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

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)

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

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • Novartis Investigative Site
    • North York, Ontario, Canada, M3N 2V6
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Novartis Investigative Site
• Egypt
  • Cairo, Egypt
    • Novartis Investigative Site
• France
  • Nantes, France, 44093
    • Novartis Investigative Site
• Germany
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Göttingen, Germany, D-37075
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1083
    • Novartis Investigative Site
• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380004
      • Novartis Investigative Site
• Israel
  • Afula, Israel, 18101
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Tel-Aviv, Israel, 64239
    • Novartis Investigative Site
• Japan
  • Kyoto, Japan, 602-8566
    • Novartis Investigative Site
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
  • Fukushima
    • Fukushima-city, Fukushima, Japan, 960-1295
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo-city, Hokkaido, Japan, 060-8648
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 545-8586
      • Novartis Investigative Site
    • Suita-city, Osaka, Japan, 565-0871
      • Novartis Investigative Site
  • Tochigi
    • Shimotsuka-gun, Tochigi, Japan, 321-0293
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • Novartis Investigative Site
    • Mitaka-city, Tokyo, Japan, 181-8611
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 308433
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Bern, Switzerland, 3012
    • Novartis Investigative Site
  • Luzern, Switzerland, 6000
    • Novartis Investigative Site
  • St. Gallen, Switzerland, 9007
    • Novartis Investigative Site
  • CHE
    • Lausanne, CHE, Switzerland, 1004
      • Novartis Investigative Site
• United Kingdom
  • York, United Kingdom, YO31 8HE
    • Novartis Investigative Site
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Novartis Investigative Site
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02142
      • Novartis Investigative Site
  • New York
    • Slingerlands, New York, United States, 12159
      • 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:

• 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 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 s.c every 2 weeks; AIN457 300 mg s.c. at baseline, Week 1 and Week 2, then every 2 weeks.	Drug: AIN457
Experimental: AIN457 300mg s.c. every 4 weeks; AIN457 300 mg s.c. at baseline and Week 2, then every 4 weeks.	Drug: AIN457
Experimental: AIN457 150mg s.c every 4 weeks; AIN457 150 mg s.c. at baseline and Week 2, then every 4 weeks	Drug: AIN457
Placebo Comparator: Placebo s.c every 2 weeks; Placebo s.c at baseline, Week 1 and Week 2, then every 2 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Dick AD, Tugal-Tutkun I, Foster S, Zierhut M, Melissa Liew SH, Bezlyak V, Androudi S. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology. 2013 Apr;120(4):777-87. doi: 10.1016/j.ophtha.2012.09.040. Epub 2013 Jan 3.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: March 25, 2010
• First Submitted That Met QC Criteria: March 26, 2010
• First Posted (Estimate): March 30, 2010

Study Record Updates

• Last Update Posted (Estimate): November 3, 2015
• Last Update Submitted That Met QC Criteria: October 5, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: uveitis; intermediate uveitis; panuveitis; posterior uveitis; Active uveitis
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Uveitis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457C2302; 2009-014834-22