Phase III Study in Refractory Behcet's Disease (SHIELD)

Novartis

Status and phase: Completed; Phase 3

Conditions: Behcet Disease

Treatments: Drug: Placebo; Drug: AIN457

Study type: Interventional

Funder types: Industry

Identifiers

NCT00995709

CAIN457C2303

2009-011237-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 118 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Ocular treatments

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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118 participants in 3 patient groups, including a placebo group

AIN457C 300 mg every 2 week dosage regimen

Experimental group

Description:

AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg each. every 2 weeks

Treatment:

Drug: AIN457

Drug: AIN457

AIN457C 300 mg monthly dosage regimen

Experimental group

Description:

AIN457 300 mg was administered in 2 subcutaneous (s.c.) injections of 150 mg e

Treatment:

Drug: AIN457

Drug: AIN457

Placebo

Placebo Comparator group

Description:

Placebo was administered in 2 s.c. injections every 2 weeks

Treatment:

Drug: Placebo