E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adjunctive therapy to standard-of-care for the treatment of posterior uveitis or panuveitis secondary to Behçet's disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033687 |
E.1.2 | Term | Panuveitis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036370 |
E.1.2 | Term | Posterior uveitis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Main objective:
To determine the efficacy of subcutaneous AIN457 compared to placebo in reducing the rate of recurrent ocular exacerbations in Behçet’s patients with posterior uveitis or panuveitis who are receiving standard-of-care immunomodulatory therapy. |
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E.2.2 | Secondary objectives of the trial |
objectives: - Determine if subcutaneous AIN457 reduces need for standard-of-care immunosuppressive medications in patients requiring systemic immunosuppression to treat or prevent posterior uveitis or panuveitis secondary to Behçet’s disease. - Assess safety of targeted IL-17 inhibition with AIN457 in patients with posterior or panuveitis secondary to Behçet’s disease receiving standard-of-care immunomodulatory therapy - To determine the effect of subcutaneous AIN457 on macular edema and visual acuity . - To establish the impact of AIN457 on quality of life. - To observe the effect of AIN457 on the systemic non-ocular manifestations of Behçet’s disease. - To observe the effect of AIN457 on retinal vascular leakage and macular edema as determined by fluorescein angiography
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male and female subjects >18 years of age 2.Patients with Behçet’s disease and with a history of recurrent uveitis in a least one eye. Patients with both active (experiencing an acute exacerbation) and quiescent (in between exacerbations) intermediate, posterior uveitis or panuveitis secondary to Behçet’s disease at the time of screening are eligible for the study. The diagnosis of Behçet’s disease lies in the judgment of the investigator. 3.Documented evidence of >2 recurrent exacerbations of either intermediate, posterior uveitis or panuveitis in the study eye within the past 6 months (this could include the current exacerbation for patients having an acute exacerbation at enrollment). Exacerbations fulfilling the study inclusion criteria must have one or more of the following recorded in the patients medical record for each recurrent exacerbation: >2+ vitreous haze score with <2+ anterior chamber cell grade (intermediate or posterior uveitis) or >2+ vitreous haze score with >2+ anterior chamber cell grade (panuveitis) presence of retinal infiltrates or vasculitis or hemorrhages documented >10 ETDRS letter or 2 line Snellen decrease in visual acuity attributed to ocular inflammation secondary to the recurrent exacerbation of Behçet’s disease. 4.Requirement for either of the following immunosuppressive therapies for at least 3 of the past 6 months for the treatment of or to prevent an exacerbation of ocular inflammation related to Behçet’s disease Prednisone or equivalent > or = 10 mg daily The need for at least > or = 1 periocular injection or > or = 1 intravitreal corticosteroid injection in the study eye within the past 6 months (the last injection must not been given within 6 weeks of screening) Treatment with cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid or methotrexate either as monotherapy or in combination with or without steroids. (Patients treated at any time with chlorambucil or cyclophosphamide are not eligible for the study.) Patients not meeting the above specified criteria for immunosuppressive therapies are eligible for the study if they are intolerant to systemic immunosuppressive therapy as determined by the study investigator 5.Patient must be able to understand and communicate with the investigator and comply with the requirements for the study and must give a written, signed, and dated informed consent before any study assessment is performed.
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E.4 | Principal exclusion criteria |
-Ocular concomitant conditions/disease Subjects with infectious uveitis, uveitis due to other causes than Behçet’s disease, or uveitis of unknown etiology. Less severe (i.e. anterior) uveitis associated with Behçet’s disease -Ocular treatments for instance : with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening ; with any injected or implantable corticosteroid releasing device (i.e. fluocinolone acetonide implant, Retisert®) in the study eye within the last 3 years ; 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; 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) -Systemic conditions or treatments, for instance : Treatment with any live or live-attenuated vaccine (including vaccine for varicella-zoster virus or measles) within 2 months prior to screening. Any systemic biologic therapy (e.g. interferon, infliximab, daclizumab, etanercept, or adalimumab) given intravenously or subcutaneously within 3 months prior to screening and no prior treatment with AIN457. Any prior treatment with systemic alkylating agents (cyclophosphamide, chlorambucil). Active systemic infections during the last two weeks (exception : common cold) prior screening. Underlying metabolic, hematologic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at an unacceptable risk for participation in an immunomodulatory therapy. Any comorbid disease that would contraindicate long-term immunosuppression, especially infectious diseases. -Compliance/Administrative, for instance : Inability or unwillingness to undergo repeated subcutaneous injections Inability or unwillingness to receive treatment with oral corticosteroids if recommended by the study investigator. Participation in any other clinical investigation within 4 weeks prior to screening (or longer if required by local regulations), and for any other limitation of participation based on local regulations. Pregnant or nursing ( lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum pregnancy test (hCG>5mIU/ml) Women of childbearing potential (WoCBP), defined as all women physiologically capable of becoming pregnant, UNLESS they are: Using simultaneously double barrier or two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc., hormone replacement as either oral or implantable is acceptable as one form), from the time of screening and for the duration of the study, through study completion. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. They are postmenopausal and had no regular menstrual bleeding for at least two (2) years prior to initial dosing. Menopause must be confirmed by a plasma FSH level of >40 IU/L at screening They have undergone surgically sterilization at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and/or Principal Investigator and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. They have male partners who have undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing. 24. Male subjects UNLESS they use simultaneously two acceptable methods of contraception (e.g. spermicidal gel plus condom) for the entire duration of the study, up to the study completion visit, unless they have undergone a vasectomy more than six (6) months prior to first dosing. A vasectomy must be supported with clinical documentation made available to the sponsor and/or Principal Investigator and noted in the Relevant Medical History/ Current Medical Conditions sections of the CRF. Periodic abstinence and withdrawal are not acceptably adequate methods of contraception. Reliable contraception should be maintained in men and women throughout the study and for 16 weeks after study drug discontinuation. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the rate of recurrent ocular exacerbations of posterior uveitis or panuveitis in the study eye during the 24 weeks of study treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and health related quality of life |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial 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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial months | 9 |