Efficacy and Tolerance of Baricitinib, a JAK Inhibitor, in the Treatment of Refractory Non-infectious Non-anterior Uveitis (JAKUVEITE)

Phase 1

Conditions: Active non-anterior non-infectious uveitis
MedDRA version: 22.1Level: LLTClassification code: 10066681Term: Acute uveitis Class: 10015919
Therapeutic area: Diseases [C] - Eye Diseases [C11]

Registration Number: CTIS2024-513802-77-00

Lead Sponsor: Centre Hospitalier Universitaire Rouen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 33

Inclusion Criteria

Diagnosis of non-anterior non-infectious uveitis refractory to two lines of biotherapy (anti-TNF alpha and tocilizumab). Refractory uveitis is defined as: a. Either active uveitis, namely: anterior chamber inflammation >2+ [Tyndall, SUN scale (1)] and/or vitreous inflammation >2+ [Vitreous Haze, SUN scale (1)] and/or the presence of retinal vasculitides and/or the presence of cystoid macular edema (central macular thickness greater than strictly 300 µm measured on optical coherence tomography, associated with visualization of intraretinal logettes). b. or inactive uveitis but with corticosteroid dependence = 10 mg/day for at least 3 months., Need for discontinuation of biotherapy and conventional immunosuppressants (mycofenolate mofetil, methotrexate, azathioprine, cyclosporine, interferon alpha 2a) for at least 10 days prior to the inclusion date., Patient of legal age who has read and understood the information letter and signed the consent form., Patient affiliated to a social security plan., Patient under 65 years old, Female: a. Of childbearing age (defined by the CTFG as fertile, post-menarche to post-menopause, except in cases of permanent infertility): Using effective contraception (estrogen-progestin or intrauterine device or tubal ligation) for at least 4 weeks prior to inclusion, during treatment, and up to 1 week after cessation of treatment And, Presenting a negative urine pregnancy test at inclusion; b. Surgically infertile: no ovaries and/or uterus and/or bilateral salpingectomy; c. Menopausal: confirmatory diagnosis (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit), Negative quantiferon less than 6 months old (6 months included) and normal chest x-ray less than 3 months old (3 months included) or positive quantiferon in patients with a history of previously treated latent TB according to current recommendations, HIV, HCV and HBV serology with no active infection, less than 1 month old (1 month included)

Exclusion Criteria

Isolated anterior uveitis, Previous treatment with JAK inhibitors, Intraocular corticosteroid injection (subconjunctival or laterobulbar) within 1 month prior to inclusion or placement of an intravitreal corticosteroid implant within 3 months prior to inclusion., Need for treatment with a biotherapy (anti-IL6, anti-IL6 receptor, anti-IL1, anti-IL12/IL23 anti-IL17, anti-BAFF) for extra-ocular involvement, during the entire study period., Treatment with OAT3 inhibitors with high inhibitory potential such as probenecid, leflunomide, teriflunomide, Vaccination with a live vaccine or live attenuated vaccine within 15 days prior to inclusion, Risk factor for developing a malignancy (patient has or has had a malignancy), Personal history of venous thromboembolic disease., Presence of a hereditary coagulation disorder, Risk factors for major cardiovascular events (such as a history of heart attack or stroke), Smokers or Former Long-term smokers, Infectious uveitis, Pregnant or parturient or breastfeeding woman or lack of proven contraception, Obese patient with a body mass index = 40 kg/m2, Hemoglobin < 8 g / dl, Platelet count <100,000 / mm3 or >500,000 / mm3, Neutrophil count <1000 / mm3, lymphocyte count <500/mm3., Renal impairment with clearance <30 ml/min., Severe hepatic impairment., Allergy to fluorescein, Person deprived of liberty by an administrative or judicial decision or person placed under safeguard of justice / sub guardianship or curatorship., Patient who has participated in another drug trial within 3 months prior to the start of the study., Severe uveitis threatening the visual prognosis and requiring emergency treatment with intravenous corticosteroids, Initial visual acuity > 1.3 LogMAR in at least one eye., Corneal or lens opacity that prevents fundus visualization or may require cataract surgery during the study., Contraindication to baricitinib (OLUMIANT 2 and 4 mg film-coated tablets): Hypersensitivity to the active substance or to any of the excipients., Contraindication to mydriasis., Refractory glaucoma in either eye., Monophthalmic patient.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of baricitinib, a JAK1 and 2 inhibitor, in the management of non-infectious non-anterior uveitis multi-refractory to two lines of biotherapy (anti-TNF alpha and tocilizumab) after 6 months of treatment;Secondary Objective: To evaluate the partial remission rate at 1 month and 3 months, To evaluate the evolution of visual acuity at 1 month, 3 months and 6 months., To evaluate the evolution of ocular inflammation at 1 month, 3 months and 6 months, To evaluate the evolution of retained vasculitis lesions at 1 month, 3 months, and 6 months, To evaluate the evolution of macular oedema at 1 month, 3 months and 6 months, To evaluate the evolution of corticosteroid dosage at 1 month, 3 months and 6 months, To evaluate the tolerance of the treatment;Primary end point(s): Partial remission at 6 months. In case of bilateral involvement, the eye with the most severe involvement will be the eye chosen for the study.

Secondary Outcome Measures