Efficacy and Safety of Baricitinib in Oral Lichen Planus: a Proof-of-Concept Study

Oral Lichen Planus Clinical Trial

Official title:

Efficacy and Safety of Baricitinib for the Treatment of Oral Lichen Planus: A Proof-of-Concept Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06158113
• Other study ID #: 22-0969
• Status: Recruiting
• Phase: Phase 2
• Start date: March 13, 2024
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: University of North Carolina, Chapel Hill
• Contact: Erika Hanami
• Phone: 984-974-3682
• Email: erika_hanami[@]med.unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lichen Planus
• Lichen Planus, Oral
• Oral Lichen Planus

Intervention

Drug:
• Baricitinib 4 milligram Oral Tablet
4 milligrams once daily

Locations

Country	Name	City	State
United States	UNC Dermatology and Skin Cancer Center	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Estimated response to 24 weeks of treatment with 4mg of baricitinib daily using the Investigator's Global Assessment (IGA).	The Investigator Global Assessment (IGA) represents the study doctor's overall assessment of the extent of disease. It assesses changes in symptomatic Oral Lichen Planus and it is meant to be a well-defined and reliable tool to measure disease severity in clinical studies. This tool assigns a score of 0-4 depending on how severe the disease is, with higher scores meaning worse disease. Overall change from baseline to week 24 reported.	Baseline, 24 weeks
Primary	Change in Oral Disease Severity Scale (ODSS) Scores	The Oral Disease Severity Scale (ODSS) is a validated tool to assess severity of Oral Lichen Planus. For scoring, the oral cavity is divided into 17 sites and assigned three different scores. A site score, which captures disease extent, a severity score, and an activity score which is obtained by multiplying the site and severity scores. Independently study participants are asked to fill in a numerical rating scale graded from 0-10, with zero meaning no pain and 10 being the worst imaginable pain felt within the last 4 weeks. Scores are added together and range from 0-106, with higher scores meaning more severe disease. Overall change from baseline to week 24 will be reported.	Baseline, 24 weeks
Secondary	Changes in Quality of Life as assessed with the Chronic Oral Mucosal Disease Questionnaire-26 (COMDQ-26).	The Chronic Oral Mucosal Disease Questionnaire-26 (COMDQ-26) is a 26-item validated survey specific to assess changes in quality of life in patients with Oral Lichen Planus. The total score of the COMDQ-26 ranges from 0-104 with higher scores indicating worse quality of life. The number of participants that achieve at least a 9 point reduction in their scores from baseline will be reported.	Baseline, 24 weeks