E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033687 |
E.1.2 | Term | Panuveitis |
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E.1.3 | Condition being studied is a rare disease | No |
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 the suppression of intraocular inflammation and the prevention of an active intermediate, posterior or panuveitis recurrence during the withdrawal of concomitant immunosuppressive therapy in adults with quiescent, non-infectious, uveitis affecting the posterior segment in Group 1. |
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E.2.2 | Secondary objectives of the trial |
Key secondary: To determine if continuous treatment with subcutaneous AIN457 can reduce the need for standard-of-care immunosuppressive medications in Group 1 patients requiring systemic immunosuppression to control their ocular inflammatory disease. See original Protocol Chapter 3. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for Group 1: 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. Inclusion criteria for Group 2: 1. Patients who were randomized into the 24-week core study and did not complete the treatment period or will not continue treatment in the extension phase. |
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E.4 | Principal exclusion criteria |
Exclusion criteria for Group 1: 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. There are no Exclusion criteria for Group 2. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the efficacy of continuous treatment with subcutaneous AIN457 compared to placebo for maintaining the suppression of intraocular inflammation and the prevention of an active intermediate, posterior or panuveitis recurrence during the withdrawal of concomitant immunosuppressive therapy in adults with quiescent, non-infectious, uveitis affecting the posterior segment in Group 1. H3: There is no difference in the proportion of patients with 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 proportion of patients with recurrence during the combined core and extension phase in favor of the core AIN457 dose regimen). The treatment difference will be analyzed using logistic regression with proportion of patients with recurrence during the combined core and extension phase as dependent variable, treatment, the stratification variables country (or region) and core baseline total immunosuppressive score level (≤5 or >5) as factors. For patients who early discontinue the extension phase and do not have a recurrence during either the core or extension phase, the event of recurrence will be imputed using the same method described in Section 9.4.2 of core protocol [CAIN457C2301]. The primary analysis population for the confirmatory testing of the hypotheses will be the FAS. Multiplicity adjustment for the primary and key secondary efficacy variables will be performed as described in Section 9.5.1.3 of core protocol [CAIN457C2301]. |
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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 | 5 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |