The Evaluation of Vitiligous Lesions Repigmentation After Topical Administration of Methotrexate in Patients With Active Vitiligo (EVRAM)

The aim of this study is to evaluate the influence of two concentrations of methotrexate on vitiligous lesions in patients with non-segmental vitiligo

Study Overview

• Status: Completed
• Conditions: Non-segmental Vitiligo
• Intervention / Treatment: Drug: 1% Methotrexate gel; Drug: 0.5% Methotrexate gel

Detailed Description

Methotrexate, synthesized in the 1950s as an anticancer drug with an antiproliferative effect, is currently one of the most commonly used immunosuppressive agents in dermatology. The use of small, non-oncological doses has revealed its anti-inflammatory properties, including the impact on a number of cytokines involved in the pathogenesis of autoimmune diseases. It has been shown that treatment with methotrexate reduces the levels of TNF-alpha-producing T cells, while the number of IL-10 producing T cells increases. Methotrexate also inhibits the synthesis of interferon-γ. The above considerations justify the use of topical methotrexate in patients with vitiligo in order to obtain repigmentation.

A study has been designed as a single-center, randomized, double-blind, placebo-controlled pilot study with the enrollment of up to 100 active non-segmental vitiligo patients presenting with vitiligous lesions on both upper and lower limbs. Clinical effects of gel containing 1% methotrexate or 0.5% methotrexate applied on a preselected limb will be assessed in comparison with vehicle ointment applied on the opposite limb. All study participants will undergo clinical evaluation using Body Surface Area (BSA) and Vitiligo Area Scoring Index (VASI) scales at baseline, week 4, week 8 and week 12 time points. Precise assessment of skin lesions will be performed using photographic documentation obtained during each study visit and processed with NIS-Elements software.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Cuiavian-Pomeranian
    • Bydgoszcz, Cuiavian-Pomeranian, Poland, 85094
      • Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Faculty of Medicine in Bydgoszcz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients of Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz
2. Provision of an informed consent form prior to any study procedures
3. Diagnosis of non-segmental acrofacial vitiligo with upper and lower limbs involvement
4. Active vitiligo, defined as appearance of new areas of depigmentation or progression of existing areas of depigmentation within 3 months preceding screening
5. Male or non-pregnant and non-breastfeeding female patients aged 18 to 80 years
6. Women must use effective contraception one month preceding treatment, during treatment and 6 months after completing treatment.
7. Confirmed valid health insurance

Exclusion Criteria:

1. Diagnosis of segmental, mixed, unclassified or undefined vitiligo
2. Pregnancy and breastfeeding
3. Hypersensitivity to methotrexate or any of the excipients
4. Systemic immunosuppressive/immunomodulating i.e. cyclosporine A, corticosteroids within 4 weeks preceding eligibility screening or azathioprine, methotrexate, mycophenolate mofetil, Janus kinase - JAK within 8 weeks preceding eligibility screening
5. Phototherapy due to vitiligo or any other medical conditions within the 4-week period preceding eligibility screening
6. Any topical or systemic additional vitiligo treatment (e.g. antioxidants, ginkgo biloba, dermo-cosmetics) within 4 weeks preceding screening
7. Surgical treatment of vitiligous lesions within past 4 weeks
8. Severe liver dysfunction [bilirubin> 5 mg / dL (85.5 μmol / L)], including cirrhosis and hepatitis
9. Severe renal impairment (eGFR <20 ml / min),
10. Disorders of the hematopoietic system, bone marrow disorders (leukopenia, thrombocytopenia, anemia),
11. Immunodeficiencies, including HIV infection
12. Severe acute or chronic infections such as tuberculosis
13. Alcohol abuse
14. Mouth ulcers and known active gastric or duodenal ulcer disease
15. Recent surgical wounds.
16. Skin malignancies (currently or history of skin malignancy within 5 years preceding screening)
17. Presence of skin characteristics that may interfere with study assessments
18. Patients currently participating in any other clinical study
19. Uncooperative patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methotrexate 1% gel; 1% methotrexate gel applied onto a predefined limb	Drug: 1% Methotrexate gel; 1% methotrexate gel applied onto a predefined limb; Other Names: methotrexate
Active Comparator: Methotrexate 0.5% gel; 0.5% methotrexate gel applied onto a predefined limb	Drug: 0.5% Methotrexate gel; 0.5% methotrexate gel applied onto a predefined limb; Other Names: methotrexate
Placebo Comparator: Vehicle gel; Vehicle gel applied onto a predefined limb	Drug: 1% Methotrexate gel; 1% methotrexate gel applied onto a predefined limb; Other Names: methotrexate; Drug: 0.5% Methotrexate gel; 0.5% methotrexate gel applied onto a predefined limb; Other Names: methotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of repigmentation of vitiligous lesions achieved after the administration of 1% methotrexate or 0.5% methotrexate gels compared to vehicle gel after a 12-week study period	change from baseline in repigmentation on BSA scale at 12 weeks	12 weeks
evaluation of repigmentation of vitiligous lesions achieved after the administration of 1% methotrexate or 0.5% methotrexate gels compared to vehicle gel after a 12-week study period	change from baseline in repigmentation on VASI scale at 12 weeks	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of patients who achieved particular response rate as follows none 0%; poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% in each arm assessed as a relative reduction in BSA scale	number of: poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% responders in each arm assessed as a relative reduction in BSA scale	12 weeks
percentage of patients who achieved particular response rate as follows none 0%; poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% in each arm assessed as a relative reduction in VASI scale	number of: poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% responders in each arm assessed as a relative reduction in VASI scale	12 weeks
the association between disease duration and repigmentation rate in study arms	the association between disease duration and repigmentation rate in study arms	12 weeks
comparison of 1% methotrexate and 0.5% methotrexate gel efficacy between study participants	comparison of BSA scale change between study arms	12 weeks
comparison of 1% methotrexate and 0.5% methotrexate gel efficacy between study participants	comparison of VASI scale change between study arms	12 weeks
rate of adverse events during treatment as assessed by CTCAE v4.0	number of adverse events related to study treatment	12 weeks

Collaborators and Investigators

• Sponsor: Nicolaus Copernicus University
• Investigators: Principal Investigator: Rafał Czajkowski, Prof., Head of Chair and Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: June 2, 2021
• First Submitted That Met QC Criteria: June 19, 2021
• First Posted (Actual): June 29, 2021

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Pigmentation Disorders; Hypopigmentation; Vitiligo; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: WL107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No