TOCILIZUMAB for Behçet's disease-associated uveitis|Behçet's disease

Inclusion criteria

• {"criterion_text":"- Age >= 18 at Inclusion\n- Affiliation to a social security system. Patients affiliated to universal medical coverage (CMU) are eligible for the study\n- Provide written, informed consent prior to the performance of any study-specific procedures\n- Diagnosis of Behçet’s disease according to the International Criteria for Behçet's Disease (ICBD) (see appendix 18.2) or history of aphtosis\n- Diagnosis of non-infectious intermediate, posterior-, or pan-uveitis in at least one eye fulfilling the International Study Group Classification Criteria (Standardization of Uveitis Nomenclature [SUN] criteria) of posterior, or pan- uveitis\n- Sight threatening uveitis defined according to the validated international definition as 2 lines of drop in visual acuity on a 10/10 scale, and/or retinal inflammation (macular oedema and/or retinal vasculitis).\n- Chest X-ray (postero-anterior and lateral) or CT-scanner results within 12 weeks prior to Inclusion with no evidence of active Tuberculosis, active infection, or malignancy\n- For female subjects of child-bearing potential (premenopausal female capable of becoming pregnant), a negative serum pregnancy test (plasmatic or urinary)\n- For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject’s partner from becoming pregnant during the study and 3 and 5 months after stopping therapy for tocilizumab and adalimumab, respectively.\n- Negative TB test obtained within 12 weeks prior to inclusion. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test) is eligible if her/his chest X-ray does not show evidence suggestive of active TB disease and there are no clinical signs and symptoms of pulmonary and/or UVB protocol, version 5.0 of 02/04/2024 31/76 This document is the property of DRCI/AP-HP. All reproduction is strictly prohibited extra-pulmonary TB disease. These subjects with a latent TB infection who have not already received a prophylactic TB treatment must agree in advance to complete such a treatment course. The treatment should be started at the latest at inclusion"}

Exclusion criteria

• {"criterion_text":"- Infectious uveitis, masquerade syndromes, or uveitis due to causes other than BD uveitis\n- History of intestinal ulceration or diverticulitis\n- Known porphyria\n- Laboratory values assessed during Inclusion: a. Neutrophil < 1.0 x 10^3/mm3 ; b. Platelet count < 80x 10^3/mm3 ; c. ASAT or ALAT > 5 ULN\n- Treatment with anti-TNF and/or Tocilizumab therapy within 1 month prior to inclusion\n- Patient on azathioprine, mycophenolate mofetil, or methotrexate at the time of inclusion (these drugs must be withdrawn prior to receiving the tocilizumab or adalimumab dose on Day 0).\n- Stage III and IV New York Heart Association (NYHA) cardiac insufficiency\n- Severe renal (Glomerular filtration rates (GFR) <30ml/min) or liver insufficiency (prothrombin <50% without other causes)\n- Any live (attenuated) vaccine within 30 days prior to inclusion\n- Breastfeeding and pregnant women\n- Active tuberculosis or history of untreated tuberculosis and/or severe infection\n- Positive HIV antibody and/or positive hepatitis B surface antigen and/or positive hepatitis C RNA, results obtained within 1 month prior to inclusion\n- History of malignancy within 5 years prior to Inclusion other than carcinoma in situ of the cervix, non-metastatic squamous or basal cell carcinoma of the skin\n- History of severe allergic or anaphylactic reactions to monoclonal antibodies\n- History of multiple sclerosis and/or demyelinating disorder\n- Hypersensitivity to the active substance or an excipient of the IMP or the auxiliary medicine\n- Active or suspected ocular infection\n- Infection oculaire active suspectée"}

Primary endpoints

• {"endpoint_text":"- Efficacy will be defined by a complete remission of ocular involvement with prednisone (or prednisolone, only if prednisone is out of stock in the market) lower or equal to 5 mg/day at W16 after randomization. Complete remission of ocular inflammation will be defined as complete resolution of retinal vasculitis and/or macular edema with prednisone (or prednisolone, only if prednisone is out of stock) lower or equal to 5 mg/day at W16. In patients with bilateral uveit","definition_or_measurement_approach":"Complete remission defined as complete resolution of retinal vasculitis and/or macular edema with prednisone (or prednisolone if prednisone unavailable) ≤ 5 mg/day at Week 16 after randomization; assessment based on ophthalmologic examination and imaging (as described in protocol)."}

Secondary endpoints

• {"endpoint_text":"- Measures of corticosteroid sparing (e.g., percent meeting targets [lower than 0.1 mg/day/kg of prednisone (or prednisolone, only if prednisone is out of stock in the market)], mean dose at week 16, and cumulative dose).\n- Time to response onset\n- Measures of acute-phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], at week 4, 8, 12, 16, 24, 36 and 48\n- Rate and Time to occurrence of relapse or worsening while on study. (Relapse will be defined as the reappearance of clinical and/or paraclinical features of active disease or by the occurrence of new lesions or progression of preexisting lesions).\n- Changes in Behcet’s Disease Current Activity Form (BDCA) at week 8, 16 and 24\n- Changes in Behcet’s Syndrome Activity Score (BSAS) at week 16\n- Changes in other organs involved by BD at week 4, 8, 12, 16, 24, 36 and 48\n- Changes in quality of life (QOL) (SF36v2 TM Health Survey) and Behcet’s Disease Quality of Life Measure (BD-QoL) at week 16 and 24\n- Safety and tolerability of treatments in BD patients as assessed by frequency and severity of adverse clinical events at week 4, 8, 12, 16, 24, 36 and 48\n- Time to treatment failure (time to occurence)\n- Changes in Tyndall, flare and Vitreous Haze at week 8, 16, 24, 36 and 48\n- Changes in Best corrected visual acuity (SNELLEN score) at week 8, 16, 24, 36 and 48\n- Changes in central retinal thickness measured with Optical Coherence Tomography (OCT) at week 8, 16, 24, 36 and 48\n- Percentage of patients with central retinal thickness <300 microns at week 8, 16, 24, 36 and 48\n- Percentage of patients without retinal vessel leakage on retinal angiography at week 16, and at week 24, 36 and 48, in case of retinal vasculitis","definition_or_measurement_approach":"Endpoints measured using clinical assessments, laboratory markers (ESR, CRP), imaging (OCT, retinal angiography), standardized scores/questionnaires (BDCA, BSAS, SF-36, BD-QoL), and adjudicated definitions for relapse and treatment failure; timepoints specified in each endpoint (weeks 4, 8, 12, 16, 24, 36, 48 where indicated)."}

France

Earliest CTIS Part Ii Submission Date

24-04-2024

Latest Decision Or Authorization Date

11-07-2025

Processing Time Days

443

Number Of Sites

27

Number Of Participants

60

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"PHRC National 2019 - Ministère des solidarités et de la Santé","duties_or_roles":"Source of monetary support","organisation_type":""}