Safety and Efficacy of AIN457 in Patients With Quiescent Non-infectious Uveitis (ENDURE)

October 8, 2015 updated by: Novartis Pharmaceuticals

A 24 Week Multi-center, Randomized, Double-masked, Placebo Controlled, Dose-ranging Phase III Study of AIN457 Versus Placebo for Maintaining Uveitis Suppression When Reducing Systemic Immunosuppression in Patients With Quiescent, Non-infectious Intermediate, Posterior or Panuveitis.

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

125

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Rio de Janeiro, Brazil, 21941-590
        • Novartis Investigative Site
      • São Paulo, Brazil, 04040-002
        • Novartis Investigative Site
      • São Paulo, Brazil, 05403-000
        • Novartis Investigative Site
    • SP
      • Sao Paulo, SP, Brazil, 05403-000
        • Novartis Investigative Site
      • São Paulo, SP, Brazil, 04023-900
        • Novartis Investigative Site
      • Berlin, Germany, 13353
        • Novartis Investigative Site
      • Chemnitz, Germany, 09113
        • Novartis Investigative Site
      • Dessau-Rosslau, Germany, 06847
        • Novartis Investigative Site
      • Dessau-Rosslau, Germany, D-06822
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Essen, Germany, 45122
        • Novartis Investigative Site
      • Freiburg, Germany, 79106
        • Novartis Investigative Site
      • Kiel, Germany, 24105
        • Novartis Investigative Site
      • Muenster, Germany, 48145
        • Novartis Investigative Site
      • Tübingen, Germany, 72076
        • Novartis Investigative Site
      • Chandigarh, India, 160 012
        • Novartis Investigative Site
      • Chennai, India, 600006
        • Novartis Investigative Site
      • Coimbatore, India, 641014
        • Novartis Investigative Site
      • Kolkatta, India, 700 073
        • Novartis Investigative Site
      • Madurai, India, 625020
        • Novartis Investigative Site
      • New Delhi, India, 110 029
        • Novartis Investigative Site
    • Karnataka
      • Bangalore, Karnataka, India, 560 010
        • Novartis Investigative Site
    • Tamil Nadu
      • Chennai, Tamil Nadu, India, 600006
        • Novartis Investigative Site
      • Madurai, Tamil Nadu, India, 625020
        • Novartis Investigative Site
    • Telangana
      • Hyderabad, Telangana, India, 500 034
        • Novartis Investigative Site
      • Jerusalem, Israel, 91120
        • Novartis Investigative Site
      • Petach Tikva, Israel, 49100
        • Novartis Investigative Site
      • Petach-Tikva, Israel, 49100
        • Novartis Investigative Site
      • Ramat Gan, Israel, 5262100
        • Novartis Investigative Site
      • Tel-Aviv, Israel, 64239
        • Novartis Investigative Site
      • Ancona, Italy, 60126
        • Novartis Investigative Site
      • Milano, Italy, 20157
        • Novartis Investigative Site
      • Milano, Italy, 20132
        • Novartis Investigative Site
      • Parma, Italy, 43100
        • Novartis Investigative Site
      • Roma, Italy, 00100
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20132
        • Novartis Investigative Site
    • PR
      • Parma, PR, Italy, 43100
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00100
        • Novartis Investigative Site
      • Baracaldo, Spain, 48903
        • Novartis Investigative Site
      • Barcelona, Spain, 08035
        • Novartis Investigative Site
      • Barcelona, Spain, 08028
        • Novartis Investigative Site
      • Madrid, Spain, 28040
        • Novartis Investigative Site
      • Santiago de Compostela, Spain, 15705
        • Novartis Investigative Site
      • Valencia, Spain, 46014
        • Novartis Investigative Site
      • Valencia, Spain, 46009
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46026
        • Novartis Investigative Site
    • Galicia
      • Santiago de Compostela, Galicia, Spain, 15705
        • Novartis Investigative Site
    • Vizcaya
      • Baracaldo, Vizcaya, Spain, 48903
        • Novartis Investigative Site
      • Bern, Switzerland, 3010
        • Novartis Investigative Site
      • Bern, Switzerland, 3012
        • Novartis Investigative Site
      • Lausanne, Switzerland, 1003
        • Novartis Investigative Site
      • Lausanne, Switzerland, 1004
        • Novartis Investigative Site
      • Luzern, Switzerland, 6000
        • Novartis Investigative Site
      • St. Gallen, Switzerland, 9007
        • Novartis Investigative Site
      • Zuerich, Switzerland, 8063
        • Novartis Investigative Site
    • CHE
      • Lausanne, CHE, Switzerland, 1004
        • Novartis Investigative Site
      • Ankara, Turkey, 06490
        • Novartis Investigative Site
      • Fatih / Istanbul, Turkey, 34098
        • Novartis Investigative Site
      • Istanbul, Turkey, 34390
        • Novartis Investigative Site
      • Birmingham, United Kingdom, B18 7QU
        • Novartis Investigative Site
      • Bristol, United Kingdom, BS1 2LX
        • Novartis Investigative Site
      • Bristol, United Kingdom, BD1 2LX
        • Novartis Investigative Site
      • Liverpool, United Kingdom, L7 8XP
        • Novartis Investigative Site
      • London, United Kingdom, SE1 7EH
        • Novartis Investigative Site
      • London, United Kingdom, EC1V 2PD
        • Novartis Investigative Site
      • York, United Kingdom, YO31 8HE
        • Novartis Investigative Site
    • California
      • Artesia, California, United States, 90701
        • Sall Research Medical Center
      • Artesia, California, United States, 90704
        • Novartis Investigative Site
      • Beverly Hills, California, United States, 90211
        • Novartis Investigative Site
      • Beverly Hills, California, United States, 90211
        • Retina-Vitreous Assoc. Medical Group
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
      • Atlanta, Georgia, United States, 30322
        • Novartis Investigative Site
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Novartis Investigative Site
      • Louisville, Kentucky, United States, 40202
        • University of Louisville Opthamology
    • Maryland
      • Baltimore, Maryland, United States, 21205-2005
        • Novartis Investigative Site
      • Baltimore, Maryland, United States, 21287
        • The Wilmer Eye Institute
    • Massachusetts
      • Cambridge, Massachusetts, United States, 02142
        • Novartis Investigative Site
      • Cambridge, Massachusetts, United States, 02142
        • Massachusets Eye Research and Surgery Institution (MERSI)
    • New Jersey
      • Teaneck, New Jersey, United States, 07666
        • Novartis Investigative Site
      • Teaneck, New Jersey, United States, 07666
        • The Cornea and Laser Institute and UMDNJ
    • North Carolina
      • Belmont, North Carolina, United States, 28012
        • Charlotte Eye, Ear, Nose, and Throat Associates
      • Charlotte, North Carolina, United States, 28210
        • Novartis Investigative Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Novartis Investigative Site
      • Portland, Oregon, United States, 97239
        • OHSU, Casey Eye Institute
    • Texas
      • Arlington, Texas, United States, 76012
        • Texas Retina Associates
      • Arlington, Texas, United States, 76012
        • Novartis Investigative Site
      • Houston, Texas, United States, 77025
        • Novartis Investigative Site
      • Houston, Texas, United States, 77025
        • Houston Eye Associates
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington
      • Seattle, Washington, United States, 98195
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with quiescent chronic, non-infectious intermediate uveitis, posterior uveitis or panuveitis as evidenced by <1+ anterior chamber cell grade and <1+ vitreous haze in both eyes for at least 6 weeks prior to screening.
  • Requirement for either of the following immunosuppressive therapies at any time within the past 3 months for the treatment or prevention of uveitis which must not have been increased within the 6 weeks prior to screening:

Prednisone or equivalent ≥10 mg daily.

≥1 periocular injection or ≥1 intravitreal corticosteroid injection (i.e. 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 as monotherapy or in combination with or without steroids. (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.

Exclusion Criteria:

Ocular concomitant conditions/disease

  • 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 active, non-infectious intermediate, posterior or panuveitis in one or both eyes (≥1+ anterior chamber cells and /or ≥1+ vitreous haze.)
  • Patients receiving or that may require corticosteroids (prednisone or equivalent) ≥1 mg/kg/day to maintain quiescence of their intraocular inflammation.

Ocular treatments

  • Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening.
  • Treatment with fluocinolone acetonide implant (Retisert®) 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.

Systemic conditions or treatments

  • 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/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AIN457 300mg s.c weekly for 3 weeks
AIN457 300mg s.c weekly for 3 weeks then every 2 weeks
AIN457 300mg s.c weekly for 3 weeks then every 2 weeks
AIN457 300mg s.c at baseline and Week 2 then every 4 weeks
AIN457 150mg s.c at baseline and Week 2 then every 4 weeks
Experimental: AIN457 300mg s.c at baseline and Week 2
AIN457 300mg s.c at baseline and Week 2 then every 4 weeks
AIN457 300mg s.c weekly for 3 weeks then every 2 weeks
AIN457 300mg s.c at baseline and Week 2 then every 4 weeks
AIN457 150mg s.c at baseline and Week 2 then every 4 weeks
Experimental: AIN457 150mg s.c at baseline and Week 2
AIN457 150mg s.c at baseline and Week 2 then every 4 weeks
AIN457 300mg s.c weekly for 3 weeks then every 2 weeks
AIN457 300mg s.c at baseline and Week 2 then every 4 weeks
AIN457 150mg s.c at baseline and Week 2 then every 4 weeks
Placebo Comparator: Placebo s.c weekly for 3 weeks
Placebo s.c weekly for 3 weeks then every 2 weeks
Placebo s.c weekly for 3 weeks then every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline
Time Frame: Baseline to 24 weeks
Kaplan-Meier estimates for the time to the first recurrence in any eye of active intermediate, posterior, or panuveitis from baselineRecurrence of active intermediate, posterior, or panuveitis 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 of ≥ 10 ETDRS letters
Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From Baseline to 24 Weeks
Time Frame: Baseline to 24 weeks
Participants could have received up to 5 immunosuppresive agents (prednisone, cyclosporine, azathioprine, methotrexate, mycophenolate). Immunosuppressive Medication Score (IMS) is a combined, single numeric score derived on basis of total daily dose of specific immunosuppressive agents / unit body weight, ranged on a scale from 0-9 for the total daily dose in mg per kg. Patients receiving multiple medications, the sum of the grading scores for each drug was used to calculate a total immunosuppression score at each visit. 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 (or its reduction from baseline) showed better clinical outcome
Baseline to 24 weeks
Mean Change in Best Corrected Visual Acuity From Baseline
Time Frame: Baseline to 24 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.
Baseline to 24 weeks
Mean Change in Vitreous Haze Grade From Baseline to 24 Weeks
Time Frame: Baseline to 24 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
Baseline to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2010

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

December 14, 2009

First Submitted That Met QC Criteria

December 15, 2009

First Posted (Estimate)

December 16, 2009

Study Record Updates

Last Update Posted (Estimate)

November 5, 2015

Last Update Submitted That Met QC Criteria

October 8, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Other Study ID Numbers

  • CAIN457C2301
  • 2009-014835-19 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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