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

Uveitis Clinical Trial

— INSURE  

Official title:

A 28-week Multicenter, Randomized, Double-masked, Placebo Controlled, Dose-ranging Phase III Study to Assess AIN457 Versus Placebo in Inducing and Maintaining Uveitis Suppression in Adults With Active, Non-infectious, Intermediate, Posterior or Panuveitis Requiring Immunosuppression (INSURE Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01095250
• Other study ID #: CAIN457C2302
• Secondary ID: 2009-014834-22
• Status: Terminated
• Phase: Phase 3
• First received: March 25, 2010
• Last updated: October 5, 2015
• Start date: April 2010
• Est. completion date: October 2010

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Greece: National Organization of MedicinesHungary: National Institute of PharmacyCanada: Health CanadaEgypt: Ministry of Health and PopulationJapan: Ministry of Health, Labor and WelfareSingapore: Department of Health 3/F, Public Health Laboratory CentreSwitzerland: SwissmedicGermany: Paul-Ehrlich-InstitutSpain: Spanish Agency of MedicinesItaly: Comitato Etico per la Sperimentazione Clinica dei Medicinali Dell'Azienda Ospedaliero -Universitaria Careggi di FirenzeTurkey: IEGM (The General Directorate of Pharmaceuticals and Pharmacy)United Kingdom: Medicines and Healthcare Products Regulatory 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: 30
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female subjects =18 years of age. Where relevant, parents will also sign the informed consent according to local laws and regulations

• Patients with diagnosis of chronic non-infectious intermediate uveitis, posterior uveitis or panuveitis in at least one eye

• Evidence of active intermediate, posterior or panuveitis (grade = 2+ vitreous haze with or without the presence of anterior chamber cells) at screening and baseline in at least one eye

• Requirement for any of the following immunosuppressive therapies for the treatment or prevention of uveitis:

• Prednisone or equivalent =10 mg daily at any time within the past 3 months.

• =1 periocular injection or =1 intravitreal corticosteroid injection (e.g. 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 at any time within the past 3 months (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.

• Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed

Exclusion Criteria:

Ocular concomitant conditions/disease

• Patients receiving or that may require prednisone (or equivalent) =1.5 mg/kg/day for the treatment of their active uveitis

• 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 infectious uveitis or uveitis of an underlying diagnosis that is uncertain and would reasonably include a disease for which immunosuppression would be contraindicated (e.g. ocular lymphoma)

Ocular treatments

• Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening

• Treatment with fluocinolone acetonide implant 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

• Ocular disease that would interfere with ocular evaluations (e.g. corneal scarring, cataract, vitreous hemorrhage) or that in the opinion of the investigator would complicate the evaluation of the safety or efficacy of the study treatment (e.g. uncontrolled glaucoma, toxoplasma scar, macular scarring)

• Current use of or likely need for systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine, ethambutol, etc.)

Systemic conditions or treatments

• Any previous treatment with AIN457

• 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, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Uveitis

Intervention

Drug:
• AIN457

• AIN457

• AIN457

• Placebo

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	North York	Ontario
Egypt	Novartis Investigative Site	Cairo
France	Novartis Investigative Site	Nantes
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Göttingen
Hungary	Novartis Investigative Site	Budapest
India	Novartis Investigative Site	Ahmedabad	Gujarat
Israel	Novartis Investigative Site	Afula
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel-Aviv
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Fukushima-city	Fukushima
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Mitaka-city	Tokyo
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Shimotsuka-gun	Tochigi
Japan	Novartis Investigative Site	Suita-city	Osaka
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne	CHE
Switzerland	Novartis Investigative Site	Luzern
Switzerland	Novartis Investigative Site	St. Gallen
United Kingdom	Novartis Investigative Site	York
United States	Novartis Investigative Site	Arlington	Texas
United States	Novartis Investigative Site	Beverly Hills	California
United States	Novartis Investigative Site	Cambridge	Massachusetts
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Slingerlands	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Egypt,  France,  Germany,  Hungary,  India,  Israel,  Japan,  Singapore,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Vitreous Haze Grade in the Study Eye From Baseline to 28 Weeks or at Time of Rescue, if Earlier.	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.	baseline to 28 weeks	No
Secondary	Proportion of Responders With no Recurrence of Active Intermediate, Posterior, or Panuveitis in the Study Eye at 28 Weeks	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.	baseline to 28 weeks	No
Secondary	Mean Change in Best Corrected Visual Acuity From Baseline to 28 Weeks	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.	baseline to 28 weeks	No
Secondary	Change From Baseline in Quality of Life/Patient Reported Outcome Assessments	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.	baseline to 28 weeks	No
Secondary	Mean Change in Vitreous Haze Grade and Anterior Chamber Cell Grade From Baseline to 28 Weeks	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.	baseline to 28 weeks	No
Secondary	Change in Immunosuppressive Medication Score From Baseline to Week 28	No patients of Study CAIN457C2303 achieved the milestone of the primary endpoint in non-infectious uveitis patients with Behçet's disease. Study CAIN457C2302 (active uveitis study) was terminated to avoid continuing patients on a study with a low probability of success.Since patients did not reach the endpoint of analysis there can be no meaningful interpretation of data and data will be not provided.	baseline to 28 weeks	No