ANZCTR - Registration

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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]

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

Condition category

Condition code

Skin

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]

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]

The difference in mean change of GELP scores from baseline (week 8) to week 32 between Deucravacitinib and Methotrexate groups

Timepoint [1]

Baseline (week 8 post-enrolment) to week 32 post-enrolment

Secondary outcome [1]

Mean change in Vulvar Quality of Life Index (VQLI) scores

Timepoint [1]

Weeks 8, 24, 32 post-enrolment

Secondary outcome [2]

Weekly use of topical corticosteroid, collected from participant diary, and the number of 30-gram tubes used.

Timepoint [2]

Throughout the study up to week 32 post-enrolment

Secondary outcome [3]

Mean change in General Health Questionnaire-28 (GHQ-28) scores

Timepoint [3]

Weeks 8, 24, 32 post-enrolment

Secondary outcome [4]

Mean change in Physician Global Assessment (PGA) scores

Timepoint [4]

Weeks 8, 24, 32 post-enrolment

Secondary outcome [5]

Mean change in Patient Global Assessment (PtGA) scores

Timepoint [5]

Weeks 8, 24, 32 post-enrolment

Secondary outcome [6]

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]

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?

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]

North Shore Private Hospital - St Leonards

Recruitment postcode(s) [1]

2065 - St Leonards

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Bristol-Myers Squibb

Address [1]

Level 2/4 Nexus Ct, Mulgrave VIC 3170

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern Sydney Local Health District Human Research Ethics Committee

Ethics committee address [1]

NSLHD Research Office, Level 13 Kolling Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

30/05/2023

Ethics approval number [1]

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

Dr Rebecca Bronwyn Saunderson

Address

North Shore Private Hospital
3 Westbourne Street, St Leonards NSW 2065

Country

Australia

Phone

+61 2 9966 0625

Fax

rbsaunderson@gmail.com

Contact person for public queries

Name

Marlene Wijaya

Address

Royal North Shore Hospital
Reserve Road, St Leonards NSW 2065

Country

Australia

Phone

+61 2 9926 7111

Fax

Marlene.Wijaya@health.nsw.gov.au

Contact person for scientific queries

Name

Rebecca Bronwyn Saunderson

Address

North Shore Private Hospital
3 Westbourne Street, St Leonards NSW 2065

Country

Australia

Phone

+61 2 9966 0625

Fax

rbsaunderson@gmail.com

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

Source	Title	Year of Publication	DOI
Dimensions AI	The 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 trial	2024	https://doi.org/10.1186/s13063-024-08022-y

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added automatically