Clinical trial NCT03554161: Tocilizumab for the Treatment of Refractory Behcet's Uveitis
Official title: Efficacy and Safety of Tocilizumab in the Treatment of Refractory Uveitis in Patients With Behcet's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Behcet Syndrome
Uveitis
Keywords: Tocilizumab
Refractory uveitis
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2018-06-13
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Tocilizumab is approved for the treatment of several inflammatory disease, this study tends to evaluate the response to TCZ in refractory BDU, thus it is a self-control study.
Primary purpose: TREATMENT

Brief summary: The aim of this single-center prospective study is to evaluate the efficacy and safety of Tocilizumab (TCZ), humanized monoclonal antibody against IL-6receptor, in the treatment of refractory Uveitis of Behçet's disease (BDU), to verify its effects on decreasing the dose of cortical steroids, and to determine whether it can reduce BDU recurrence.

Detailed description: Uveitis of Behçet's disease (BDU) is the most common form of ocular manifestations, which is also the leading cause of irreversible visual impairment. The aim of the study is to Improve treatment strategy of the disease as well as to reduce blindness.

Tocilizumab (TCZ) is a humanized antibody against IL-6 receptor, clinical trials on non-infectious uveitis and retrospective study on BDU has obtained expected results.

This single-center prospective study is to evaluate the efficacy and safety of TCZ in the treatment of refractory BDU, to verify its effects on decreasing the dose of corticosteroids, and to determine whether it can reduce BDU recurrence.The investigators aim to enroll nine refractory BDU patients with acute onset uveitis, with difficulty tapering corticosteroids while being treated with at least one of the commonly used immunosuppressants. All participants will receive TCZ , oral corticosteroids and immunosuppressants will remain unchanged, intraocular injection will be avoided. During monthly follow-up, the investigators will measure and record intraocular inflammation status，as well as extraocular manifestations and the acute-phase reactants. The participants will continue to receive TCZ for six months, the primary end point is the efficacy four weeks after first dose of TCZ, secondary end points other than intraocular inflammation will be achieved on each follow-up visit, as quality of life improvements, side effects, recurrence of uveitis, and corticosteroids-tapering effects.

On statistical analysis, the self-control treatment efficiency and recurrence rate difference will be determined using T-test of paired samples at a significance level of 0.05(2-sided).

To ensure the interest of the participants, the study has been reviewed by the PUMCH ethics committee, and drug clinical research liability insurance was prepared.

Eligibility criteria: Inclusion Criteria:

* All participants fulfill the the proposed International Criteria for BD, either ISG criteria(1990) or ICBD criteria(2013).
* All participants present with refractory BDU , acute onset uveitis, either posterior segment involvement or panuveitis, with difficulty tapering corticosteroids while being treated with at least one of the commonly used immunosuppressants, without severe extraocular manifestations.

Exclusion Criteria:

* Patients with impaired hepatic and renal function, other severe ocular diseases, active tuberculosis, viral hepatitis, malignancy, pregnancy will be excluded.

Primary outcomes:
measure: Efficacy of Tocilizumab on BD Uveitis
timeFrame: four weeks
Secondary outcomes:
measure: Intraocular inflammation evaluation BOS24 index
timeFrame: each follow-up visit / every four weeks, up to six months
measure: Corticosteroid-tapering effects
timeFrame: six months
measure: Reduction of uveitis recurrence
timeFrame: each follow-up visit / every four weeks, up to six months
measure: Severity of uveitis on recurrence
timeFrame: each follow-up visit / every four weeks, up to six months
measure: Improvement of quality of life
timeFrame: each follow-up visit / every four weeks, up to six months
measure: Improvement of quality of life
timeFrame: each follow-up visit / every four weeks, up to six months
measure: Side effects of treatment
timeFrame: each follow-up visit / every four weeks, up to six months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Department of Rheumatology, Peking Union Medical College Hospital
name: Wenjie Zheng, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Atienza-Mateo B, Calvo-Rio V, Beltran E, Martinez-Costa L, Valls-Pascual E, Hernandez-Garfella M, Atanes A, Cordero-Coma M, Miquel Nolla J, Carrasco-Cubero C, Loricera J, Gonzalez-Vela MC, Vegas-Revenga N, Fernandez-Diaz C, Demetrio-Pablo R, Dominguez-Casas LC, Luis Martin-Varillas J, Palmou-Fontana N, Hernandez JL, Gonzalez-Gay MA, Blanco R. Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behcet's disease: multicentre retrospective study. Rheumatology (Oxford). 2018 May 1;57(5):856-864. doi: 10.1093/rheumatology/kex480.
citation: Lopalco G, Fabiani C, Sota J, Lucherini OM, Tosi GM, Frediani B, Iannone F, Galeazzi M, Franceschini R, Rigante D, Cantarini L. IL-6 blockade in the management of non-infectious uveitis. Clin Rheumatol. 2017 Jul;36(7):1459-1469. doi: 10.1007/s10067-017-3672-z. Epub 2017 May 20.