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

This study has been terminated.
(Results of a planned interim analysis did not show significant effects for any of the 3 AIN dose regimens versus placebo on any primary or secondary endpoint)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01032915
First received: December 14, 2009
Last updated: October 8, 2015
Last verified: October 2015
  Purpose
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.

Condition Intervention Phase
Non-infectious Uveitis
Biological: AIN457
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Time to First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From Baseline to 24 Weeks [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    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

  • Mean Change in Best Corrected Visual Acuity From Baseline [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    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.

  • Mean Change in Vitreous Haze Grade From Baseline to 24 Weeks [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    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


Enrollment: 125
Study Start Date: February 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AIN457 300mg s.c weekly for 3 weeks
AIN457 300mg s.c weekly for 3 weeks then every 2 weeks
Biological: AIN457
AIN457 300mg s.c weekly for 3 weeks then every 2 weeks
Experimental: AIN457 300mg s.c at baseline and Week 2
AIN457 300mg s.c at baseline and Week 2 then every 4 weeks
Biological: AIN457
AIN457 300mg 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
Biological: AIN457
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
Drug: Placebo
Placebo s.c weekly for 3 weeks then every 2 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  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: NCT01032915

  Show 92 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01032915     History of Changes
Other Study ID Numbers: CAIN457C2301  2009-014835-19 
Study First Received: December 14, 2009
Results First Received: February 12, 2015
Last Updated: October 8, 2015
Health Authority: United States: Food and Drug Administration
Switzerland: Swissmedic
Germany: Paul-Ehrlich-Institut
Spain: Spanish Agency of Medicines
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Brazil: National Health Surveillance Agency
India: Ministry of Health
Israel: Ministry of Health

Keywords provided by Novartis:
Quiescent uveitis
intermediate uveitis
panuveitis
posterior uveitis
uveitis

Additional relevant MeSH terms:
Uveitis
Uveal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on July 28, 2016