Clinical trial NCT06158113: Efficacy and Safety of Baricitinib in Oral Lichen Planus: a Proof-of-Concept Study
Official title: Efficacy and Safety of Baricitinib for the Treatment of Oral Lichen Planus: A Proof-of-Concept Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lichen Planus, Oral
Lichen Planus, Mucosal
Oral Lichen Planus
Keywords: Jak inhibitor
Janus kinase inhibitor
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2023-12-06
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn the effects of baricitinib (the study drug) in patients with Oral Lichen Planus. The main questions it aims to answer are:

* What is the efficacy of baricitinib in treating moderate to severe Oral Lichen Planus?
* Can baricitinib treatment in Oral Lichen Planus change quality of life?
* What side effects do patients with Oral Lichen Planus experience when treated with baricitinib?

Participants will be required to come in to monthly visits for up to eight months. During visits, participants will be:

* Evaluated for the extent of their disease
* Asked to fill out a questionnaire about their quality of life
* Given baricitinib for them to take at home for six months
* Evaluated for any potential side experienced while on treatment
* Asked to return 1 month after completing treatment


Eligibility criteria: Inclusion Criteria:

1. Voluntarily signed an Institutional Review Board (IRB) approved informed consent.
2. Be at least ≥ 18 years old.
3. Biopsy proven Oral Lichen Planus (OLP)
4. OLP patients with moderate to severe OLP, and must have failed or not tolerated at least one non-corticosteroid systemic treatment for OLP (such as metronidazole, hydroxychloroquine, methotrexate, mycophenolate mofetil, azathioprine, acitretin, rituximab, thalidomide, cyclosporine, apremilast, dapsone or systemic calcineurin inhibitor).
5. Subjects should practice daily oral hygiene (defined as brushing teeth twice daily) and be willing to maintain their routine oral hygiene procedure during study participation.
6. Willingness to abstain from certain mouth products during the course of the study
7. Must be willing to not receive any live vaccines during and up to 30 days after the end of treatment.
8. Vaccination status of subjects should be reviewed prior to study entry. Subjects must be encouraged to receive non-live vaccines following centers of disease control (CDC) guidelines for vaccination of those ≥18 years of age to prevent infectious disease 30 days before baseline.
9. Individuals who can potentially become pregnant must have a negative urine pregnancy test at screening and must be confirmed negative at time of enrollment (baseline visit).
10. Individuals who can potentially become pregnant must agree to use a highly effective form of birth control when engaging in sexual intercourse with a male partner during the study and for 30 days after the last dose.
11. Male subjects must be willing to use a highly effective method of contraception or practice true abstinence from sexual intercourse during the study and for 30 days after the last dose.
12. Must be able to comply with study instructions and attend all study visits.

Exclusion Criteria:

1. Absolute lymphocyte count \<750cells/mm\^3 within 30 days of starting study drug
2. Absolute neutrophil count \<1200cells/mm\^3 within 30 days of starting study drug
3. Hemoglobin \<10.0g/dL within 30 days of starting study drug
4. Platelet count \<100,000 cells/mm\^3 within 30 days of starting study drug
5. Fasting cholesterol levels \>400mg/dL or \>10.34mmol/L within 30 days of starting study drug or levels that may have required hospitalization, caused pancreatitis, or became life threatening.
6. Serum triglycerides \>500mg/dL or \>5.7mmol/L within 30 days of starting study drug.
7. Chronic liver disease with severe hepatic impairment as defined in the protocol.
8. Inadequate renal function tests defined as an estimated glomerular filtration rate (eGFR) based on the most recent available creatinine using the chronic kidney disease epidemiology collaboration equation (CKD-EPI) creatinine 2009 equation of \<60 millimeters/minute/1.73 meters squared (m\^2) within 30 days of starting study drug.
9. Ongoing active or recent clinically serious fungal, bacterial, viral, or parasitic infection.
10. History of gastrointestinal perforation
11. History of heart attack or significant cardiovascular risk that in the investigator's judgement, the risks of the subject participating in the study is greater than its benefit.
12. Hypercoagulable state such as history of deep vein thromboembolism (VTE) or stroke OR are considered at high risk of VTE.
13. History of cancer (except treated cutaneous basal cell carcinoma (BCC), cutaneous squamous cell carcinoma in situ (cSCCis) and in situ cervical cancer) unless it can be documented that the patient has been in a disease-free state for at least 5 years for high grade cancers with the following exception:

    * In case of clinical suspicion of malignancy in the oral cavity, a patient can only be included after an excluding biopsy
    * Any history of squamous cell carcinoma or melanoma (even if resected) in the mouth, as well as history of other non-squamous cell carcinoma (e.g., sarcoma, salivary gland tumors) in the mouth are excluded.
14. Subjects who may have signs of lymphoproliferative disease, such as lymphadenopathy or splenomegaly unless stable for the last 5 years
15. Professional dental cleaning within 2 weeks prior to baseline
16. Patient with any un-healed oral surgery (including recent diagnostic biopsies, if applicable) or oral laser therapeutic wound(s) at baseline visit
17. Subjects must have failed at least one systemic therapy for OLP to be included in the study. Appropriate washout for past medications received and stable doses for other medications should be followed as outlined in the protocol.
18. Hypersensitivity to Janus kinase (JAK) inhibitors.
19. Subjects with any serious concomitant illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma)
20. Subjects who require major surgery within 8 weeks of baseline and/or during the study are excluded.
21. Current participation in another clinical study and/or having received treatment with any non-marketed / investigational medicinal product (drug substance or medical device) within 30 days prior to baseline or 5.5 half-lives, whichever is longer.
22. Intention to become pregnant during the study period (30 days after stopping investigational product)
23. Intention to breastfeed until 30 days after stopping investigational product.
24. Any other condition that in the investigator's judgement the subject's risks are greater than the benefit from participating in the study or may interfere with interpretation of data.

Primary outcomes:
measure: Change in Oral Disease Severity Scale (ODSS) Scores
timeFrame: Baseline, 24 weeks
Secondary outcomes:
measure: Changes in Quality of Life as assessed with the Chronic Oral Mucosal Disease Questionnaire-26 (COMDQ-26).
timeFrame: Baseline, 24 weeks
Other outcomes:
measure: Estimated response to 24 weeks of treatment with 4mg of baricitinib daily using the Investigator's Global Assessment (IGA).
timeFrame: Baseline, 24 weeks
Locations:
city: Chapel Hill
country: United States
facility: UNC Dermatology and Skin Cancer Center
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Donna Culton, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Escudier M, Ahmed N, Shirlaw P, Setterfield J, Tappuni A, Black MM, Challacombe SJ. A scoring system for mucosal disease severity with special reference to oral lichen planus. Br J Dermatol. 2007 Oct;157(4):765-70. doi: 10.1111/j.1365-2133.2007.08106.x. Epub 2007 Aug 17.
citation: Wiriyakijja P, Porter S, Fedele S, Hodgson T, McMillan R, Shephard M, Ni Riordain R. Meaningful improvement thresholds in measures of pain and quality of life in oral lichen planus. Oral Dis. 2020 Oct;26(7):1464-1473. doi: 10.1111/odi.13379. Epub 2020 May 26.
citation: Damsky W, Wang A, Olamiju B, Peterson D, Galan A, King B. Treatment of severe lichen planus with the JAK inhibitor tofacitinib. J Allergy Clin Immunol. 2020 Jun;145(6):1708-1710.e2. doi: 10.1016/j.jaci.2020.01.031. Epub 2020 Feb 1. No abstract available.
citation: Shao S, Tsoi LC, Sarkar MK, Xing X, Xue K, Uppala R, Berthier CC, Zeng C, Patrick M, Billi AC, Fullmer J, Beamer MA, Perez-White B, Getsios S, Schuler A, Voorhees JJ, Choi S, Harms P, Kahlenberg JM, Gudjonsson JE. IFN-gamma enhances cell-mediated cytotoxicity against keratinocytes via JAK2/STAT1 in lichen planus. Sci Transl Med. 2019 Sep 25;11(511):eaav7561. doi: 10.1126/scitranslmed.aav7561.