A 24 week multicenter, randomized, double-masked, placebo controlled study to assess the difference in the rate of recurrent exacerbations in Behçet’s patients with posterior or panuveitis treated with AIN457 vs placebo adjunctive to standard-of-care immunosuppressive therapy - C2303

• Register: EUCTR
• Last refreshed on: 2 March 2015
• Main ID: EUCTR2009-011237-27-HU
• Date of registration: 29/07/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services Ag
• Public title: A 24 week multicenter, randomized, double-masked, placebo controlled study to assess the difference in the rate of recurrent exacerbations in Behçet’s patients with posterior or panuveitis treated with AIN457 vs placebo adjunctive to standard-of-care immunosuppressive therapy - C2303
• Scientific title: A 24 week multicenter, randomized, double-masked, placebo controlled study to assess the difference in the rate of recurrent exacerbations in Behçet’s patients with posterior or panuveitis treated with AIN457 vs placebo adjunctive to standard-of-care immunosuppressive therapy - C2303
• Date of first enrolment: 15/10/2009
• Target sample size: 112
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011237-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, France, Germany, Greece, Hungary, Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male and female subjects >18 years of age
2.Patients with Behçet’s disease and with a history of recurrent uveitis in a least one eye. Patients with both active (experiencing an acute exacerbation) and quiescent (in between exacerbations) posterior uveitis or panuveitis secondary to Behçet’s disease at the time of screening are eligible for the study. The diagnosis of Behçet’s disease lies in the judgment of the investigator.
3.Documented evidence of >2 recurrent exacerbations of either 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 enrollment). Exacerbations fulfilling the study inclusion criteria must have one or more of the following recorded in the patients medical record for each recurrent exacerbation:
?>2+ vitreous haze score with <2+ anterior chamber cell grade (posterior uveitis) or >2+ vitreous haze score 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.
4.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 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 immunosuppressive therapies are eligible for the study if they are intolerant to systemic immunosuppressive therapy as determined by the study investigator
5.Patient must be able to understand and communicate with the investigator and comply with the requirements for the study and must give a written, signed, and dated informed consent before any study assessment is performed.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Ocular concomitant conditions/disease
Subjects with infectious uveitis, uveitis due to other causes than Behçet’s disease, or uveitis of unknown etiology.
Less severe (i.e. anterior or intermediate) uveitis associated with Behçet’s disease
-Ocular treatments, for instance
with intravitreal anti-VEGF agents administered to the study eye within 3 months prior to screening.
with any injected or implantable corticosteroid releasing device (i.e. fluocinolone 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 except for a diagnostic vitreous or aqueous tap with a small-gauge needle.
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)
-Systemic conditions or treatments, for instance
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.
Any prior treatment with systemic alkylating agents (cyclophosphamide, chlorambucil).
Active systemic infections during the last two weeks (exception: common cold).
Underlying metabolic, hematologic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at an unacceptable risk for participation in an immunomodulatory therapy.
Any medical or psychiatric condition which, in the investigator’s opinion would preclude the participant from adhering to the protocol or completing the study per protocol.
-Compliance/Administrative, for instance
Inability or unwillingness to undergo repeated subcutaneous injections
Inability or unwillingness to receive treatment with oral corticosteroids if recommended by the study investigator.
Participation in any other clinical investigation within 4 weeks prior to screening (or longer if required by local regulations), and for any other limitation of participation based on local regulations.
Pregnant or nursing ( lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum pregnancy test (hCG>5mIU/ml)
Women of childbearing potential (WoCBP), defined as all women physiologically capable of becoming pregnant, UNLESS they are:
? Using simultaneously double barrier or two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc., hormone replacement as either oral or implantable is acceptable as one form), from the time of screening and for the duration of the study, through study completion. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
? They are postmenopausal and had no regular menstrual bleeding for at least two (2) years prior to initial dosing. Menopause must be confirmed by a plasma FSH level of >40 IU/L at screening
? They have undergone surgically sterilization at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and/or Principal In

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Adjunctive therapy to standard-of-care for the treatment of posterior uveitis or panuveitis secondary to Behçet's disease
MedDRA version: 12.0 Level: LLT Classification code 10036370 Term: Posterior uveitis

Intervention(s)

Product Name: AIN457
Product Code: AIN457
Pharmaceutical Form: Powder for solution for injection
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: Main objective:

To determine the efficacy of subcutaneous AIN457 compared to placebo in reducing the rate of recurrent ocular exacerbations in Behçet’s patients with posterior uveitis or panuveitis who are receiving standard-of-care immunomodulatory therapy.

Primary end point(s): The primary efficacy variable is the rate of recurrent ocular exacerbations of posterior uveitis or panuveitis in the study eye during the 24 weeks of study treatment. For the primary analysis, the primary efficacy variable will be transformed into the ordered categories

Secondary Objective: objectives:
Determine if subcutaneous AIN457 reduces need for standard-of-care immunosuppressive medications in patients requiring systemic immunosuppression to treat or prevent posterior uveitis or panuveitis secondary to Behçet’s disease.
Assess safety of targeted IL-17 inhibition with AIN457 in patients with posterior or panuveitis secondary to Behçet’s disease receiving standard-of-care immunomodulatory therapy
To determine the effect of subcutaneous AIN457 on macular edema and visual acuity .
To establish the impact of AIN457 on quality of life.
To observe the effect of AIN457 on the systemic non-ocular manifestations of Behçet’s disease.
To observe the effect of AIN457 on retinal vascular leakage and macular edema as determined by fluorescein angiography

Secondary ID(s)

not available

CAIN457C2303