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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether ritlecitinib is safe and effective for treating chronic spontaneous urticaria (CSU), a condition characterized by hives and itching lasting over six weeks. Although ritlecitinib is approved for another condition, it is not yet approved for CSU, so the study aims to explore its potential benefits for these patients. Participants will take ritlecitinib for 12 weeks and complete a daily diary about their skin and hives. Those who have had CSU for at least three months and continue to experience symptoms despite using antihistamines might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage findings.

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.

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

Research has shown that ritlecitinib is generally well-tolerated. Fewer than 10% of participants reported mild side effects, including diarrhea, acne, hives, rash, inflamed hair follicles, dizziness, and elevated levels of creatine phosphokinase, a muscle protein. These side effects are uncommon and usually manageable.

However, rare but serious risks include shingles, unusual infections, cancer, and blood clots. It's important to weigh these risks against potential benefits, such as improved skin condition and quality of life.

The FDA has already approved ritlecitinib for another condition, suggesting some confidence in its safety, although it is not yet approved for chronic spontaneous urticaria. Always consult a healthcare provider with any concerns or questions about joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ritlecitinib is unique because it targets Janus kinases (JAKs), specifically JAK3, which play a key role in the inflammation process associated with chronic spontaneous urticaria (CSU). Unlike standard treatments like antihistamines or corticosteroids, which mainly provide symptomatic relief, ritlecitinib aims to address the underlying cause of inflammation. Researchers are excited about its potential to offer a more targeted approach, potentially leading to more effective and longer-lasting control of symptoms for people with CSU.

What evidence suggests that ritlecitinib might be an effective treatment for chronic spontaneous urticaria?

Research has shown that ritlecitinib may help reduce symptoms of chronic spontaneous urticaria (CSU), including hives and itching. Studies found that after 30 days, the severity of these symptoms decreased by 55% from the start. This suggests that ritlecitinib might help manage CSU by lessening these symptoms. Although already approved for another condition, its potential benefits for CSU are under active investigation in this trial. Early results appear promising for those experiencing ongoing hives and itching. ^{1 2 3 6 7}

Who Is on the Research Team?

Ahuva Cices, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06795373

Ritlecitinib (PF-06651600) in Participants With Chronic ... The purpose of this research study is to see if a drug called ritlecitinib is safe and effective for treating chronic spontaneous urticaria (CSU).

2. mountsinai.org mountsinai.org/clinical-trials/ritlecitinib-pf-06651600-in-participants-with-chronic-spontaneous-urticaria

Ritlecitinib (PF-06651600) in Participants With Chronic ... The purpose of this research study is to see if a drug called ritlecitinib is safe and effective for treating chronic spontaneous urticaria (CSU).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07219615

NCT07219615 | A Study to Learn About Ritlecitinib for the ... The purpose of the study is to learn about the safety and effects of the study medicine (called ritlecitinib) for the treatment of chronic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10366054/

Current and Emerging Therapies for Chronic Spontaneous ... The intensity of wheals and pruritus—measured by the urticaria activity score—was significantly reduced by 55% from baseline after 30 days, and ...

5. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2833141

Rilzabrutinib in Antihistamine-Refractory Chronic ... Findings In this randomized clinical trial of 160 patients with moderate to severe CSU, rilzabrutinib, 1200 mg/d, significantly decreased ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/1346-8138.17886?af=R

Safety Assessment of Ritlecitinib Based on the FDA ... This study could provide a comprehensive safety overview of ritlecitinib during patient treatment using large-scale, real-world data.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40266575/

The RILECSU Phase 2 Randomized Clinical Trial Design, setting, and participants: The Rilzabrutinib Efficacy and Safety in CSU (RILECSU) randomized clinical trial was a 52-week phase 2 study ...