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

Primary Purpose

Non-segmental Vitiligo

Status
Completed
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
1% Methotrexate gel
0.5% Methotrexate gel
Sponsored by
Nicolaus Copernicus University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-segmental Vitiligo

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Faculty of Medicine in Bydgoszcz

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Methotrexate 1% gel

Methotrexate 0.5% gel

Vehicle gel

Arm Description

1% methotrexate gel applied onto a predefined limb

0.5% methotrexate gel applied onto a predefined limb

Vehicle gel applied onto a predefined limb

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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
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
comparison of 1% methotrexate and 0.5% methotrexate gel efficacy between study participants
comparison of BSA scale change between study arms
comparison of 1% methotrexate and 0.5% methotrexate gel efficacy between study participants
comparison of VASI scale change between study arms
the association between disease duration and repigmentation rate in study arms
the association between disease duration and repigmentation rate in study arms
rate of adverse events during treatment as assessed by CTCAE v4.0
number of adverse events related to study treatment

Full Information

First Posted
June 2, 2021
Last Updated
September 8, 2023
Sponsor
Nicolaus Copernicus University
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1. Study Identification

Unique Protocol Identification Number
NCT04942860
Brief Title
The Evaluation of Vitiligous Lesions Repigmentation After Topical Administration of Methotrexate in Patients With Active Vitiligo
Acronym
EVRAM
Official Title
The Evaluation of Vitiligous Lesions Repigmentation After Topical Administration of Methotrexate in Patients With Active Vitiligo
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
June 1, 2023 (Actual)
Study Completion Date
August 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nicolaus Copernicus University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-segmental Vitiligo

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methotrexate 1% gel
Arm Type
Active Comparator
Arm Description
1% methotrexate gel applied onto a predefined limb
Arm Title
Methotrexate 0.5% gel
Arm Type
Active Comparator
Arm Description
0.5% methotrexate gel applied onto a predefined limb
Arm Title
Vehicle gel
Arm Type
Placebo Comparator
Arm Description
Vehicle gel applied onto a predefined limb
Intervention Type
Drug
Intervention Name(s)
1% Methotrexate gel
Other Intervention Name(s)
methotrexate
Intervention Description
1% methotrexate gel applied onto a predefined limb
Intervention Type
Drug
Intervention Name(s)
0.5% Methotrexate gel
Other Intervention Name(s)
methotrexate
Intervention Description
0.5% methotrexate gel applied onto a predefined limb
Primary Outcome Measure Information:
Title
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
Description
change from baseline in repigmentation on BSA scale at 12 weeks
Time Frame
12 weeks
Title
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
Description
change from baseline in repigmentation on VASI scale at 12 weeks
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
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
Description
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
Time Frame
12 weeks
Title
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
Description
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
Time Frame
12 weeks
Title
comparison of 1% methotrexate and 0.5% methotrexate gel efficacy between study participants
Description
comparison of BSA scale change between study arms
Time Frame
12 weeks
Title
comparison of 1% methotrexate and 0.5% methotrexate gel efficacy between study participants
Description
comparison of VASI scale change between study arms
Time Frame
12 weeks
Title
the association between disease duration and repigmentation rate in study arms
Description
the association between disease duration and repigmentation rate in study arms
Time Frame
12 weeks
Title
rate of adverse events during treatment as assessed by CTCAE v4.0
Description
number of adverse events related to study treatment
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients of Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz Provision of an informed consent form prior to any study procedures Diagnosis of non-segmental acrofacial vitiligo with upper and lower limbs involvement Active vitiligo, defined as appearance of new areas of depigmentation or progression of existing areas of depigmentation within 3 months preceding screening Male or non-pregnant and non-breastfeeding female patients aged 18 to 80 years Women must use effective contraception one month preceding treatment, during treatment and 6 months after completing treatment. Confirmed valid health insurance Exclusion Criteria: Diagnosis of segmental, mixed, unclassified or undefined vitiligo Pregnancy and breastfeeding Hypersensitivity to methotrexate or any of the excipients 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 Phototherapy due to vitiligo or any other medical conditions within the 4-week period preceding eligibility screening Any topical or systemic additional vitiligo treatment (e.g. antioxidants, ginkgo biloba, dermo-cosmetics) within 4 weeks preceding screening Surgical treatment of vitiligous lesions within past 4 weeks Severe liver dysfunction [bilirubin> 5 mg / dL (85.5 μmol / L)], including cirrhosis and hepatitis Severe renal impairment (eGFR <20 ml / min), Disorders of the hematopoietic system, bone marrow disorders (leukopenia, thrombocytopenia, anemia), Immunodeficiencies, including HIV infection Severe acute or chronic infections such as tuberculosis Alcohol abuse Mouth ulcers and known active gastric or duodenal ulcer disease Recent surgical wounds. Skin malignancies (currently or history of skin malignancy within 5 years preceding screening) Presence of skin characteristics that may interfere with study assessments Patients currently participating in any other clinical study Uncooperative patients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rafał Czajkowski, Prof.
Organizational Affiliation
Head of Chair and Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Faculty of Medicine in Bydgoszcz
City
Bydgoszcz
State/Province
Cuiavian-Pomeranian
ZIP/Postal Code
85094
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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