Clinical trial NCT06327321: Vitiligo Treatment by Targeting TYK2 Mediated Responses
Official title: Vitiligo Treatment by Targeting TYK2 Mediated Responses Prospective Multicentric Double Blind Interventional Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Vitiligo, Generalized
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2024-03-25
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Vitiligo affects approximately 1 to 2% of the global population and significantly impacts people's quality of life. Achieving the best treatment outcomes for vitiligo involves addressing the autoimmune inflammatory response to stop the depigmentation process and promoting the differentiation of melanocyte stem cells to induce repigmentation. The loss of melanocytes in vitiligo is a result of an autoimmune process. While the IFN gamma pathway plays a crucial role in the adaptive immune response in vitiligo, there is increasing evidence highlighting the importance of the innate immune response. Deucravacitinib, an allosteric TYK2 inhibitor, has shown effectiveness and safety in treating psoriasis. It inhibits the responses of IFN alpha (IFNα), IFN beta (IFNβ), and IL12, and may also have an impact on the Th1 response. The hypothesis is that by targeting the IFN type I response and IL12, deucravacitinib could effectively halt the depigmentation process and facilitate repigmentation of vitiligo lesions. When combined with NB-UVB, the process of repigmentation should be significantly enhanced. The primary objective is to compare the proportion of patients treated with deucravacitinib versus placebo achieving VITIL-IA 50 at week 24.

Interventions Following central randomization, patients will be assigned to receive either deucravacitinib 12mg daily (QD) or a placebo daily (QD) for a duration of 24 weeks. At the end of this period, patients will be re-randomized to receive either deucravacitinib 12mg QD alone or deucravacitinib 12mg QD + twice weekly narrowband UVB treatment twice weekly for an additional 24 weeks.

Throughout the study, there will be a total of six visits conducted: selection, inclusion, Week 12, Week 24, Week 36, and Week 48. In patients who volunteer, a skin biopsy will be performed on both the lesional and peri-lesional areas at baseline, Week 12 and Week 36. Serum and plasma samples will be collected at the screening visit, Week 12, Week 24, Week 36, and Week 48.


Eligibility criteria: Inclusion Criteria:

1. Men and women with non-segmental vitiligo.
2. ≥ 18 and \<75 years
3. Patient with at least one lesion of more than 2 cm² not located on the face, hands or feet.
4. Patients with Vitil-IA score above 5% and T-VASI above 5% (not taking into account the involvement of hands and feet)
5. For women of child-bearing age, 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. A urine pregnancy test (βHCG in urines) will be performed.
6. Affiliation to a social security system
7. Signed informed consent
8. Patient willing and able to attend all study visits

Exclusion Criteria:

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.
2. Segmental or mixed vitiligo
3. Concomitant use of topical or systemic immunosuppressive medication or steroids
4. Patients suffering from photodermatosis or taking photosensitive drugs
5. Personal history of skin cancer
6. Personal history of cancer of less than 5 years
7. Patients with active infection
8. Tuberculosis or latent tuberculosis
9. Vulnerable people: pregnant or breast-feeding women, minors, adult under guardianship or deprived of freedom
10. Participants in other clinical therapeutic studies involving a drug that could interfere with the present evaluation

Primary outcomes:
measure: rate of depigmentation
timeFrame: at week 24
Secondary outcomes:
measure: number of patient with the T-VASI 50
timeFrame: at 48 weeks
Other outcomes:
Locations:
city: Nice
country: France
facility: CHU de Nice - Hôpital de l'Archet
state: Alpes-Maritimes
city: Paris
country: France
facility: APHP, Henri Mondor
state: Creteil
city: Bordeaux
country: France
facility: CHU de Bordeaux
state: Talence
city: Lille
country: France
facility: CHU de Lille
city: Lyon
country: France
facility: HCL
Study officials:
affiliation: CHU de Nice, Service de Dermatologie
name: PASSERON Thierry, PhD
role: PRINCIPAL_INVESTIGATOR
References: