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 patients with quiescent, non-infectious intermediate, posterior or panuveitis |
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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 | 10022941 |
E.1.2 | Term | Iridocyclitis |
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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 |
To evaluate the efficacy of continuous treatment with subcutaneous AIN457 compared to placebo for maintaining quiescence of intraocular inflammation and the prevention of active intermediate, posterior or panuveitis recurrences in adults with quiescent, non-infectious uveitis affecting the posterior segment. |
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E.2.2 | Secondary objectives of the trial |
•to determine if continuous treatment with subcutaneous AIN457 can reduce/eliminate the need for concomittant standard-of-care immunosuppressive medications in patients •to assess safety of continuous targeted IL-17 inhibition with AIN457 in patients over 1 year •to determine the effect of continuous treatment with subcutaneous AIN457 on visual acuity, vitreous haze, anterior chamber celles and quality of life in patients • to explore the relative benefit of 3 dose regimens of AIN457 given over 1 year in patients •to allow for an adequate safety follow up (12 weeks post-study treatment) in patients prematurely discontinuing or completing study treatment in the extension study |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who have completed the entire treatment period of the 24 week core study 2. Patients 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 |
1. Inability or unwillingness to undergo repeated subcutaneous injections 2. Inability to comply with study or follow-up procedures. 3. 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. 4. 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 hCG laboratory test (> 5 mIU/mL) 5. 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, condom plus spermicidal gel, 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 and for 16 weeks after study drug discontinuation. [Note: Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods), spermicides alone without condoms or cervical caps and withdrawal are not considered acceptable methods of contraception.] • They are postmenopausal with an appropriate clinical profile (e.g, age appropriate, history of vasomotor symptoms) and had no regular menstrual bleeding for at least twelve (12) months prior to initial dosing. Menopause must be confirmed by a plasma FSH level of >40 IU/L at screening • They have undergone reliable surgical 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. • Their career, lifestyle, or sexual orientation precludes intercourse with a male partner • Partners have been sterilized by vasectomy or other reliable means 6. Male subjects must agree to use simultaneously two acceptable methods of contraception (e.g. condom plus spermicidal gel) 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 or withdrawal are not acceptably adequate methods of contraception. Reliable contraception must 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 objective of the study is to evaluate the efficacy of continuous treatment with subcutaneous AIN457 compared to placebo for maintaining the suppression of intraocular inflammation and the prevention of active intermediate, posterior or panuveitis recurrences in adults with non-infectious uveitis affecting the posterior segment. The primary analysis will take all data of the combined core and extension study into account based on the FAS. The primary null hypotheses to be tested are the following: H1: There is no difference in the rate of recurrence during the combined core and extension phase between patients treated with AIN457 300 mg every 2 weeks and placebo H2: There is no difference in the rate of recurrence during the combined core and extension phase between patients treated with AIN457 300 mg every 4 weeks and placebo H3: There is no difference in the rate of recurrence during the combined core and extension phase between patients treated with AIN457 150 mg every 4 weeks and placebo (versus the one-sided alternative hypothesis for each core AIN457 dose regimen that there is a difference in the rate of recurrence during the combined core and extension phase in favor of the core AIN457 dose regimen).
The statistical hypothesis testing will be based on the analysis of the ordered categorical data based on the rounded annualized number of recurrences by the use of a proportional odds model using treatment group and the stratification variable baseline immunosuppressive medication score as covariante. If the proportion of patients with high number of recurrences is larger than anticipated, additional categories for the annualized number of recurrences may be considered. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |