Vitiligo affects approximately 1 to 2% of the global population and significantly impacts people's quality of life. areas of high stress. Ritlecitinib, an orally administered inhibitor of JAK3 (Janus kinase)/ TEC (tyrosine kinase expressed in hepatocellular carcinoma) has shown effectiveness and safety for the treatment of vitiligo. In a phase 2b trial, three doses of ritlecitinib, 200/50 mg, 100/50 mg, and 50 mg, were all statistically significant versus placebo on the Facial Vitiligo Area Scoring Index (F-VASI) at week 24 in patients with active NSV. Considering that the immune process primarily contributes to depigmentation while ultraviolet (UV) radiation stimulates the differentiation and proliferation of melanocyte stem cells for re-pigmentation, the investigators propose that a combination therapy using ritlecitinib and narrowband UVB (nbUVB) could offer an optimal approach for treating vitiligo patients.
The primary objective is thTo compare between the groups, the mean percentage change from baseline in F-VASI and T-VASI at week 52.
Following central randomization, patients will be assigned to receive either ritlecitinib 100mg daily (QD) or a combined therapy using ritlecitinib 100mg QD + twice weekly narrowband UVB treatment for a duration of 52 weeks. At the end of this period, all participants will continue for the open-label phase, receiving ritlecitinib 100mg QD. Eligible participants will be stratified by Fitzpatrick Skin Type (FST, also known as phototype). More specifically, there will be 2 strata based on FST targets: (1) FST I to III (2) FST I IV, to VI. Each FST stratum will target to enroll at least 50% participants into the study population. Stratified randomization across FST sub-groups will support the evaluation of a consistent benefit-risk profile across all FST strata. Enrollment of participants with active or stable nonsegmental vitiligo will be proactively managed without formally capping or stratifying.
Throughout the study, there will be a total of 8 visits conducted: selection, inclusion, week 4, week 12, week 24, week 36, week 52 and week 72. In patients who volunteer, a skin biopsy will be performed on both the lesional and perilesional areas at baseline, week 4 and week 52. We aim to include between 12 and 20 volunteer patients. Serum and plasma samples will be collected at the screening visit, week 4, week 12, week 24, week 36, week 52 and week 72.
A pregnancy test will be performed every 4 weeks i.e. at weeks 8, 16, 20, 28, 32, 40, 44, 48, 56, 60, 64 and 68;
1. Men and women with non-segmental vitiligo. 2. Age ≥ 18 age old 3. BSA involvement between 4% and 60% inclusive, excluding involvements at palms of the hands, soles of the feet, or dorsal aspect of the feet 4. BSA ≥0.5% involvement on the face (face is defined as including the area on the forehead to the original hairline, on the cheek vertically to the jawline, and laterally from the corner of the mouth to the tragus. The face will not include scalp, ears, neck, or surface area of the lips, but will include the nose and the eyelids) 5. F-VASI ≥0.5 and T-VASI ≥3 6. Active and stable vitiligo 7. For Women of childbearing potential (WOCBP), an effective contraception (estroprogestative pill, contraceptive implant, IUD, condoms or tubal ligation) should be used for more than one month before the inclusion in the study; Women of childbearing potential (WOCBP) must have a negative urine pregnancy test result at baseline; WOCBP are defined as women who are biologically capable of becoming pregnant, including women who are using contraceptives or whose sexual partners are either sterile or using contraceptives;
Have medically confirmed ovarian failure; or
Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause); 8. Affiliation to a social security system; 9. Signed informed consent.
1. Pregnant or breast-feeding women. Or women with potential childbearing and not taking contraceptives or who plan to get pregnant during the study duration, and 2. Segmental or mixed vitiligo, and 3. Contraindication to nbUVB phototherapy, and 4. Concomitant use of topical or systemic immunosuppressive medication or steroids, and 5. Patients treated before with oral JAK inhibitor, topical treatments (including JAK inhibitors) that could affect vitiligo (eg, corticosteroids, vitamin D3 and calcineurin inhibitor) within 2 Weeks of Day 1 (Baseline) and during the study
Use of permanent depigmentation treatment for vitiligo and/or other types of pigmentation disorder (eg, monobenzone or phenol).
Previous use of any systemic JAK inhibitor for any disease indication
Any non-B cell selective lymphocyte depleting agent (eg, alefacept, alemtuzumab) and alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc.
Parallel
LITFULO
DrugFollowing central randomization, patients will be assigned to receive either ritlecitinib 100mg daily (QD) or a combined therapy using ritlecitinib 100mg QD + twice weekly narrowband UVB treatment for a duration of 52 weeks. At the end of this period, all participants will continue for the open-label phase, receiving ritlecitinib 100mg QD. Eligible participants will be stratified by Fitzpatrick Skin Type (FST, also known as phototype).
LITFULO and UVB
Procedure/SurgeryFollowing central randomization, patients will be assigned to receive either ritlecitinib 100mg daily (QD) or a combined therapy using ritlecitinib 100mg QD + twice weekly narrowband UVB treatment for a duration of 52 weeks. At the end of this period, all participants will continue for the open-label phase, receiving ritlecitinib 100mg QD. Eligible participants will be stratified by Fitzpatrick Skin Type (FST, also known as phototype).
The Facial Vitiligo Area Scoring Index (F-VASI)
To compare the proportion of patients treated with combined ritlecitinib + nbUVB versus ritlecitinib monotherapy achieving The Facial Vitiligo Area Scoring Index (F-VASI) -75 at week.
Total Body Vitiligo Scoring Index (T-VASI) 50
To compare the proportion of patients treated with combined ritlecitinib + nbUVB versus ritlecitinib monotherapy achieving T-VASI50 at week 52
Safety treatment
All the adverse events (clinical and biological) occurring over the study period will be collected with their type, grade and severity. At each visit, the investigator will record all the events since the last visit
The quality of life
The quality of life will be assessed by using VIPs (Vitiligo Impact Patient scale) short form at baseline and week 36, week 52 and week 72. VIPs is a transcultural validated specific vitiligo burden tool according to skin phototype. The VIPs-22 which is the latest version of the scale will be used in this study. Evolution will be calculated between baseline and week 36, week 52 and week 72 considering the initial and second randomization to define different groups.
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