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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen, Centre Hospitalier Universitaire Rouen

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

30 Aug 2023 → 26 Dec 2024

Decision date (initial)

2024-05-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-513802-77-00

EudraCT number

2022-000366-18

ClinicalTrials.gov

NCT05651880

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

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 objectives 7

1. To evaluate the partial remission rate at 1 month and 3 months
2. To evaluate the evolution of visual acuity at 1 month, 3 months and 6 months.
3. To evaluate the evolution of ocular inflammation at 1 month, 3 months and 6 months
4. To evaluate the evolution of retained vasculitis lesions at 1 month, 3 months, and 6 months
5. To evaluate the evolution of macular oedema at 1 month, 3 months and 6 months
6. To evaluate the evolution of corticosteroid dosage at 1 month, 3 months and 6 months
7. To evaluate the tolerance of the treatment

Conditions and MedDRA coding

Active non-anterior non-infectious uveitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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.
2. 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.
3. Patient of legal age who has read and understood the information letter and signed the consent form.
4. Patient affiliated to a social security plan.
5. Patient under 65 years old
6. 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)
7. 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
8. HIV, HCV and HBV serology with no active infection, less than 1 month old (1 month included)

Exclusion criteria 29

1. Isolated anterior uveitis
2. Infectious uveitis
3. Severe uveitis threatening the visual prognosis and requiring emergency treatment with intravenous corticosteroids
4. Initial visual acuity > 1.3 LogMAR in at least one eye.
5. Corneal or lens opacity that prevents fundus visualization or may require cataract surgery during the study.
6. Contraindication to baricitinib (OLUMIANT 2 and 4 mg film-coated tablets): Hypersensitivity to the active substance or to any of the excipients.
7. Contraindication to mydriasis.
8. Refractory glaucoma in either eye.
9. Monophthalmic patient.
10. Previous treatment with JAK inhibitors
11. 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.
12. 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.
13. Treatment with OAT3 inhibitors with high inhibitory potential such as probenecid, leflunomide, teriflunomide
14. Vaccination with a live vaccine or live attenuated vaccine within 15 days prior to inclusion
15. Risk factor for developing a malignancy (patient has or has had a malignancy)
16. Personal history of venous thromboembolic disease.
17. Presence of a hereditary coagulation disorder
18. Risk factors for major cardiovascular events (such as a history of heart attack or stroke)
19. Smokers or Former Long-term smokers
20. Pregnant or parturient or breastfeeding woman or lack of proven contraception
21. Obese patient with a body mass index ≥ 40 kg/m2
22. Hemoglobin < 8 g / dl
23. Platelet count <100,000 / mm3 or >500,000 / mm3
24. Neutrophil count <1000 / mm3, lymphocyte count <500/mm3.
25. Renal impairment with clearance <30 ml/min.
26. Severe hepatic impairment.
27. Allergy to fluorescein
28. Person deprived of liberty by an administrative or judicial decision or person placed under safeguard of justice / sub guardianship or curatorship.
29. Patient who has participated in another drug trial within 3 months prior to the start of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 9

1. Partial remission at 1 month, 3 months of treatment, according to the same parameters as defined for the primary endpoint.
2. Median change in visual acuity (LogMAR) at 1 month, 3 months and 6 months of treatment compared to baseline ophthalmologic assessment
3. Slit-lamp measurement of median change in anterior chamber inflammation according to the Tyndall, SUN (1) scale at 1 month, 3 months and 6 months of treatment compared to baseline ophthalmologic assessment
4. Slit-lamp measurement of median change in vitreous inflammation according to the vitreous haze (SUN [1]) at 1 month, 3 months, and 6 months of treatment compared with the initial ophthalmologic evaluation.
5. Fluorescein angiographic analysis of vasculitis lesions at 1 month, 3 months, and 6 months of treatment compared with the initial ophthalmologic evaluation
6. Optical coherence tomography measurement of median change in central macular thickness at 1 month, 3 months, and 6 months of treatment compared with the initial ophthalmologic evaluation.
7. Measurement of the number of patients with correction of cystoid macular edema measured by optical coherence tomography (cystoid macular thickness <300 μm and disappearance of intraretinal logettes) at 1 month, 3 months, and 6 months of treatment compared with the initial ophthalmologic assessment
8. Measurement of median change in corticosteroid dosages at 1 month, 3 months, and 6 months of treatment compared with the initial ophthalmologic evaluation
9. EvI and EvIG on baricitinib from initiation of treatment through 6 months of follow-up.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications