propagation of the autoimmune cascade suggested to play a role in the development of uveitis thereby maintaining suppression of the disease and preventing an active recurrence during the withdrawal of concomitant immunosuppressive treatment and as a result preserving vision and improving quality of life.
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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.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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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 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
    After completion of the 24 week core treatment period all patients will enter the extension study AIN457C2301E1 and consent to either an additional 26 week treatment or a 12 week treatment-free follow-up period
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months12
    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 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 2010-03-17. 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 state36
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 340
    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 Decision2010-01-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-03-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-06-06
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