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

A 38-week Extension to a 24-week Multicenter, 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 extension study will assess the safety and efficacy of AIN457 versus placebo for maintaining uveitis suppression when reducing systemic immunosuppression

Study Overview

• Status: Terminated
• Conditions: Non-infectious Uveitis
• Intervention / Treatment: Drug: AIN457; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Novartis Investigative Site
    • São Paulo, SP, Brazil, 04023-900
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
• India
  • New Delhi, India, 110 029
    • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5266202
    • Novartis Investigative Site
  • Tel-Aviv, Israel, 6423906
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15705
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Bern, Switzerland, 3012
    • Novartis Investigative Site
  • Lausanne, Switzerland, 1003
    • 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
• United Kingdom
  • Birmingham, United Kingdom, B18 7QU
    • Novartis Investigative Site
  • Liverpool, United Kingdom, L7 8XP
    • Novartis Investigative Site
  • London, United Kingdom, SE1 7EH
    • Novartis Investigative Site
  • York, United Kingdom, YO31 8HE
    • Novartis Investigative Site
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Novartis Investigative Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21205-2005
      • Novartis Investigative Site
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02142
      • Novartis Investigative Site
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Novartis Investigative Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Novartis Investigative Site
    • Houston, Texas, United States, 77025
      • Novartis Investigative Site

Participation Criteria

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 who have completed the entire treatment period of the 24 week core study

Exclusion Criteria:

• Inability or unwillingness to undergo repeated subcutaneous injections; inability to comply with study or follow-up procedures; any medical or psychiatric condition which, in the investigator's opinion wouldpreclude the participant from adhering to the protocol or completing the study per protocol.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AIN457 300mg every 2 weeks; AIN457 300 mg subcutaneous (s.c.) weekly for 3 weeks followed by AIN457 300 mg s.c. every 2 weeks	Drug: AIN457; AIN457 150 mg powder for solution was provided in glass vials each containing 150 mg AIN457 as a lyophilized cake
Experimental: AIN457 300 mg every 4 weeks; AIN457 300 mg s.c. at baseline for Week 2 followed by AIN457 300 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly	Drug: AIN457; AIN457 150 mg powder for solution was provided in glass vials each containing 150 mg AIN457 as a lyophilized cake
Experimental: AIN457 150 mg every 4 weeks; AIN457 150 mg s.c. and placebo s.c. at Baseline and Week 2 followed by AIN457 150 mg s.c. monthly, alternating with placebo s.c. at Weeks 1 and 4 and then monthly	Drug: AIN457; AIN457 150 mg powder for solution was provided in glass vials each containing 150 mg AIN457 as a lyophilized cake
Placebo Comparator: Placebo; Placebo s.c. every 2 weeks	Drug: Placebo; Matching placebo to AIN457

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Time to the First Recurrence in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline	Kaplan-Meier estimates for the time to the first recurrence in any eye of active intermediate, posterior, or panuveitis from baseline 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, core and extension	Baseline to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Vitreous Haze Score for the Study Eye From Baseline to the Highest Post-baseline Value	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 52 weeks
Mean Change in Best Corrected Visual Acuity From Baseline, Core and Extension	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 52 weeks
Number of Participants With First Recurrence in in Any Eye of Active Intermediate, Posterior, or Panuveitis From Baseline During the Core and Extension Studies	Evaluation of recurrence until resolution is ascertained, based on the first criteria (a >2 step increase in vitreous haze with or without an increase in anterior chamber cell grade in either eye). A 2 step increase is defined as any of the following changes: 0-2, 0.5-2, 1-3, 2-4	Baseline to 52 weeks
Composite Immunosuppressive Medication Score From Baseline to Week 52, Core and Extension	IMS is a combined, single numeric score derived on the basis of the total daily dose of specific immunosuppressive agents per unit body weight, ranged on a scale from 0 to 9 for the total daily dose in milligrams per kilogram. The total IMS is the sum of the scores derived for the agents included into the score. The treatment groups will be compared using an analysis of covariance with treatment, region, and baseline IMS as covariate. 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 showed better clinical outcome.	Baseline to 52 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: March 18, 2010
• First Submitted That Met QC Criteria: March 18, 2010
• First Posted (Estimate): March 19, 2010

Study Record Updates

• Last Update Posted (Estimate): January 14, 2016
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: uveitis; intermediate uveitis; panuveitis; posterior uveitis; Quiescent uveitis; NVS Definition: Words or phrases that best describe the protocol. Keywords help users find studies in the database.; Avoid acronyms, abbreviations and trade names.; Examples: Heart failure, aliskiren, heart attack, cardiovascular diseases; Psoriasis, inflammatory skin disease, scaly patches
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Uveitis
• Other Study ID Numbers: CAIN457C2301E1; 2009-015508-24