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Safety and Efficacy of AIN457 in Noninfectious Uveitis

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ClinicalTrials.gov Identifier: NCT00685399
Recruitment Status : Completed
First Posted : May 28, 2008
Results First Posted : July 17, 2017
Last Update Posted : July 17, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 23, 2008
First Posted Date  ICMJE May 28, 2008
Results First Submitted Date  ICMJE February 12, 2015
Results First Posted Date  ICMJE July 17, 2017
Last Update Posted Date July 17, 2017
Study Start Date  ICMJE June 2008
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2017)
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 27, 2008)
To assess the safety and tolerability of intravenous AIN457A in the treatment of non-infectious uveitis
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2017)
  • Number of Responders in Cohort 1, 2, 3 and 6 at Day 57 [ Time Frame: 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 Complete Responders in Cohort 2, 3 and 6 at Day 57 [ Time Frame: 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 With Reduction in Oral Prednisone or Topical Corticosteroid and Other Immunosuppressant Drugs [ Time Frame: 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.
  • Number of Participants Who Were Able to Induce a Remission in Uveitis [ Time Frame: 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 Participants With Remission in Uveitis [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2008)
  • To investigate how many uveitis patients will have a reduction in uveitis in response to AIN457
  • To investigate how many patients will be able to reduce their use of corticosteroids
  • To assess the pharmacokinetics of intravenous AIN457 in patients with uveitis
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of AIN457 in Noninfectious Uveitis
Official Title  ICMJE An Open-label Proof-of-concept Study With a Double-masked, Dose-ranging Component to Assess the Effects of AIN457 in Patients With Noninfectious Uveitis
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Non-infectious Uveitis
Intervention  ICMJE
  • Drug: AIN457
    AIN457 subcutaneous dose
    Other Name: Secukinumab
  • Drug: AIN 457
    AIN457 low dose (i.v)
    Other Name: Secukinumab
  • Drug: AIN457
    AIN457 high dose (i.v)
    Other Name: Secukinumab
Study Arms  ICMJE
  • Experimental: Cohort 1
    Participants were administered with AIN457 (Sp2/0derived) 10 milligrams per kilogram (mg/kg) intravenous (i.v.) dose on Day 1 and Day 22.
    Intervention: Drug: AIN457
  • Experimental: Cohort 2
    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.
    Intervention: Drug: AIN457
  • Experimental: Cohort 3
    Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.
    Intervention: Drug: AIN 457
  • Experimental: Cohort 4
    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.
    Intervention: Drug: AIN 457
  • Experimental: Cohort 5
    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.
    Intervention: Drug: AIN457
  • Experimental: Cohort 6 Arm 1
    Participants were administered with AIN457 300 mg subcutaneously (s.c.) and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43).
    Intervention: Drug: AIN457
  • Experimental: Cohort 6 Arm 2
    Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43).
    Intervention: Drug: AIN 457
  • Experimental: Cohort 6 Arm 3
    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.
    Intervention: Drug: AIN457
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 15, 2017)
76
Original Estimated Enrollment  ICMJE
 (submitted: May 27, 2008)
15
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Active uveitis (i.e., uveitis that is not in remission).
  • Intermediate uveitis, posterior uveitis, or panuveitis must be sufficiently severe that systemic immunosuppression is indicated.

Exclusion criteria:

  • Active infection.
  • Weight must not be greater that 120kg.

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00685399
Other Study ID Numbers  ICMJE CAIN457A2208
2011-001243-67 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP