Phase III Study in Refractory Behcet's Disease (SHIELD)
This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
First received: October 13, 2009
Last updated: November 6, 2014
Last verified: October 2014
The purpose of this pivotal trial is to evaluate subcutaneous (SQ) AIN457 as an adjunctive therapy to reduce the rate of exacerbations of posterior uveitis or panuveitis secondary to Behçet's disease during the 24 weeks of study therapy as compared to standard of care alone.
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
||A 24 Week Multicenter, Randomized, Double-masked, Placebo Controlled Study to Assess the Difference in the Rate of Recurrent Exacerbations in Behçets Patients With Posterior or Panuveitis Treated With AIN457 vs Placebo Adjunctive to Standard-of-care Immunosuppressive Therapy
Primary Outcome Measures:
- To determine if AIN457 is effective in reducing the rate of posterior segment uveitis exacerbations secondary to Behçet's disease, as assessed by visual acuity, anterior chamber cells and vitreous haze. [ Time Frame: Wk 1-8; wk 12; wk 16; wk 22, and wk 24 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To determine if AIN457 can reduce the need for standard-of-care immunosuppressive medications (ISM) in patients requiring systemic immunosuppression to treat/prevent posterior segment uveitis secondary to Behçet's disease as measured by the ISM score. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- To assess the safety of targeted IL-17 inhibition with AIN457 in patients with posterior segment uveitis secondary to Behçet's disease receiving standard-of-care immunomodulatory therapy as measured by applanation tonometry and adverse events. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
- To determine the effect of AIN457 on macular edema and visual acuity in patients with posterior segment uveitis secondary to Behçet's disease as determined by optical coherence tomography. [ Time Frame: screening, baseline, and wk 24 (end of study) ] [ Designated as safety issue: No ]
- To establish the impact of AIN457 on quality of life of posterior segment uveitis patients secondary to Behçet's disease refractory to systemic immunomodulatory therapy as measured by National Eye Institute Visual Function Questionaire-25 and Euroqol. [ Time Frame: screening, and wk 24 (end of study) ] [ Designated as safety issue: No ]
- To observe the effect of AIN457 on the systemic non-ocular manifestations of Behçet's disease in patients with posterior segment uveitis requiring systemic immunosuppression as measured by the Bechet's disease current activity form. [ Time Frame: baseline and wk 24 (end of study) ] [ Designated as safety issue: No ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||July 2010 (Final data collection date for primary outcome measure)
Experimental: AIN457C every 2 weeks
300 mg every 2 week dosage regimen
300 mg every 2 weeks
Experimental: AIN457C monthly
300 mg monthly dosage regimen
300 mg monthly
Placebo Comparator: Placebo
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Patients with Behçet's disease and with a history of recurrent uveitis in a least one eye.
Documented evidence of >2 recurrent exacerbations of either intermediate uveitis, posterior uveitis or panuveitis in the study eye within the past 6 months (this could include the current exacerbation for patients having an acute exacerbation at screening). Exacerbations fulfilling the study inclusion criteria must have one or more of the following recorded in the patients patients medical record for each recurrent exacerbation:
- >2+ vitreous haze with <2+ anterior chamber cell grade (intermediate or posterior uveitis) or >2+ vitreous haze with >2+ anterior chamber cell grade (panuveitis)
- presence of retinal infiltrates or vasculitis or hemorrhages
- documented >10 ETDRS letter or 2 line Snellen decrease in visual acuity attributed to ocular inflammation secondary to the recurrent exacerbation of Behçet's disease.
Requirement for either of the following immunosuppressive therapies for at least 3 of the past 6 months for the treatment of or to prevent an exacerbation of ocular inflammation related to Behçet's disease:
- Prednisone or equivalent >10 mg daily
- The need for at least >1 periocular injection or >1 intravitreal corticosteroid injection in the study eye within the past 6 months (the last injection must have not been given within 6 weeks of screening)
- Treatment with cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid or methotrexate either as monotherapy or in combination with or without steroids. (Patients treated at any time with chlorambucil or cyclophosphamide are not eligible for the study.)
- Patients not meeting the above specified criteria for immunomodulatory therapies are eligible for enrollment if they are intolerant to systemic immunomodulatory therapy as determined by the study investigator.
- Subjects with infectious uveitis, uveitis due to other causes than Behçet's disease, or uveitis of unknown etiology.
- Less severe (i.e. anterior) uveitis associated with Behçet's disease.
- Treatment with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to study screening.
- Treatment with any injected or implantable corticosteroid releasing device (i.e., flucinolone acetonide implant, Retisert®) in the study eye within the last 3 years.
- 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
- Treatment with any live or live-attenuated vaccine (including vaccine for varicella-zoster virus or measles) within 2 months prior to screening.
- Any systemic biologic therapy (e.g. interferon, infliximab, daclizumab, etanercept, or adalimumab) given intravenously or subcutaneously within 3 months prior to screening and no prior treatment with AIN457.
- Any prior treatment with systemic alkylating agents (cyclophosphamide, chlorambucil).
Other protocol-defined inclusion/exclusion criteria may apply
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00995709
No publications provided by Novartis
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
||Novartis ( Novartis Pharmaceuticals )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 13, 2009
||November 6, 2014
||United States: Food and Drug Administration
Keywords provided by Novartis:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 30, 2015
Skin Diseases, Vascular