Clinical trial NCT04237103: Combination of Methotrexate and Phototherapy Versus Phototherapy in Adults with Progressive Vitiligo
Official title: Efficacy and Tolerance of the Combination of Methotrexate and Phototherapy Versus Phototherapy in Adults with Progressive Vitiligo: a Randomized Double-blind Prospective Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Vitiligo
Keywords: vitiligo
pigmentation
phototherapy
methotrexate
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2020-01-23
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Methotrexate taken orraly once a weekcombination with UVB TL01 in a population of adult patients with progressive vitiligo
Primary purpose: TREATMENT

Brief summary: This is a phase 2, randomized, double blind, multicenter study evaluating the efficacy and safety of the combination of methotrexate plus UVB TL01 in vitiligo.

Detailed description: Treatment Strategy: Multicentric, parallel double blind randomized phase 2 prospective study comparing MTX taken orally once a week + narrowband UVB TL01 versus placebo + narrowband UVB TL01 Follow-up of the study: patients included in this study will start MTX 2 months before starting narrowband UVB TL01. Phototherapy will be performed twice a week during 6 months. Follow-up visit will be done at month 2, 4 and month 8. Phone calls to the patient will be done at month 6

Eligibility criteria: Inclusion Criteria:

* Subject male or female age over 18 years old
* Diagnosis of non-segmental (symmetrical) vitiligo with body surface area ≥10%
* Active non-segmental vitiligo defined by Non-segmental vitiligo with new patches or extension of old lesions during the last 6 months AND Presence of hypochromic aspect under Wood's lamp examination and/or perifollicular hypopigmentation under Wood's lamp examination.
* Signed informed consent document
* Male patients agreeing to use a reliable method of birth control during the study i. e. preservative and for at least 6 months following the last dose of investigational product, the patient's partner treated by methotrexate must be notified of the teratogenic risk of methotrexate and should be under effective contraception throughout the study and for at least 6 months following the last dose of investigational product.
* Women of childbearing potential who are negatively tested for pregnancy and agree to use a reliable method of birth control (every month) or remain abstinent during the study and for at least 6 months following the last dose of investigational product. Methods of contraception considered acceptable include oral contraceptives, contraceptive patch, intrauterine device, vaginal ring
* Patient registered to the French Social Security

Exclusion Criteria:

* Segmental or mixed vitiligo
* Patients who have known active liver disease (with the exception of a simple liver steatosis, transaminases and/or alkaline phosphatases \> 2 ULM ) or history of liver disease in the past 2 years, whatever the related diagnosis but which could interfere with MTX safety and according to the summary of the SmPC.
* Intake of restricted medications (cf section VIII.5.) or other drugs considered likely to interfere with the safe conduct of the study, as assessed by the investigator and according to the Summary of the Product Characteristics (SmPC), including any drug intakes that could interfere with methotrexate metabolism or that could enhance liver and /or hematologic toxicity and according to the SmPC
* Patient with evidence or positive test for HIV, Hepatitis C virus, Hepatitis B virus (patients who are negative for hepatitis B surface antigen but positive for anti-hepatitis B anti body (HBsAb+ and HBcAb+) and negative for serum HBV DNA may participate in the study
* High alcohol intake defined as more than 60 g of daily intake (approx daily intake of 0.5 l of wine or equivalent),
* Patients who have a known allergy or hypersensitivity to MTX
* Patients who have a known serious adverse event to MTX prior to the trial leading to MTX discontinuation in the past
* Presence of significant hematologic or renal disorder or abnormal laboratory values at screening that, in the opinion of the investigator is associated with an unacceptable risk to the patient to participate in the study
* Clinical laboratory test results at screening that are outside a normal reference rating for the population and are considered clinically significant, or/and have any of the following specific abnormalities:
* Total white blood cell count \<3G/L
* Neutrophil count \< 1.5 G/l
* Lymphocytes count \< 0.5G/l
* Platelet count \< 100 G/l
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)\>3 times the upper limit of normal (ULM)
* Hemoglobin \<8.5g/dL (85.0 g/L)
* Creatinine clearance \<40ml/min (Cockcroft formula)
* For women: pregnant or breast feeding
* Patients who have an active or serious infection or history of infections (bacterial, viral, fungal or mycobacteria), requiring hospitalization or intra venous anti-infectives infusion within 4 weeks prior to the baseline,
* Patients who have primary or secondary active immunodeficiency
* Patients who had live vaccine administration within 4 weeks prior to baseline
* Patients who had already been treated by at least 250 sessions of phototherapy - Patients who have any current or active cancer (with the exception of patient with successfully treated with in situ cervix carcinoma)
* Patients who had history of malignancy within 5 years prior to the trial that could contraindicate the use of an immunosuppressant
* Patients who will not be available for protocol which require study visits or procedures
* Patients who is not affiliated to the French Social Security system
* Patients unable to give informed consent and/or comply with all required study procedures

Primary outcomes:
measure: Score with VASI formule
timeFrame: month 8
Secondary outcomes:
measure: Score with VASI formule
timeFrame: month 4
measure: Number of Adverse Events (AE) and serious adverse events (SAE), as well as the proportion of discontinuation due to AEs and/or SAEs
timeFrame: Month 8
measure: Evaluation of score Vitiligo European Task Force (VETF)
timeFrame: Month 4
measure: Evaluation of score Vitiligo European Task Force (VETF)
timeFrame: Month 8
measure: Evaluation of score of the Vitiligo Extent Score (VES)
timeFrame: Month 4
measure: Evaluation of score of the Vitiligo Extent Score (VES)
timeFrame: Month 8
measure: Evaluation of score of the Dermatology Life Quality Index (DLQI)
timeFrame: Month 4
measure: Evaluation of score of the Dermatology Life Quality Index (DLQI)
timeFrame: Month 8
measure: Evaluation of the score of the Skindex 29
timeFrame: Month 4
measure: Evaluation of the score of the Skindex 29
timeFrame: Month 8
measure: Evaluation of the score of the Vitiligo Impact Scale (VIP)
timeFrame: Month 4
measure: Evaluation of the score of the Vitiligo Impact Scale (VIP)
timeFrame: Month 8
measure: Evaluation of blood inflammatory markers using immunofluorescence on skin biopsies and ELISA multiplex.
timeFrame: Day 1
measure: Evaluation of skin inflammatory markers using immunofluorescence on skin biopsies and ELISA multiplex.
timeFrame: Day 1
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Service de Dermatologie - Hôpital Saint-André
city: Pau
country: France
facility: Centre Hospitalier de Pau
city: Périgueux
country: France
facility: Centre Hospitalier de Périgueux
city: Toulouse
country: France
facility: Service de Dermatologie - CHU de Toulouse - Hopital Purpan
Study officials:
affiliation: University of Bordeaux
name: Julien SENESCHAL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: