Uveitis
Conditions
Keywords
Active uveitis, intermediate uveitis, panuveitis, posterior uveitis, uveitis
Brief summary
This study will assess the safety and efficacy of AIN457 as adjunctive therapy for the treatment of intermediate uveitis, posterior uveitis, or panuveitis requiring systemic immunosuppression.
Interventions
DRUGAIN457
DRUGPlacebo
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
* Male and female subjects ≥18 years of age. Where relevant, parents will also sign the informed consent according to local laws and regulations * Patients with diagnosis of chronic non-infectious intermediate uveitis, posterior uveitis or panuveitis in at least one eye * Evidence of active intermediate, posterior or panuveitis (grade ≥ 2+ vitreous haze with or without the presence of anterior chamber cells) at screening and baseline in at least one eye * Requirement for any of the following immunosuppressive therapies for the treatment or prevention of uveitis: * Prednisone or equivalent ≥10 mg daily at any time within the past 3 months. * ≥1 periocular injection or ≥1 intravitreal corticosteroid injection (e.g. triamcinolone) in the study eye within the past 6 months (the last injection must not have been given 6 weeks prior to screening). * Treatment with either cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate at any time within the past 3 months (Patients treated with chlorambucil or cyclophosphamide within the past 5 years are ineligible for the study). * Patients not meeting the above specified criteria for immunosuppressive therapies are eligible for enrollment if they are intolerant to systemic immunosuppressive therapy as determined by the study investigator. * Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed
Exclusion criteria
Ocular concomitant conditions/disease * Patients receiving or that may require prednisone (or equivalent) ≥1.5 mg/kg/day for the treatment of their active uveitis * Patients with a primary diagnosis of Behcet's disease, anterior uveitis or any intermediate uveitis, posterior uveitis or panuveitis in which the manifestation(s) of the active intraocular inflammatory disease may spontaneously resolve or that are not characterized by the presence of either anterior chamber cells or vitritis (vitreous cell and haze) such as the white dot retino-choroidopathies (i.e. Punctate inner choroidopathy (PIC), acute zonal occult outer retinopathy (AZOOR) * Patients with infectious uveitis or uveitis of an underlying diagnosis that is uncertain and would reasonably include a disease for which immunosuppression would be contraindicated (e.g. ocular lymphoma) Ocular treatments * Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening * Treatment with fluocinolone acetonide implant in the study eye within the last 3 years, or dexamethasone intravitreal implant and any other investigational corticosteroid implants in the study eye within the last 6 months. * 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 * Ocular disease that would interfere with ocular evaluations (e.g. corneal scarring, cataract, vitreous hemorrhage) or that in the opinion of the investigator would complicate the evaluation of the safety or efficacy of the study treatment (e.g. uncontrolled glaucoma, toxoplasma scar, macular scarring) * 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, etc.) Systemic conditions or treatments * Any previous treatment with AIN457 * Any systemic biologic therapy (e.g. interferon, infliximab, daclizumab, etanercept, or adalimumab) given intravenously or subcutaneously within 3 months prior to screening. No biologic therapy other than the investigational study treatment will be allowed during the course of the clinical trial * Any prior treatment with systemic alkylating agents (cyclophosphamide, chlorambucil) within the past 5 years prior to screening * Treatment with any live or live-attenuated vaccine (including vaccine for varicella-zoster or measles) within 2 months prior to screening. No treatment with live or live-attenuated vaccines will be allowed during the course of the clinical trial Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Vitreous Haze Grade in the Study Eye From Baseline to 28 Weeks or at Time of Rescue, if Earlier. | baseline to 28 weeks | No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Responders With no Recurrence of Active Intermediate, Posterior, or Panuveitis in the Study Eye at 28 Weeks | baseline to 28 weeks | No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided. |
| Mean Change in Best Corrected Visual Acuity From Baseline to 28 Weeks | baseline to 28 weeks | No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided. |
| Change From Baseline in Quality of Life/Patient Reported Outcome Assessments | baseline to 28 weeks | No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided. |
| Mean Change in Vitreous Haze Grade and Anterior Chamber Cell Grade From Baseline to 28 Weeks | baseline to 28 weeks | No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided. |
| Change in Immunosuppressive Medication Score From Baseline to Week 28 | baseline to 28 weeks | No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided. |
Countries
Canada, Egypt, France, Germany, Hungary, India, Israel, Japan, Singapore, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Disposition of the 31 randomized patients is summarized in the table below. As a consequence of the early termination, few patients (N=31) were randomized into this study. Of these, 30 patients were discontinued due to administrative reasons (30 patients due to study termination and also one due to misrandomization). One patient withdrew consent.
Pre-assignment details
As a consequence of the early termination, few patients (N=31) were randomized into this study. Of these, 30 patients were discontinued due to administrative reasons (30 patients due to study termination, including one due to misrandomization. One patient withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| AIN457 300mg s.c Every 2 Weeks AIN457 300 mg subcutaneously at baseline, Week 1 and Week 2, then every 2 weeks | 8 |
| AIN457 300mg s.c. Every 4 Weeks AIN457 300 mg subcutaneously at baseline and Week 2, then every 4 weeks. | 10 |
| AIN457 150mg s.c Every 4 Weeks AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks | 8 |
| Placebo s.c Every 2 Weeks Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks | 5 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | administrative reasons | 8 | 10 | 7 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | AIN457 300mg s.c Every 2 Weeks | AIN457 300mg s.c. Every 4 Weeks | AIN457 150mg s.c Every 4 Weeks | Placebo s.c Every 2 Weeks | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.5 Years STANDARD_DEVIATION 21.13 | 46.9 Years STANDARD_DEVIATION 12.8 | 44.6 Years STANDARD_DEVIATION 15.99 | 50.6 Years STANDARD_DEVIATION 12.99 | 47.1 Years STANDARD_DEVIATION 15.47 |
| Region of Enrollment Canada | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Region of Enrollment France | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Germany | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Hungary | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Israel | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Japan | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 13 Participants |
| Region of Enrollment Singapore | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Switzerland | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 2 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 6 Participants | 2 Participants | 16 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 | 6 / 8 | 4 / 10 | 6 / 8 | 4 / 4 |
| serious Total, serious adverse events | 1 / 8 | 1 / 10 | 0 / 8 | 0 / 4 |
Outcome results
Primary
Mean Change in Vitreous Haze Grade in the Study Eye From Baseline to 28 Weeks or at Time of Rescue, if Earlier.
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Population: The results of Study CAIN457C2303 did not meet the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.
Secondary
Change From Baseline in Quality of Life/Patient Reported Outcome Assessments
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Secondary
Change in Immunosuppressive Medication Score From Baseline to Week 28
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Secondary
Mean Change in Best Corrected Visual Acuity From Baseline to 28 Weeks
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Secondary
Mean Change in Vitreous Haze Grade and Anterior Chamber Cell Grade From Baseline to 28 Weeks
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks
Secondary
Proportion of Responders With no Recurrence of Active Intermediate, Posterior, or Panuveitis in the Study Eye at 28 Weeks
No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.
Time frame: baseline to 28 weeks