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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Bordeaux

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

28 Apr 2023 → 4 Nov 2025

Decision date (initial)

2024-07-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512766-34-00

EudraCT number

2018-004536-29

ClinicalTrials.gov

NCT04237103

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the efficacy of the combination of methotrexate (MTX) (Per Os) at 15mg/week + TL01 UVB phototherapy in a population of adult patients with progressive vitiligo, by estimating the percentage of repigmented area at 8 months using the VASI score in the experimental group receiving MTX + TL01 UVB phototherapy.

Secondary objectives 5

1. To assess the clinical and biological safety of the combination of MTX (PO 15mg/week) + UVB TL01.
2. Estimate the percentage of repigmented area in the calibration group (Placebo + UVB TL01) using the VASI score at Month 8.
3. Estimate the percentage of repigmented area using the VETF and VES scores in both groups at Month 4 and Month 8
4. To assess the improvement in quality of life score and disease burden measured using the Dermatology Life Quality Index (DLQI), the Vitiligo Impact Patient scale (VIPs) and SkinDex29 questionnaires in both groups at Month 4 and Month 8.
5. Evaluate the reduction in inflammatory markers (blood and skin) in both groups at Month 4 and Month 8

Conditions and MedDRA coding

Vitiligo with new lesions or extension of old lesions during the last 6 months

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Subject male or female age over 18 years old
2. Diagnosis of non-segmental (symmetrical) vitiligo with body surface area ≥10%
3. 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.
4. Signed informed consent document
5. 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
6. 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
7. Patient registered to the French Social Security

Exclusion criteria 25

1. Segmental or mixed vitiligo
2. 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 Summary of the Product Characteristics (SmPC)
3. Intake of restricted medications 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
4. 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
5. High alcohol intake defined as more than 60 g of daily intake (approx daily intake of 0.5 l of wine or equivalent),
6. Patients who have a known allergy or hypersensitivity to MTX
7. Patients who have a known serious adverse event to MTX prior to the trial leading to MTX discontinuation in the past
8. 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
9. 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:
10. Total white blood cell count <3G/L
11. Neutrophil count < 1.5 G/l
12. Lymphocytes count < 0.5G/l
13. Platelet count < 100 G/l
14. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)>3 times the upper limit of normal (ULM)
15. Hemoglobin <8.5g/dL (85.0 g/L)
16. Creatinine clearance <40ml/min (Cockcroft formula)
17. For women: pregnant or breast feeding
18. 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,
19. Patients who have primary or secondary active immunodeficiency
20. Patients who had live vaccine administration within 4 weeks prior to baseline
21. 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)
22. Patients who had history of malignancy within 5 years prior to the trial that could contraindicate the use of an immunosuppressant
23. Patients who will not be available for protocol which require study visits or procedures
24. Patients who is not affiliated to the French Social Security system
25. Patients unable to give informed consent and/or comply with all required study procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluation of reduction in the VASI score in the experimental group receiving MTX + UVB TL01 assessed 8 months after the start of treatment.

Secondary endpoints 7

1. Evaluation of VASI score reduction at M4
2. Evaluation of clinical and biological measures of MTX and phototherapy safety at M4 and M8
3. Evaluation of VETF score variation
4. Evaluation of F-VASI score variation
5. Evaluation of F-VASI score variation
6. Evaluation of variation in the DLQI (Dermatology Quality of Life Index) score
7. Assessment of variations in blood and skin inflammatory parameters: ELISA on serum at baseline, M2, M4 and M8

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

Sponsor organisation

Centre Hospitalier Universitaire De Bordeaux

Address

12 Rue Dubernat, Cs 91286 Cs 91286

City

Talence

Postcode

33400

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Coordinating investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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