Evaluation of Baricitinib Efficacy in Refractory Non-Infectious Non-Anterior Uveitis: A Clinical Trial
- Trial ID
- 2024-513802-77-00
- Protocol
- 2020/420/HP
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of baricitinib, a JAK1 and JAK2 inhibitor, in the management of non-infectious non-anterior uveitis that is refractory to two lines of biotherapy, specifically anti-TNF alpha and tocilizumab, after 6 months of treatment. This is clinically relevant as it addresses a significant unmet need in patients with multi-refractory uveitis, potentially offering a new therapeutic option for those who have not responded to existing treatments.
Secondary objectives include:
- Evaluating the partial remission rate at 1 month and 3 months.
- Assessing the evolution of visual acuity at 1 month, 3 months, and 6 months.
- Monitoring the evolution of ocular inflammation at 1 month, 3 months, and 6 months.
- Evaluating the evolution of retained vasculitis lesions at 1 month, 3 months, and 6 months.
- Assessing the evolution of macular oedema at 1 month, 3 months, and 6 months.
- Evaluating the evolution of corticosteroid dosage at 1 month, 3 months, and 6 months.
- Assessing the tolerance of the treatment.
Participants
The clinical trial involves participants diagnosed with **active non-anterior non-infectious uveitis** that is refractory to two lines of biotherapy, specifically anti-TNF alpha and tocilizumab. The study population includes both male and female subjects under the age of 65, with a focus on individuals who are legally adults and have provided informed consent. Participants are required to have discontinued biotherapy and conventional immunosuppressants at least 10 days prior to inclusion. The trial includes individuals who are affiliated with a social security plan and have no active infections as confirmed by recent serology tests for HIV, HCV, and HBV. Female participants of childbearing potential must use effective contraception and present a negative pregnancy test at inclusion. The trial population is selected based on specific inclusion criteria, ensuring that participants have a confirmed diagnosis of refractory uveitis and meet health and lifestyle requirements. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **baricitinib**, a JAK1 and JAK2 inhibitor, in the management of non-infectious non-anterior uveitis that is refractory to two lines of biotherapy, specifically anti-TNF alpha and tocilizumab, after six months of treatment. This study is structured as a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thereby minimizing bias. The trial is expected to commence on June 1, 2024, and conclude by November 30, 2027, with a maximum treatment period of six months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as a diagnosis of non-anterior non-infectious uveitis refractory to previous treatments and the need for discontinuation of biotherapy and conventional immunosuppressants. Follow-up visits will occur at 1 month, 3 months, and 6 months to assess primary and secondary endpoints, including partial remission and changes in visual acuity, anterior chamber inflammation, vitreous inflammation, and central macular thickness. The end-of-study visit will evaluate the overall treatment efficacy and safety.
The expected length of participant involvement is approximately six months, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol. Participants will be monitored for safety and efficacy throughout the trial, with specific attention to any changes in corticosteroid dosages and the correction of cystoid macular edema. The trial aims to provide comprehensive data on the potential benefits of baricitinib in treating this challenging condition.
Treatment
The clinical trial involves the administration of **Olumiant** in two different dosages as the experimental medication. **Olumiant 4 mg film-coated tablets** contain the active substance **baricitinib**, a **JAK1 and JAK2 inhibitor**. The pharmaceutical form is a film-coated tablet, and the medication is administered orally. The maximum daily dose is 4 mg, with a total maximum dose of 720 mg over a treatment period of 6 months. The medication is manufactured by ELI LILLY NEDERLAND B.V. and is not a paediatric formulation.
Additionally, **Olumiant 2 mg film-coated tablets** are used, also containing **baricitinib**. This formulation is similarly administered orally, with a maximum daily dose of 2 mg and a total maximum dose of 360 mg over the same 6-month period. This product is also manufactured by ELI LILLY NEDERLAND B.V. and is not intended for paediatric use.
As part of the auxiliary treatments, **CORTANCYL 5 mg, comprimé sécable** is included, containing the active substance **prednisone**. This medication is in tablet form and is administered orally. The maximum daily dose is 1.2 mg/kg, with a total maximum dose of 216 mg/kg over a 6-month period. The manufacturer is CHEPLAPHARM ARZNEIMITTEL GMBH.
Another auxiliary treatment is **FLUOCYNE 10%, solution injectable I.V.**, which contains **fluorescein sodium**. This solution is intended for intravenous administration, with a maximum daily dose of 0.5 g and a total maximum dose of 2 g over a 4-week period. The product is manufactured by SERB.
Lastly, **FLUORESCEINE SODIQUE FAURE 10 POUR CENT, solution injectable** is used, also containing **fluorescein sodium**. This solution is administered via intravenous injection, with the same dosing schedule as FLUOCYNE 10%. The manufacturer is SERB SA. Both fluorescein sodium solutions are not paediatric formulations and are used as auxiliary treatments in the trial.
Efficacy
The efficacy of **baricitinib** in the treatment of refractory non-infectious non-anterior uveitis will be assessed through a series of primary and secondary endpoints. The primary endpoint is defined as partial remission at 6 months, with the eye exhibiting the most severe involvement being selected for evaluation in cases of bilateral involvement. Secondary endpoints include partial remission at 1 month and 3 months, median change in visual acuity (LogMAR) at 1 month, 3 months, and 6 months, and slit-lamp measurements of median change in anterior chamber inflammation and vitreous inflammation according to the Tyndall and SUN scales at the same timepoints. Additionally, fluorescein angiographic analysis of vasculitis lesions, optical coherence tomography measurements of median change in central macular thickness, and the number of patients with correction of cystoid macular edema will be evaluated at 1 month, 3 months, and 6 months. The median change in corticosteroid dosages will also be measured at these intervals. These assessments will be compared to baseline ophthalmologic evaluations to determine the efficacy of the treatment.
Inclusion and Exclusion Criteria
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
- Infectious uveitis
- 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.
- 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
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 01 Jun 2024 | 33 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Olumiant 4 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 4 | 6 | PRD4760225 |
Olumiant 2 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 2 | 6 | PRD4760217 |
CORTANCYL 5 mg, comprimé sécable | Other | COMPRIMÉ SÉCABLE | ORAL USE | 1.2 | 6 | PRD9995015 |
FLUOCYNE 10%, solution injectable I.V. | Other | SOLUTION INJECTABLE I.V. | INTRAVENOUS ADMINISTRATION | 0.5 | 4 | PRD345648 |
FLUORESCEINE SODIQUE FAURE 10 POUR CENT, solution injectable | Other | SOLUTION INJECTABLE | INTRAVENOUS INJECTION | 0.5 | 4 | PRD1924190 |