Safety and Efficacy of AIN457 in Noninfectious Uveitis
- Registration Number
- NCT00685399
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study was performed to evaluate the efficacy and safety of AIN457 for patients with active uveitis that requires systemic immunosuppression.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 76
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 AIN457 Participants were administered with AIN457 (Sp2/0derived) 10 milligrams per kilogram (mg/kg) intravenous (i.v.) dose on Day 1 and Day 22. Cohort 2 AIN457 Participants were administered with AIN457 (Sp2/0 or Chinese hamster ovary cell (CHO) derived) 10 mg/kg, (CHO derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed a second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3 participants from cohort 1 rolled on into this cohort. Cohort 3 AIN 457 Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22. Cohort 4 AIN 457 Extension period: Participants were administered with AIN457 10 mg/kg, i.v. (with or without a short course of corticosteroids) once a flare had occurred, or periodically at a frequency of not more than once per month at the discretion of the investigator. Cohort 5 AIN457 Participants were administered with AIN457 30 mg/kg single i.v. dose. A second dose was given when all 4 participants completed at least 29 days, and the 30 mg/kg dose was well tolerated by all. Cohort 6 Arm 1 AIN457 Participants were administered with AIN457 300 mg subcutaneously (s.c.) and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43). Cohort 6 Arm 2 AIN 457 Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43). Cohort 6 Arm 3 AIN457 Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died Day 1 to Day 603 AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
- Secondary Outcome Measures
Name Time Method Number of Participants With Remission in Uveitis Baseline (Day 1) up to Month 8 Participants with uveitis who were able to stop all topical and systemic topical corticosteroids in both eyes after the first course of one or two doses by Day 57 visit . The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.
Number of Participants Who Were Able to Re-induce a Remission if a Flare-up Occurs Day 1 to Day 57 A flare was defined as an increase of inflammation in either eye so that the anterior chamber cell score or the vitreous haze score become 1+ or greater. Vitreous haze was evaluated with an indirect ophthalmoscope and a hand-held 20-diopter lens. Haze is defined as a reduction in the clarity of fundus details seen through the vitreous, the degree of haze was quantified using standard National Eye Institute (NEI) photographs. The standard photographs provide a grading scale with photographs of fundi with vitreous haze grades "0" (zero), "trace" (which counts as 0.5+), 1+, 2+, 3+, and 4+. If the amount of vitreous haze appears to fall between two integer grades, the value would be recorded as halfway between the grades. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.
Number of Complete Responders in Cohort 2, 3 and 6 at Day 57 Day 1 (Baseline), Day 57 A "complete responder" was defined as a participant who was able to stop all topical and systemic corticosteroids in both eyes and maintain remission of uveitis (=remains a responder as defined above) lasting at least 1 week (since stopping corticosteroids, if corticosteroids were given).
Number of Participants Who Were Able to Induce a Remission in Uveitis Day 1 to Day 85 Participants with uveitis who were able to stop all topical and systemic topical corticosteroids in both eyes by Day 57 visit after the first course of one or two doses of AIN457 were to be categorized as nonresponders and were to be discontinued from the study at the Day 85 visit. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.
Number of Responders in Cohort 1, 2, 3 and 6 at Day 57 Day 1 (Baseline), Day 57 A "responder" was defined as a participant who fulfilled at least one of the 3 criteria compared to baseline: 1. Increase in visual acuity by at least 15 letters using Early Treatment Diabetic Retinopathy Study method, no increase in daily prednisone dose compared to week 1 and without worsening of uveitis. 2. Decrease in vitreous haze by 2 steps or more or for participants with anterior uveitis, resolution of the anterior chamber inflammation (i.e., no cells or only a rare cell in the anterior chamber (score 0 or trace (0.5+)), use measurement before dilation), no increase in daily prednisone dose compared to week 1 and without any worsening of uveitis.3 For those participant on a. \>20 mg/day of prednisone during week 1: Reduction in daily prednisone dose to 10 mg/day or less. b. ≤20 mg/day of prednisone during week 1: Reduction in daily prednisone dose to 0 mg/day. c. topical corticosteroids during week 1: Reduction in daily topical corticosteroid dose to 0 during the last 2 weeks.
Number of Participants With Reduction in Oral Prednisone or Topical Corticosteroid and Other Immunosuppressant Drugs Baseline (Day 1) up to Month 8 Participants intake of oral prednisone or topical corticosteroid and other immunosuppressant drugs was reduced if participant was on up to 1.5 mg/kg/day dose of prednisone during the week prior to Day 1 or whom the resumption of prednisone was not considered the appropriate systemic therapy by investigator or who have never been on systemic immunosuppressive therapy and whose uveitis was so severe that, in the clinician's judgment, prednisone at a dose of 1.0-1.5 mg/kg/day alone will be insufficient to control the uveitis or participant with HLA-B27-associated anterior uveitis who would ordinarily be started on systemic prednisone. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇩🇪Tübingen, Germany