Non-infectious Uveitis
Conditions
Keywords
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
Brief summary
This extension study will assess the safety and efficacy of AIN457 versus placebo for maintaining uveitis suppression when reducing systemic immunosuppression
Interventions
DRUGAIN457
AIN457 150 mg powder for solution was provided in glass vials each containing 150 mg AIN457 as a lyophilized cake
DRUGPlacebo
Matching placebo to AIN457
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Time to the First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline | Baseline to 52 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | Baseline to 52 weeks | 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 |
| Mean Change in Best Corrected Visual Acuity From Baseline, Core and Extension | Baseline to 52 weeks | 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 |
| Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies | Baseline to 52 weeks | 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 |
| Composite Immunosuppressive Medication Score From Baseline to Week 52, Core and Extension | Baseline to 52 weeks | 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. |
Countries
Brazil, Germany, India, Israel, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Between August 2010 and March 2011, 70 patients were enrolled from 51 centers in 9 countries (United States, Germany, Switzerland, India, Spain, United Kingdom, Israel, Brazil, Italy). Recruitment was stopped due to study termination, therefore 16 out of 86 patients signed informed consent while being in core study were not enrolled into extension
Pre-assignment details
In total, 125 patients were randomized to the core study with 1 patient misrandomized. Of these 124 patients 70 patients entered the extension period of the study. Core study NCT01032915
Participants by arm
| Arm | Count |
|---|---|
| AIN457 300mg Every 2 Weeks AIN457 300 mg s.c. every 2 weeks | 29 |
| AIN457 300 mg Every 4 Weeks AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly | 31 |
| AIN457 150 mg Every 4 Weeks AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly | 31 |
| Placebo Placebo s.c. every 2 weeks | 34 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Core Study | Abnormal test procedure result | 0 | 0 | 1 | 0 |
| Core Study | Administrative reasons | 5 | 6 | 4 | 4 |
| Core Study | Adverse Event | 2 | 2 | 1 | 1 |
| Core Study | Protocol deviation | 1 | 0 | 0 | 1 |
| Core Study | Subject withdrew consent | 0 | 3 | 1 | 1 |
| Extension Study | Adverse Event | 0 | 0 | 0 | 1 |
| Extension Study | Aministrative problems | 13 | 15 | 14 | 18 |
| Extension Study | Subject withdrew consent | 0 | 1 | 0 | 0 |
| Extension Study | Unsatisfactory therapeutic effect | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | AIN457 300mg Every 2 Weeks | AIN457 300 mg Every 4 Weeks | AIN457 150 mg Every 4 Weeks | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 46.2 Years STANDARD_DEVIATION 14.29 | 49.2 Years STANDARD_DEVIATION 11.14 | 47.7 Years STANDARD_DEVIATION 13.5 | 47.3 Years STANDARD_DEVIATION 15.46 | 47.6 Years STANDARD_DEVIATION 13.6 |
| Sex: Female, Male Female | 17 Participants | 16 Participants | 20 Participants | 18 Participants | 71 Participants |
| Sex: Female, Male Male | 12 Participants | 15 Participants | 11 Participants | 16 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 29 | 19 / 31 | 22 / 31 | 22 / 33 |
| serious Total, serious adverse events | 4 / 29 | 1 / 31 | 1 / 31 | 2 / 33 |
Outcome results
Primary
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
Time frame: Baseline to 52 weeks
Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AIN457 300mg Every 2 Weeks | The Time to the First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline | NA Days |
| AIN457 300 mg Every 4 Weeks | The Time to the First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline | NA Days |
| AIN457 150 mg Every 4 Weeks | The Time to the First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline | NA Days |
| Placebo | The Time to the First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline | NA Days |
Secondary
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
Time frame: Baseline to 52 weeks
Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AIN457 300mg Every 2 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 1 step decrease | 0 Number of participants |
| AIN457 300mg Every 2 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 1 step increase | 4 Number of participants |
| AIN457 300mg Every 2 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 2 or more steps decrease | 0 Number of participants |
| AIN457 300mg Every 2 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | No changes | 21 Number of participants |
| AIN457 300mg Every 2 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 2 or more steps increase | 4 Number of participants |
| AIN457 300 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | No changes | 21 Number of participants |
| AIN457 300 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 1 step decrease | 0 Number of participants |
| AIN457 300 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 2 or more steps decrease | 0 Number of participants |
| AIN457 300 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 1 step increase | 8 Number of participants |
| AIN457 300 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 2 or more steps increase | 2 Number of participants |
| AIN457 150 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | No changes | 23 Number of participants |
| AIN457 150 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 2 or more steps increase | 1 Number of participants |
| AIN457 150 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 1 step increase | 7 Number of participants |
| AIN457 150 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 1 step decrease | 0 Number of participants |
| AIN457 150 mg Every 4 Weeks | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 2 or more steps decrease | 0 Number of participants |
| Placebo | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 1 step decrease | 0 Number of participants |
| Placebo | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 1 step increase | 11 Number of participants |
| Placebo | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 2 or more steps increase | 2 Number of participants |
| Placebo | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | No changes | 20 Number of participants |
| Placebo | Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value | 2 or more steps decrease | 0 Number of participants |
Secondary
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.
Time frame: Baseline to 52 weeks
Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIN457 300mg Every 2 Weeks | Composite Immunosuppressive Medication Score From Baseline to Week 52, Core and Extension | -5.67 Units on a scale | Standard Deviation 4.163 |
| AIN457 150 mg Every 4 Weeks | Composite Immunosuppressive Medication Score From Baseline to Week 52, Core and Extension | -1 Units on a scale | — |
| Placebo | Composite Immunosuppressive Medication Score From Baseline to Week 52, Core and Extension | -1 Units on a scale | — |
Secondary
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
Time frame: Baseline to 52 weeks
Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIN457 300mg Every 2 Weeks | Mean Change in Best Corrected Visual Acuity From Baseline, Core and Extension | 9 Letters | Standard Deviation 4.36 |
| AIN457 150 mg Every 4 Weeks | Mean Change in Best Corrected Visual Acuity From Baseline, Core and Extension | 16 Letters | — |
| Placebo | Mean Change in Best Corrected Visual Acuity From Baseline, Core and Extension | 5 Letters | — |
Secondary
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
Time frame: Baseline to 52 weeks
Population: Full analysis set (FAS): all randomized patients who received at least one dose of study drug in the core study and had at least one post-baseline assessment for the primary efficacy parameter or any of its components. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AIN457 300mg Every 2 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 | Patients with recurrence | 8 Number of participants |
| AIN457 300mg Every 2 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 | Patients with only vitreous haze criterion | 2 Number of participants |
| AIN457 300mg Every 2 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 | Patients with only visual acuity criterion | 5 Number of participants |
| AIN457 300mg Every 2 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 | Both criteria at the same time | 1 Number of participants |
| AIN457 300 mg Every 4 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 | Patients with only vitreous haze criterion | 3 Number of participants |
| AIN457 300 mg Every 4 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 | Patients with only visual acuity criterion | 8 Number of participants |
| AIN457 300 mg Every 4 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 | Both criteria at the same time | 0 Number of participants |
| AIN457 300 mg Every 4 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 | Patients with recurrence | 11 Number of participants |
| AIN457 150 mg Every 4 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 | Patients with only visual acuity criterion | 6 Number of participants |
| AIN457 150 mg Every 4 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 | Patients with only vitreous haze criterion | 4 Number of participants |
| AIN457 150 mg Every 4 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 | Both criteria at the same time | 0 Number of participants |
| AIN457 150 mg Every 4 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 | Patients with recurrence | 10 Number of participants |
| Placebo | Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies | Both criteria at the same time | 0 Number of participants |
| Placebo | Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies | Patients with only vitreous haze criterion | 2 Number of participants |
| Placebo | Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies | Patients with recurrence | 11 Number of participants |
| Placebo | Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies | Patients with only visual acuity criterion | 9 Number of participants |