This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Safety and Efficacy of AIN457 in Noninfectious Uveitis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00685399
First received: May 23, 2008
Last updated: June 15, 2017
Last verified: June 2017
  Purpose
This study was performed to evaluate the efficacy and safety of AIN457 for patients with active uveitis that requires systemic immunosuppression.

Condition Intervention Phase
Non-infectious Uveitis Drug: AIN457 Drug: AIN 457 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 76
Study Start Date: June 2008
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: AIN457
AIN457 subcutaneous dose
Other Name: Secukinumab
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.
Drug: AIN457
AIN457 subcutaneous dose
Other Name: Secukinumab
Experimental: Cohort 3
Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.
Drug: AIN 457
AIN457 low dose (i.v)
Other Name: Secukinumab
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.
Drug: AIN 457
AIN457 low dose (i.v)
Other Name: Secukinumab
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.
Drug: AIN457
AIN457 high dose (i.v)
Other Name: Secukinumab
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).
Drug: AIN457
AIN457 high dose (i.v)
Other Name: Secukinumab
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).
Drug: AIN 457
AIN457 low dose (i.v)
Other Name: Secukinumab
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.
Drug: AIN457
AIN457 high dose (i.v)
Other Name: Secukinumab

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00685399

Locations
United States, California
Novartis Investigative Site
Beverly Hills, California, United States, 90211
Novartis Investigative Site
Los Angeles, California, United States, 90033
Novartis Investigative Site
Sacramento, California, United States, 95819
United States, Colorado
Novartis Investigative Site
Denver, Colorado, United States, 80210
Novartis Investigative Site
Golden, Colorado, United States, 80401
Novartis Investigative Site
Littleton, Colorado, United States, 80120
United States, Georgia
Novartis Investigative Site
Atlanta, Georgia, United States, 30322
United States, Maryland
Novartis Investigative Site
Baltimore, Maryland, United States, 21201
Novartis Investigative Site
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Novartis Investigative Site
Cambridge, Massachusetts, United States, 02142
United States, Missouri
Novartis Investigative Site
Kansas City, Missouri, United States, 64111
United States, New Jersey
Novartis Investigative Site
Teaneck, New Jersey, United States, 07666
United States, New York
Novartis Investigative Site
New York, New York, United States, 10022
Novartis Investigative Site
Slingerlands, New York, United States, 12159
United States, North Carolina
Novartis Investigative Site
Durham, North Carolina, United States, 27710
United States, Ohio
Novartis Investigative Site
Cleveland, Ohio, United States, 44195
United States, South Carolina
Novartis Investigative Site
Spartanburg, South Carolina, United States, 29306
United States, Texas
Novartis Investigative Site
Arlington, Texas, United States, 76012
Novartis Investigative Site
Austin, Texas, United States, 78793
Novartis Investigative Site
Houston, Texas, United States, 77030
Germany
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Heidelberg, Germany, 691120
Novartis Investigative Site
Tübingen, Germany, 72076
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00685399     History of Changes
Other Study ID Numbers: CAIN457A2208
2011-001243-67 ( EudraCT Number )
Study First Received: May 23, 2008
Results First Received: February 12, 2015
Last Updated: June 15, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Uveitis
eye
IL-17
IL-17A
IL17
AIN457
Vogt-Koyanagi-Harada
Behcet's
Behcet
Sympathetic ophthalmia
Multifocal choroiditis
Birdshot
HLA-B27
Birdshot retinochoroiditis
Retinal vasculitis
Sarcoidosis
Intermediate uveitis
Panuveitis
Posterior uveitis

Additional relevant MeSH terms:
Uveitis
Uveal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on September 19, 2017