Baricitinib for Oral Lichen Planus

Overseen By Erika Hanami

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Systemic corticosteroids

Disqualifiers: Chronic liver disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests baricitinib, a medication that may help treat moderate to severe Oral Lichen Planus, a condition causing painful mouth sores. Researchers aim to evaluate baricitinib's effectiveness, its impact on quality of life, and potential side effects. Individuals struggling with Oral Lichen Planus who have not found success with other treatments might be suitable for this study. Participants will visit the study site monthly for eight months, take the medication at home, and complete questionnaires. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants must have failed at least one systemic therapy for Oral Lichen Planus and should follow appropriate washout for past medications. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants should have failed or not tolerated at least one non-corticosteroid systemic treatment for Oral Lichen Planus and that appropriate washout for past medications and stable doses for other medications should be followed as outlined in the protocol.

Is there any evidence suggesting that baricitinib is likely to be safe for humans?

Research has shown that baricitinib is generally safe for patients. Studies have found it effective in treating oral lichen planus, with no serious side effects reported. Although current trials focus on oral lichen planus, the FDA has already approved baricitinib for other uses, suggesting its likely safety. Participants taking baricitinib have experienced some mild side effects, such as headaches or minor infections, but these are common and manageable. Overall, the treatment appears safe based on available evidence. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Oral Lichen Planus?

Baricitinib is unique because it targets oral lichen planus with a novel approach. Unlike current treatments, which often involve corticosteroids or immunosuppressants to manage symptoms, baricitinib works as a Janus kinase (JAK) inhibitor. This means it blocks specific pathways involved in inflammation, potentially offering a more targeted and effective way to reduce symptoms. Researchers are excited because baricitinib's mechanism may provide relief with fewer side effects and better outcomes compared to traditional therapies.

What evidence suggests that baricitinib might be an effective treatment for Oral Lichen Planus?

Research has shown that baricitinib, the treatment under study in this trial, may help treat Oral Lichen Planus. In an earlier study, 83.3% of patients experienced significant improvement, with their condition improving by at least 50%. This indicates that many patients achieve strong results with baricitinib. The treatment also acted quickly, with benefits observed as early as week 16. These findings suggest that baricitinib could effectively manage this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Donna A Culton, MD, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

Adults with biopsy-proven moderate to severe Oral Lichen Planus who have not responded to at least one systemic treatment. Participants must use effective birth control, maintain oral hygiene, and be on stable doses of certain medications. Excluded are those with low blood counts, high cholesterol or triglycerides, poor liver or kidney function, serious infections or cancer history (with exceptions), risk of blood clots, recent dental procedures, hypersensitivity to JAK inhibitors.

Inclusion Criteria

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)

Must be able to comply with study instructions and attend all study visits

I have reviewed my vaccination status and will follow CDC guidelines for non-live vaccines before joining the study.

Exclusion Criteria

My liver isn't working well or I have a long-term liver problem.

I am allergic to JAK inhibitors.

Intention to breastfeed until 30 days after stopping investigational product

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4mg of baricitinib daily for up to 24 weeks to treat Oral Lichen Planus

24 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib

Trial Overview The trial is testing the effectiveness and safety of a drug called Baricitinib for treating Oral Lichen Planus. Patients will take the medication for six months and attend monthly visits where their disease severity and quality of life will be assessed through questionnaires.

How Is the Trial Designed?

Group I: Baricitinib Experimental Treatment 1 Intervention

Participants will be asked to take 4mg of baricitinib by mouth daily for up to 24 weeks.

Baricitinib is already approved in United States, European Union for the following indications:

Approved in United States as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Approved in European Union as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Janus kinase (JAK) inhibitors, such as upadacitinib, tofacitinib, and baricitinib, have shown promising safety and efficacy in treating various forms of lichen planus (LP), particularly lichen planopilaris, nail LP, and erosive LP, based on multiple case reports and series.

The INF-γ/CXCL10 signaling pathway is implicated in the chronic inflammation of LP, suggesting that targeting JAKs could be a beneficial therapeutic strategy, warranting further clinical trials to evaluate their effectiveness in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibitors in lichen planus: a review of pathogenesis and treatments. Motamed-Sanaye, A., Khazaee, YF., Shokrgozar, M., et al.[2022]

In a phase II study involving 12 patients, topical ruxolitinib significantly reduced the total lesion count in cutaneous lichen planus by a median of 50 lesions after 8 weeks of treatment, indicating its efficacy.

Transcriptomic analysis revealed that cutaneous lichen planus is driven by interferon pathways, and the treatment with ruxolitinib led to downregulation of interferon-stimulated genes, supporting its mechanism of action in targeting this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib Cream in the Treatment of Cutaneous Lichen Planus: A Prospective, Open-Label Study. Brumfiel, CM., Patel, MH., Severson, KJ., et al.[2022]

In a pooled analysis of two phase 3 trials involving 1200 adults with severe alopecia areata, increasing the dose of baricitinib from 2 mg to 4 mg led to significant improvements in hair regrowth, with 25.9% of previously non-responding patients achieving a SALT score of 20 or lower by week 76.

Clinician-reported outcomes for eyebrow and eyelash hair loss also improved, with response rates increasing from 19.3% to 37.9% for eyebrows and from 24.1% to 40.9% for eyelashes, demonstrating the efficacy of uptitration in enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes for Uptitration of Baricitinib Therapy in Patients With Severe Alopecia Areata: A Pooled Analysis of the BRAVE-AA1 and BRAVE-AA2 Trials. Ko, JM., Mayo, TT., Bergfeld, WF., et al.[2023]

Baricitinib (Olumiant®) has been shown to significantly improve scalp coverage in patients with alopecia areata, with a higher percentage achieving at least 80% coverage after 36 weeks of treatment compared to placebo in two phase-3 trials.

While generally effective, baricitinib can cause side effects such as acne and urinary tract infections, and it is important to follow the recommended dosage of 2 mg or 4 mg daily based on hair loss severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olumiant® (Baricitinib)-A Newly Approved Janus Kinase Inhibitor for the Treatment of Alopecia Areata. Gupta, AK., Wang, T., Vincent, K., et al.[2022]

Topical curcumin showed some effectiveness in reducing pain and symptoms of oral lichen planus (OLP), but its efficacy was similar to or less than that of topical corticosteroids, which remain the preferred treatment.

Oral curcumin did not demonstrate significant benefits over placebo in treating OLP, although some safety and potential benefits were noted in an observational study, indicating more research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin, a turmeric extract, for oral lichen planus: A systematic review. White, CM., Chamberlin, K., Eisenberg, E.[2019]

In a study of 14 oral lichen planus (LP) biopsy specimens compared to matched controls, there was a significant increase in the expression of key adhesion molecules, indicating a compensatory response by keratinocytes to resist damage and prevent ulceration.

The intense expression of integrins and basement membrane proteins suggests that these changes may aid in epithelial migration and wound repair, while also indicating recent remodeling of the epithelial structure in LP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered interface adhesion molecules in oral lichen planus. Ramirez-Amador, V., Dekker, NP., Lozada-Nur, F., et al.[2019]

In a study of 33 cases of oral lichen planus (OLP), most samples showed low expression of PD-L1 (66.6% negative), indicating a compromised PD-L1/PD-1 immune pathway, which may affect the disease's progression.

High expression of PD-L2 (96.9%) was found, suggesting a potential immune tolerance mechanism that could contribute to the chronic nature of OLP, along with a low cytotoxic immune response indicated by a reduced CD8:GrB ratio.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of PD-L1, PD-L2, PD-1 and cytotoxic immune response in oral lichen planus. Costa, NL., Gonçalves, JAM., de Lima, SLG., et al.[2023]

The study found that vascular endothelial growth factor (VEGF) levels were significantly higher in patients with oral lichen planus (OLP) compared to healthy controls, indicating a potential role in the disease's pathogenesis.

In atrophic/erosive OLP (A/ELP), there was a strong positive correlation between VEGF and matrix metalloproteinase-2 (MMP-2) in connective tissue, suggesting that these proteins may be involved in the malignant transformation of OLP lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of VEGF and MMP-2 levels in oral lichen planus: An in vivo immunohistochemical study. Hazzaa, HH., El Shiekh, MAM., Abdelgawad, N., et al.[2022]

A systematic review identified 11 clinical severity scoring systems for oral lichen planus that have been validated for reliability, with the Thongprasom score, Oral Disease Severity Score (ODSS), and REU scoring systems being the most commonly reported.

Despite the validation of these scoring systems for oral lichen planus, there is a significant gap in standardized scoring systems for extraoral mucosal lichen planus, highlighting the need for further development and testing in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease severity scoring systems in mucosal lichen planus: A systematic review. Unnikrishnan, SP., Rampersaud, E., Mcgee, A., et al.[2023]

Tacrolimus mouth rinse was found to be effective in reducing symptoms of erosive and ulcerative oral lichen planus (OLP), showing significant improvement in REU scores compared to dexamethasone after 4 weeks of treatment.

Although the overall effective rate was similar between tacrolimus and dexamethasone at 4 and 12 weeks, tacrolimus demonstrated quicker effects, suggesting it could be a valuable treatment option for OLP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A randomized single-blind controlled clinical trial of tacrolimus mouth rinse on erosive oral lichen planus]. Zuo, WX., Li, XY., Cai, GY., et al.[2019]

In a study of 110 patients with oral lichen planus (OLP) and 76 control subjects, daily systemic medication did not significantly increase the incidence of OLP lesions, suggesting that medication use is not a major contributing factor to the development of these lesions.

Lichenoid drug reactions (DILRs) were found to occur in a very low percentage of patients, with the erosive form of OLP being more common in non-medicated individuals, indicating that medication-related reactions are relatively rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of a possible association between oral lichen planus and drug intake. A controlled study. Hirota, SK., Moreno, RA., dos Santos, CH., et al.[2022]

The study analyzed 11 hospitals and included patients with oral lichen planus (OLP), finding that the average age of patients was 49.2 years, with a majority being women (61.4%).

Key risk factors for developing erosive/ulcerative OLP included older age, a disease duration of 12 months or more, dental calculus, hypertension, diabetes, and heart disease, indicating that these factors may help identify patients at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-center cross-sectional study of 1495 Chinese oral lichen planus patients. Liu, J., Xu, H., Tang, G., et al.[2023]

Topical tacrolimus was not found to be more effective or safer than topical corticosteroids for treating erosive oral lichen planus, based on a meta-analysis of 9 randomized controlled trials involving 476 patients.

No serious adverse events were reported with topical tacrolimus, suggesting it is safe for use, but the overall efficacy compared to corticosteroids remains inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Topical Tacrolimus for Erosive Oral Lichen Planus: A Meta-analysis. Guo, CL., Zhao, JZ., Zhang, J., et al.[2019]

In a Phase 3 trial with 329 patients suffering from moderate-to-severe atopic dermatitis, baricitinib (4-mg and 2-mg) combined with topical corticosteroids showed significant improvements in health-related quality of life (HRQoL) and work productivity starting as early as Week 2.

Baricitinib 4-mg maintained these improvements through Week 16, demonstrating its efficacy in reducing symptoms and enhancing overall treatment benefits compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. Wollenberg, A., Nakahara, T., Maari, C., et al.[2021]

In a study of 28 patients with oral lichen planus (OLP) and 10 control subjects, CD8+ T cells in OLP showed a significant increase in the expression of TGF-beta receptor I, indicating altered signaling pathways in these immune cells.

The expression of TGF-beta receptor II did not show an increase in OLP patients compared to controls, suggesting a specific dysregulation in TGF-beta signaling that may contribute to the chronic inflammation characteristic of OLP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression of TGF-beta receptors in CD8+ T cells of oral lichen planus]. Lei, L., Yu, M., Gao, XY., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06158113?term=AREA%5BConditionSearch%5D(%22Lichen%20Planus%22)&rank=5

Efficacy and Safety of Baricitinib in Oral Lichen Planus: a ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11735091/

Rapid response of lichen planus to baricitinib associated with ... The primary outcome of PGA scores 0 to 3 (with ≥ 50% score improvement) was achieved in 83.3% of patients. Rapid improvement with baricitinib ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38260663/

Oral Baricitinib in the Treatment of Cutaneous Lichen Planus Results: An early and sustained clinical response was seen with 83.3% of patients responsive at week 16. Our molecular data identified a unique, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05188521

Baricitinib (LY3009104) in the Treatment of Cutaneous ... This research study is evaluating the safety and efficacy of Baricitinib in treating Cutaneous Lichen Planus (LP).

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06158113/efficacy-and-safety-of-baricitinib-in-oral-lichen-planus-a-proof-of-concept-study

Efficacy and Safety of Baricitinib in Oral Lichen Planus Study Summary. The goal of this clinical trial is to learn the effects of baricitinib (the study drug) in patients with Oral Lichen Planus.

6. withpower.com withpower.com/trial/phase-2-oral-lichen-planus-2024-4b167

Baricitinib for Oral Lichen Planus The provided research does not contain specific safety data for Baricitinib (Olumiant, LY3009104) in the treatment of oral lichen planus. The studies focus on ...

7. mayo.edu mayo.edu/research/clinical-trials/cls-20525704

A Study to Evaluate Baricitinib (LY3009104) to Treat ... The purpose of this study is to evaluate the safety and efficacy of Baricitinib (LY3009104) in cutaneous LP as assessed by the change in Physician Global ...