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

Non-infectious Uveitis Clinical Trial

— ENDURE  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01032915
• Other study ID #: CAIN457C2301
• Secondary ID: 2009-014835-19
• Status: Terminated
• Phase: Phase 3
• First received: December 14, 2009
• Last updated: October 8, 2015
• Start date: February 2010
• Est. completion date: June 2011

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSwitzerland: SwissmedicGermany: Paul-Ehrlich-InstitutSpain: Spanish Agency of MedicinesItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyBrazil: National Health Surveillance AgencyIndia: Ministry of HealthIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 125
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Non-infectious Uveitis
• Uveitis

Intervention

Biological:
• AIN457
AIN457 300mg s.c weekly for 3 weeks then every 2 weeks
• AIN457
AIN457 300mg s.c at baseline and Week 2 then every 4 weeks
• AIN457
AIN457 150mg s.c at baseline and Week 2 then every 4 weeks

Drug:
• Placebo
Placebo s.c weekly for 3 weeks then every 2 weeks

Locations

Country	Name	City	State
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Brazil	Novartis Investigative Site	São Paulo
Brazil	Novartis Investigative Site	São Paulo
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Dessau-Rosslau
Germany	Novartis Investigative Site	Dessau-Rosslau
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Tübingen
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Chandigarh
India	Novartis Investigative Site	Chennai
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative SIte	Coimbatore
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Kolkatta
India	Novartis Investigative Site	Madurai
India	Novartis Investigative Site	Madurai	Tamil Nadu
India	Novartis Investigative Site	New Delhi
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Petach-Tikva
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel-Aviv
Italy	Novartis Investigative Site	Ancona
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Parma
Italy	Novartis Investigative Site	Roma
Italy	Novartis Investigative Site	Roma	RM
Spain	Novartis Investigative Site	Baracaldo	Vizcaya
Spain	Novartis Investigative Site	Baracaldo
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Santiago de Compostela
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Lausanne	CHE
Switzerland	Novartis Investigative Site	Luzern
Switzerland	Novartis Investigative Site	St. Gallen
Switzerland	Novartis Investigative Site	Zuerich
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Fatih / Istanbul
Turkey	Novartis Investigative Site	Istanbul
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	York
United States	Novartis Investigative Site	Arlington	Texas
United States	Texas Retina Associates	Arlington	Texas
United States	Novartis Investigative Site	Artesia	California
United States	Sall Research Medical Center	Artesia	California
United States	Emory University	Atlanta	Georgia
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Baltimore	Maryland
United States	The Wilmer Eye Institute	Baltimore	Maryland
United States	Charlotte Eye, Ear, Nose, and Throat Associates	Belmont	North Carolina
United States	Novartis Investigative Site	Beverly Hills	California
United States	Retina-Vitreous Assoc. Medical Group	Beverly Hills	California
United States	Massachusets Eye Research and Surgery Institution (MERSI)	Cambridge	Massachusetts
United States	Novartis Investigative Site	Cambridge	Massachusetts
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Houston Eye Associates	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Louisville	Kentucky
United States	University of Louisville Opthamology	Louisville	Kentucky
United States	Novartis Investigative Site	Portland	Oregon
United States	OHSU, Casey Eye Institute	Portland	Oregon
United States	Novartis Investigative Site	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	Novartis Investigative Site	Teaneck	New Jersey
United States	The Cornea and Laser Institute and UMDNJ	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  Germany,  India,  Israel,  Italy,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to 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 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	No
Secondary	Change (Reduction) From Baseline in Composite Immunosuppressive Medication Score (IMS) From 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	No
Secondary	Mean Change in Best Corrected Visual Acuity From Baseline	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	No
Secondary	Mean Change in Vitreous Haze Grade From 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	No

External Links

•   Secukinumab in the Treatment of Noninfectious Uveitis: Results of Three Randomized, Controlled Clinical Trials