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Trial registered on ANZCTR


Registration number
ACTRN12623000682640
Ethics application status
Approved
Date submitted
1/06/2023
Date registered
26/06/2023
Date last updated
26/06/2023
Date data sharing statement initially provided
26/06/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The Efficacy and Safety of Deucravacitinib to that of Methotrexate, in Patients with Vulvar Lichen Planus who have Failed Topical Therapy with Potent Corticosteroids: A Randomized Controlled Trial
Scientific title
A Double-Blinded, Single-Centre, Randomized Controlled Clinical Trial to Compare the Efficacy and Safety of Deucravacitinib to that of Methotrexate, in Patients with Vulvar Lichen Planus who have Failed Topical Therapy with Potent Corticosteroids
Secondary ID [1] 308141 0
Bristol-Myers Squibb: IM011-1113
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vulvar Lichen Planus 327860 0
Condition category
Condition code
Skin 324944 324944 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will initially be treated with potent topical corticosteroids, Diprosone OV (Betamethasone Dipropionate 0.05% ointment in optimized vehicle) daily (0.5 to 1 fingertip unit [0.2-0.4 g]) to the affected areas on the vulva +/- vagina. At 8 weeks follow-up, the study investigators, who are dermatologists, will re-assess the participant’s genital erosive lichen planus (GELP) score. Responders (GELP<5) will be continued on Diprosone OV. Non-responders (GELP >=5), will be randomized 1:1 in a blinded fashion to receive:
(i) Intervention arm: Oral Deucravacitinib 6 mg tablet twice daily + Oral Placebo tablet (Microcrystalline Cellulose, Colloidal Silicon Dioxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate) weekly + Oral Folic acid 5mg weekly, or
(ii) Comparator arm: Oral Methotrexate 10mg tablet weekly + Oral Placebo tablet (Lactose monohydrate, Microcrystalline cellulose, Magnesium stearate, Opadry II) twice daily + Oral Folic acid 5mg weekly.
Diprosone OV will not be administered regularly in the non-responder group from week 8 onwards, but will be available on PRN (as needed) basis.
Participants will be asked to return drug containers to monitor adherence.
The treatments will conclude in Week 32.
Intervention code [1] 324597 0
Treatment: Drugs
Comparator / control treatment
Oral Methotrexate 10mg weekly + Oral Placebo tablet twice daily + Oral Folic acid 5mg weekly
(non-responders are randomized to either Deucravacitinib [intervention arm] or Methotrexate [comparator arm]).
Control group
Active

Outcomes
Primary outcome [1] 332755 0
The difference in mean change of GELP scores from baseline (week 8) to week 32 between Deucravacitinib and Methotrexate groups
Timepoint [1] 332755 0
Baseline (week 8 post-enrolment) to week 32 post-enrolment
Secondary outcome [1] 414605 0
Mean change in Vulvar Quality of Life Index (VQLI) scores
Timepoint [1] 414605 0
Weeks 8, 24, 32 post-enrolment
Secondary outcome [2] 414606 0
Weekly use of topical corticosteroid, collected from participant diary, and the number of 30-gram tubes used.
Timepoint [2] 414606 0
Throughout the study up to week 32 post-enrolment
Secondary outcome [3] 414607 0
Mean change in General Health Questionnaire-28 (GHQ-28) scores
Timepoint [3] 414607 0
Weeks 8, 24, 32 post-enrolment
Secondary outcome [4] 414608 0
Mean change in Physician Global Assessment (PGA) scores
Timepoint [4] 414608 0
Weeks 8, 24, 32 post-enrolment
Secondary outcome [5] 414609 0
Mean change in Patient Global Assessment (PtGA) scores
Timepoint [5] 414609 0
Weeks 8, 24, 32 post-enrolment
Secondary outcome [6] 414610 0
Immunological changes and expression of cytokines in serum and tissue. Each tissue sampling will involve taking two 3mm punch biopsies from the vulva.
The planned investigations include:
(i) Serum cytokine mRNA analysis involved in TYK-2 mediated pathway, e.g. IFN-Type I (IFN-a, IFN-b), IL-12, IL-23, IL-17.
(ii) Tissue cytokine mRNA analysis involved in TYK-2 mediated pathway, e.g. IFN-Type I (IFN-a, IFN-b), IL-12, IL-23, IL-17.
(iii) Immunohistochemistry with T-cell markers on tissue.
Timepoint [6] 414610 0
Serum: weeks 0 (enrolment), 8 and 32 post-enrolment.
Tissue: weeks 0 (enrolment), and 32 post-enrolment.

Eligibility
Key inclusion criteria
-Female
-18 years or older
-Histopathologically confirmed vulvar lichen planus (VLP), or fulfils diagnostic criteria developed by Wu et al. (2020) or Simpson et al. (2013)
-Moderate to severe VLP, determined by GELP score >=5, of which erythema and pain have to score >=1
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
-Those with a lichen sclerosus / lichen planus overlap.
-Patients receiving other systemic immune-modulating therapy within the previous 4 weeks.
-Has cancer or history of cancer (solid organ, hematologic including myelodysplastic syndrome or melanoma in situ) or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma, or carcinoma of cervix in situ that has been treated with no evidence of recurrence).
-Premalignant cervical or vulvar disease.
-Live vaccine administration within the last 4 weeks.
-The concomitant use of strong CYP3A4 enzyme inducers.
-Inadequate birth control (if pre-menopausal), pregnancy, planning pregnancy during the study period and/or breast-feeding.
-A past medical history of depression and/or suicidal ideation. If these are reported on screening questions, then the subject will undergo a Patient Health Questionnaire 8 items (PHQ-8) excluding those when the total score is >=15.
-Patients with severe renal/liver impairment or concurrent medications that would interact with the trial medications.
-Patients with active tuberculosis (TB), including any symptoms or signs, or imaging showing active TB, or latent TB determined by a positive IFN-gamma release assay and including current treatment for latent TB.
-Patients with other serious infections, defined by evidence of active infection or febrile illness within 7 days prior to day 1; a history of serious bacterial, fungal, or viral infection requiring hospitalization and/or intravenous antimicrobial intervention within 60 days prior to Day 1; any ongoing evidence of chronic, bacterial infection (e.g. chronic pyelonephritis, chronic osteomyelitis, chronic bronchiectasis); a history of prosthetic joint infection where the prosthesis was not removed; Active herpes simplex virus or herpes zoster infection at Day 1; positive test for hepatitis B virus (positive HBsAg, HBcAb); Evidence of, or test positive for, hepatitis C virus (HCV) at Screening (anti-HCVAb), positive for human immunodeficiency virus by antibody testing (HIV-1 and -2 Ab).
-Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the participant’s immune status (e.g. history of opportunistic infections [e.g. Pneumocystis jirovecii pneumonia, histoplasmosis, or coccidioidomycosis], history of splenectomy, primary immunodeficiency).
-Severe SARS-CoV-2 infection (e.g. worsened shortness of breath and pneumonia) within 4 weeks prior to Screening. Additionally, in the case of prior SARS-CoV-2 infection, symptoms must have completely resolved and based on Investigator assessment in consultation with the clinical trial physician, there are no sequelae that would place the participant at a higher risk of receiving investigational intervention.
-Any history of hypersensitivity to the active substance(s) or to any of the excipients of deucravacitinib or methotrexate.
-Participation in another trial that could affect the current study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Treatment allocation will be performed by a separate party. Investigators and participants will be blinded to the allocation. Container labels will use KIT numbers.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation sequence will be by a pre-generated permuted block size of 4, with a 1:1 ratio of allocation, using appropriate statistical software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A total of 116 participants will be recruited to provide 80% statistical power with two-sided 5% significance level to detect a standardized mean difference of 0.70 in the mean change of GELP scores from baseline to week 32 between Deucravacitinib and Methotrexate groups. Intention-to-treat (ITT) and per-protocol set (PPS) analyses will be performed. All statistical tests will be performed at 0.05 level of significance.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
116
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 24819 0
North Shore Private Hospital - St Leonards
Recruitment postcode(s) [1] 40468 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 312406 0
Commercial sector/Industry
Name [1] 312406 0
Bristol-Myers Squibb
Country [1] 312406 0
Australia
Primary sponsor type
Individual
Name
Dr Rebecca Bronwyn Saunderson
Address
North Shore Private Hospital
3 Westbourne Street, St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 315839 0
None
Name [1] 315839 0
Address [1] 315839 0
Country [1] 315839 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311755 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 311755 0
NSLHD Research Office, Level 13 Kolling Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065
Ethics committee country [1] 311755 0
Australia
Date submitted for ethics approval [1] 311755 0
Approval date [1] 311755 0
30/05/2023
Ethics approval number [1] 311755 0
2022/ETH02022

Summary
Brief summary
Vulvar lichen planus (VLP) is a chronic inflammatory dermatosis characterized by erythema, erosions and hyperkeratosis on the vulva with possible vaginal involvement. The condition is particularly difficult to treat and runs a chronic and progressive course, requiring long-term management and follow-up. The first-line treatment for VLP is potent topical corticosteroids. However, approximately 20-40% of patients require second-line treatment with systemic immunosuppression to control their disease.

Some of the systemic medications that have been used to treat VLP include prednisolone, methotrexate, mycophenolate mofetil, azathioprine, hydroxychloroquine and cyclosporine, with varying results. The best documented agent appears to be methotrexate, with authors reporting moderate efficacy and safety profile. However, these studies were either retrospective or small case series. Overall, there is a lack of high-quality evidence, such as randomized controlled trials (RCTs), to compare and guide second-line systemic treatments in VLP.

The pathogenesis of VLP is not completely understood, but there is evidence of involvement of tyrosine kinase 2 (TYK2) mediated pathway. One drug known to modulate the TYK-2 pathway is Deucravacitinib (BMS-986165), a novel, oral, selective TYK-2 inhibitor. It is being studied in patients with psoriasis, psoriatic arthritis, and systemic lupus erythematosus with promising results.

Given the lack of high-quality evidence to guide the use of second-line systemic treatments in VLP, the evidence of involvement of TYK2-mediated pathway, and that the best documented systemic agent in VLP to date is methotrexate, the aim of this study is to conduct a double-blinded RCT comparing the efficacy and safety of Deucravacitinib to that of Methotrexate, in patients with VLP who have failed first-line treatment with potent topical corticosteroids.

Hypothesis: Deucravacitinib will be superior to methotrexate in treating VLP patients who have failed topical therapy with potent corticosteroids.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122250 0
Dr Rebecca Bronwyn Saunderson
Address 122250 0
North Shore Private Hospital
3 Westbourne Street, St Leonards NSW 2065
Country 122250 0
Australia
Phone 122250 0
+61 2 9966 0625
Fax 122250 0
Email 122250 0
[email protected]
Contact person for public queries
Name 122251 0
Marlene Wijaya
Address 122251 0
Royal North Shore Hospital
Reserve Road, St Leonards NSW 2065
Country 122251 0
Australia
Phone 122251 0
+61 2 9926 7111
Fax 122251 0
Email 122251 0
[email protected]
Contact person for scientific queries
Name 122252 0
Rebecca Bronwyn Saunderson
Address 122252 0
North Shore Private Hospital
3 Westbourne Street, St Leonards NSW 2065
Country 122252 0
Australia
Phone 122252 0
+61 2 9966 0625
Fax 122252 0
Email 122252 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIThe efficacy and safety of deucravacitinib compared to methotrexate, in patients with vulvar lichen planus who have failed topical therapy with potent corticosteroids: a study protocol for a single-centre double-blinded randomised controlled trial2024https://doi.org/10.1186/s13063-024-08022-y
N.B. These documents automatically identified may not have been verified by the study sponsor.