Clinical Trial: Efficacy and Safety of Ustekinumab, a Human Monoclonal Anti-IL-12/IL-23 Antibody, in Patients With Behçet Disease

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase 2 Open-Label Study to Evaluate the Efficacy and Safety of Ustekinumab, a Human Monoclonal Anti-IL-12/IL-23 Antibody, in Patients With Behçet Disease

Brief Summary: The purpose of this study is to evaluate the proof of concept of efficacy of ustekinumab in subjects with Behçet disease, including patients with oral ulcers (STELABEC-1) and patients with active posterior uveitis or panuveitis (STELABEC-2)

Detailed Summary:

Behçet disease (BD) is a chronic systemic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes. Two recent large genome-wide association studies (GWAS) conducted in Turkey and Japan reported association between single nucleotide polymorphism (SNP) of interleukin (IL)-10 and IL-23R/IL-12RB2 genes and BD. Interleukin-12 and interleukin-23, cytokines that induce naive CD4+ lymphocytes to differentiate into type 1 helper T cells (Th1 cells) and type 17 helper T cells (Th17 cells), respectively, have been identified as key mediators of BD. Promotion of Th1 and Th17 responses and suppression of regulatory T cells correlate with BD activity.

Due to the lack of an etiologic agent, the treatment is symptomatic without consensus. The goals are the functional recovery of a visceral involvement (eye, central nervous system) and prevention of relapse(s). The risks of BD are an increased mortality especially in case of arterial involvement, and a high morbidity due to the cumulative sequelae of ocular and neurological involvement. Steroids are the corner stone of the antiinflammatory agents administered topically or systemically. Relapses are frequently seen after discontinuation of steroids, and corticodependence is frequently observed leading to the use of immunosuppressive drugs.

Biologic agents that selectively block steps in the inflammatory cascade could provide additional therapies for BD.


Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome:

  • Number of oral ulcers at week 24 compared to baseline [ Time Frame: 24 weeks ]
    Treatment efficacy at week 24 for STELABEC-1 study on oral ulcers
  • Number of uveitis or retinal vasculitis remission [ Time Frame: 24 weeks ]
    Treatment efficacy at week 24 for STELABEC-2 study on eye involvement


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of oral and genital ulcers [ Time Frame: at baseline visit (week 0) ]
  • Number of oral and genital ulcers [ Time Frame: 4 weeks ]
  • Number of oral and genital ulcers [ Time Frame: 8 weeks ]
  • Number of oral and genital ulcers [ Time Frame: 12 weeks ]
  • Number of oral and genital ulcers [ Time Frame: 16 weeks ]
  • Number of oral and genital ulcers [ Time Frame: 24 weeks ]
  • Number of oral and genital ulcers [ Time Frame: 28 weeks ]
  • Number of oral and genital ulcers [ Time Frame: 40 weeks ]
  • Number of oral and genital ulcers [ Time Frame: 52 weeks ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: at baseline visit (week 0) ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: 4 weeks ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: 8 weeks ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: 12 weeks ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: 16weeks ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: 24 weeks ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: 28 weeks ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: 40 weeks ]
  • Pain Visual Analog Scales of oral and genital ulcers [ Time Frame: 52 weeks ]
  • Number of chorioretinal and/or inflammatory retinal vascular lesions, inflammation in anterior chamber and in vitreous haze [ Time Frame: baseline visit (week 0) ]
  • Number of chorioretinal and/or inflammatory retinal vascular lesions, inflammation in anterior chamber and in vitreous haze [ Time Frame: 4 weeks ]
  • Number of chorioretinal and/or inflammatory retinal vascular lesions, inflammation in anterior chamber and in vitreous haze [ Time Frame: 8 weeks ]
  • Number of chorioretinal and/or inflammatory retinal vascular lesions, inflammation in anterior chamber and in vitreous haze [ Time Frame: 12 weeks ]
  • Visual acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) [ Time Frame: 16 weeks ]
  • Number of chorioretinal and/or inflammatory retinal vascular lesions, inflammation in anterior chamber and in vitreous haze [ Time Frame: 24 weeks ]
  • Number of chorioretinal and/or inflammatory retinal vascular lesions, inflammation in anterior chamber and in vitreous haze [ Time Frame: 28 weeks ]
  • Number of chorioretinal and/or inflammatory retinal vascular lesions, inflammation in anterior chamber and in vitreous haze [ Time Frame: 40 weeks ]
  • Number of chorioretinal and/or inflammatory retinal vascular lesions, inflammation in anterior chamber and in vitreous haze [ Time Frame: 52 weeks ]
  • Behçet Syndrome Activity Score (BSAS) [ Time Frame: 12 weeks ]
  • Behçet Disease Current Activity Form (BDCAF) [ Time Frame: 12 weeks ]
  • Behçet Syndrome Activity Score (BSAS) [ Time Frame: 24 weeks ]
  • Behçet Disease Current Activity Form (BDCAF) [ Time Frame: 24 weeks ]
  • Behçet Syndrome Activity Score (BSAS) [ Time Frame: 52 weeks ]
  • Behçet Disease Current Activity Form (BDCAF) [ Time Frame: 52 weeks ]
  • Behçet Disease Quality of Life Measure : Short Form-36 (SF- 36) [ Time Frame: 12 weeks ]
  • Behçet Disease Quality of Life Measure : Routine Assessment of Patient Index Data 3 (RAPID3) [ Time Frame: 12 weeks ]
  • Behçet Disease Quality of Life Measure : Short Form-36 (SF- 36) [ Time Frame: 24 weeks ]
  • Behçet Disease Quality of Life Measure : Routine Assessment of Patient Index Data 3 (RAPID3) [ Time Frame: 24 weeks ]
  • Behçet Disease Quality of Life Measure : Short Form-36 (SF- 36) [ Time Frame: 52 weeks ]
  • Behçet Disease Quality of Life Measure : Routine Assessment of Patient Index Data 3 (RAPID3) [ Time Frame: 52 weeks ]
  • Number of adverse events [ Time Frame: from baseline visit up to 52 weeks ]
    adverse events including h

    Original Secondary Outcome: Same as current

    Information By: Assistance Publique - Hôpitaux de Paris

    Dates:
    Date Received: December 21, 2015
    Date Started: March 2017
    Date Completion: January 2019
    Last Updated: March 21, 2017
    Last Verified: March 2017