Ritlecitinib for Chronic Urticaria

Overseen By Giselle Singer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ahuva D Cices

Must be taking: H1-antihistamines

Must not be taking: JAK inhibitors, Glucocorticosteroids

Disqualifiers: Active infections, Cancer, HIV, 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

Compensation: Varies

Number of Visits: 9

Duration: 12 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking second-generation H1-antihistamines for your condition, you must continue the same dose throughout the trial. The protocol does not specify about other medications, so it's best to discuss your specific situation with the study team.

How does the drug Ritlecitinib differ from other treatments for chronic urticaria?

Ritlecitinib is unique because it targets specific pathways involved in inflammation, potentially offering a new approach for patients who do not respond to standard antihistamine treatments. Unlike traditional treatments, it may work by modulating the immune response, similar to other novel therapies like tofacitinib and remibrutinib, which also target specific enzymes involved in the inflammatory process. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this research study is to see if a drug called ritlecitinib is safe and effective for treating chronic spontaneous urticaria (CSU). CSU is hives and itching lasting over six weeks. Ritlecitinib is approved by the Food and Drug Administration (FDA) to treat another condition, but it is not approved for treating CSU. Participation is expected to last 20 weeks and include 7 clinic visits. This study will involve physical examinations, blood tests, looking at and taking pictures of participant's skin and hives, optional skin biopsies, and hearing tests. Eligible participants for this study will take ritlecitinib for 12 weeks and complete a daily diary about their skin and hives. The main risks of being in this study are side effects from ritlecitinib. Less than 1 in 10 people taking ritlecitinib experience diarrhea, acne, hives, rash, inflammation of hair follicles, dizziness, and increased blood levels of creatine phosphokinase (a muscle protein). Participants could also experience a rare but serious side effect, such as shingles, unusual infection, cancer, or blood clot. Benefits of participating in this study include a potential improvement in participant's condition and quality of life. Participating in this study may also help researchers develop new ways of helping future patients.

Research Team

Ahuva Cices, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for people with chronic spontaneous urticaria (CSU), which means they've had hives and itching for over six weeks. Participants will be involved in the study for 20 weeks, attending 7 clinic visits, undergoing physical exams, blood tests, skin assessments, optional biopsies, and hearing tests.

Inclusion Criteria

Participant has been informed about study procedures and medications and has provided informed consent prior to initiation of any study-specific activities/procedures

I can communicate well and follow study instructions.

Participant has a negative Tuberculin purified protein derivative (PPD) or QuantiFERON TBGold test (QFT) at screening or within the last 12 months

Exclusion Criteria

I have a history of TB that was not treated or not treated well, or I am currently being treated for active TB.

I am infected with Hepatitis B or C.

Prior treatment with other concomitant investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ritlecitinib for 12 weeks and complete a daily diary about their skin and hives

12 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Ritlecitinib

Trial Overview The trial is testing ritlecitinib's safety and effectiveness on CSU. Although not FDA-approved for CSU yet, it's being used to see if it can improve symptoms. Participants will take the drug for 12 weeks and keep a daily diary of their skin condition.

Participant Groups

Group I: persistent, progressive, or recurrent chronic spontaneous urticaria (CSU). Experimental Treatment 1 Intervention

Participants with persistent, progressive, or recurrent chronic spontaneous urticaria (CSU).

Who Is Running the Clinical Trial?

Ahuva D Cices

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

Tofacitinib, a JAK1/3 inhibitor, showed significant improvement in patients with refractory chronic urticaria (CU) and urticarial vasculitis (UV), even after they had not responded to other treatments.

The use of tofacitinib allowed for the tapering and discontinuation of other medications like cyclosporine and antihistamines, suggesting it may be an effective new treatment option for difficult-to-treat cases of CU and UV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of oral tofacitinib in refractory chronic spontaneous urticaria and urticarial vasculitis. Mansouri, P., Mozafari, N., Chalangari, R., et al.[2023]

In a phase 2b extension study involving 230 patients with chronic spontaneous urticaria (CSU), remibrutinib showed a favorable safety profile, with most adverse events being mild to moderate and not directly related to the treatment.

Remibrutinib provided significant and sustained efficacy, with 55.8% of patients achieving complete response (UAS7 = 0) and 68.0% achieving well-controlled disease (UAS7 ≤6) after 52 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. Jain, V., Giménez-Arnau, A., Hayama, K., et al.[2023]

In a study of 99 patients with severe chronic idiopathic urticaria, oral cyclosporin A (CsA) significantly reduced treatment failures compared to placebo, indicating its efficacy in managing this difficult condition.

CsA treatment led to notable improvements in symptom scores after 8 and 16 weeks, although two patients experienced hypertension, highlighting the need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclosporine in chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. Vena, GA., Cassano, N., Colombo, D., et al.[2022]

Dupilumab shows promise as a long-term treatment for chronic spontaneous urticaria, with 67% of patients maintaining remission after stopping the therapy for up to 22 months.

This case series, involving six patients who previously did not respond to antihistamines or high-dose omalizumab, suggests that dupilumab may have disease-modifying effects in managing chronic spontaneous urticaria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients treated with dupilumab for chronic spontaneous urticaria: A case report. Abadeh, A., Lee, JK.[2022]

In a study involving 134 patients with chronic idiopathic urticaria (CIU), the addition of theophylline to cetirizine significantly improved treatment effectiveness, with benefits observed after at least one month of treatment.

The combination therapy was well tolerated, showing no adverse effects, indicating that theophylline can be a safe and effective adjunct treatment for managing CIU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theophylline as 'add-on' therapy to cetirizine in patients with chronic idiopathic urticaria. A randomized, double-blind, placebo-controlled pilot study. Kalogeromitros, D., Kempuraj, D., Katsarou-Katsari, A., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of oral tofacitinib in refractory chronic spontaneous urticaria and urticarial vasculitis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Cyclosporine in chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients treated with dupilumab for chronic spontaneous urticaria: A case report. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Theophylline as 'add-on' therapy to cetirizine in patients with chronic idiopathic urticaria. A randomized, double-blind, placebo-controlled pilot study. [2013]