Safety and Efficacy of AIN457 in Patients With Quiescent Non-infectious Uveitis

Study Overview
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Brief Summary
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This extension study will assess the safety and efficacy of AIN457 versus placebo for maintaining uveitis suppression when reducing systemic immunosuppression

Official Title
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A 38-week Extension to 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

Conditions
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Non-infectious Uveitis

Intervention / Treatment
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* Drug: AIN457
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have completed the entire treatment period of the 24 week core study Exclusion Criteria: Inability or unwillingness to undergo repeated subcutaneous injections; inability to comply with study or follow-up procedures; any medical or psychiatric condition which, in the investigator's opinion wouldpreclude the participant from adhering to the protocol or completing the study per protocol. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AIN457 300mg every 2 weeks<br>AIN457 300 mg subcutaneous (s.c.) weekly for 3 weeks followed by AIN457 300 mg s.c. every 2 weeks | Drug: AIN457<br>* AIN457 150 mg powder for solution was provided in glass vials each containing 150 mg AIN457 as a lyophilized cake<br>|
| Experimental: AIN457 300 mg every 4 weeks<br>AIN457 300 mg s.c. at baseline for Week 2 followed by AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly | Drug: AIN457<br>* AIN457 150 mg powder for solution was provided in glass vials each containing 150 mg AIN457 as a lyophilized cake<br>|
| Experimental: AIN457 150 mg every 4 weeks<br>AIN457 150 mg s.c. and placebo s.c. at Baseline and Week 2 followed by AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly | Drug: AIN457<br>* AIN457 150 mg powder for solution was provided in glass vials each containing 150 mg AIN457 as a lyophilized cake<br>|
| Placebo Comparator: Placebo<br>Placebo s.c. every 2 weeks | Drug: Placebo<br>* Matching placebo to AIN457<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Time to the First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline | Kaplan-Meier estimates for the time to the first recurrence in any eye of active intermediate, posterior, or panuveitis from baseline defined by either: ≥ 2 step increase in vitreous haze with or without an increase in anterior chamber cell grade or decrease in best corrected visual acuity, core and extension | Baseline to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | The changes in steps (0, 1, or >= 2) from previous visit for vitreous haze, where the score is evaluated based on NEI Vitreous Haze Grading Scale (0 -4). Vitreous haze was recorded as 0-clear; to 4+ as dense opacity obscuring the optic nerve head. A 1 step increase is defined as any of the following changes: 0-1, 0.5-1, 1-2, 2-3, 3-4. A 2 step increase is defined as any of the following changes: 0-2, 0.5-2, 1-3, 2-4. A recurrent episode of active intermediate, posterior or panuveitis was considered to be resolved, if the eye returns and maintains in a quiescent state (<1+ anterior chamber cell grade and <1+ vitreous haze) for at least 2 weeks | Baseline to 52 weeks | 
| Mean Change in Best Corrected Visual Acuity From Baseline, Core and Extension | The Best Corrected Visual Acuity (BCVA) is tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) testing protocol. VA measurements are taken in a sitting position at an initial test distance of 4 meters using ETDRS charts. The overall BCVA score is calculated using the BCVA worksheet 0-100 letter score | Baseline to 52 weeks | 
| Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies | Evaluation of recurrence until resolution is ascertained, based on the first criteria (a >2 step increase in vitreous haze with or without an increase in anterior chamber cell grade in either eye). A 2 step increase is defined as any of the following changes: 0-2, 0.5-2, 1-3, 2-4 | Baseline to 52 weeks | 
| Composite Immunosuppressive Medication Score From Baseline to Week 52, Core and Extension | IMS is a combined, single numeric score derived on the basis of the total daily dose of specific immunosuppressive agents per unit body weight, ranged on a scale from 0 to 9 for the total daily dose in milligrams per kilogram. The total IMS is the sum of the scores derived for the agents included into the score. The treatment groups will be compared using an analysis of covariance with treatment, region, and baseline IMS as covariate. The total IMS is the sum of scores derived from the agents included into the score, and ranged from 0 to 55. Treatment groups compared using analysis of covariance with treatment & baseline IMS as covariate, where the lower IMS showed better clinical outcome. | Baseline to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Quiescent uveitis, intermediate uveitis, panuveitis, posterior uveitis, uveitis, NVS Definition: Words or phrases that best describe the protocol. Keywords help users find studies in the database., Avoid acronyms, abbreviations and trade names., Examples: Heart failure, aliskiren, heart attack, cardiovascular diseases, Psoriasis, inflammatory skin disease, scaly patches