Povorcitinib for Chronic Spontaneous Urticaria

Recruiting at 50 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Incyte Corporation

Must be taking: Second-generation H1 antihistamines

Must not be taking: Anti-IgE biologics

Disqualifiers: Pregnancy, Thrombocytopenia, Malignancies, 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: Unknown

Duration: 12 weeks

136 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called povorcitinib for adults with a chronic skin condition called CSU. These patients haven't found relief with standard treatments. The medication works by reducing the body's overactive immune response.

Will I have to stop taking my current medications?

You will need to stay on a stable dose of your current second-generation H1 antihistamine throughout the study. The protocol does not specify about other medications, so it's best to discuss with the study team.

What data supports the effectiveness of the drug Povorcitinib for treating chronic spontaneous urticaria?

While there is no direct data on Povorcitinib for chronic spontaneous urticaria, similar treatments like tofacitinib, which also targets inflammatory pathways, have shown effectiveness in improving symptoms in patients with difficult-to-treat urticaria. This suggests that Povorcitinib might also be beneficial for this condition. ^{1 2 3 4 5}

How is the drug Povorcitinib different from other treatments for chronic spontaneous urticaria?

Povorcitinib is unique because it targets specific pathways involved in inflammation, potentially offering a new option for patients who do not respond to standard antihistamine treatments. While similar drugs like tofacitinib and remibrutinib also target inflammation, Povorcitinib's specific mechanism and effects in chronic spontaneous urticaria are still being explored. ^{1 2 3 4 6}

Eligibility Criteria

Adults with Chronic Spontaneous Urticaria (CSU) not responding well to standard antihistamines can join. They must have had CSU for at least 3 months, be on a stable dose of second-generation H1 antihistamine, and stick to their current treatment plan during the trial. People with other chronic itching diseases or who've used certain biologics recently can't participate.

Inclusion Criteria

My chronic hives don't improve with standard allergy pills.

I have been taking a consistent dose of a second-generation antihistamine and will continue to do so.

I have been diagnosed with chronic spontaneous urticaria for at least 3 months.

Exclusion Criteria

I have no cancer history, except for treated skin cancer or cervical pre-cancer.

My chronic hives have a known cause other than chronic spontaneous urticaria.

I am not pregnant, considering pregnancy, or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive placebo or povorcitinib for a 12-week period

12 weeks

Dose-Ranging Treatment

Participants are randomized to receive Dose A, B, or C of povorcitinib for an additional 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Povorcitinib

Trial Overview The trial is testing Povorcitinib's effectiveness and safety in adults whose CSU isn't controlled by usual treatments. Participants will either receive Povorcitinib or a placebo without knowing which one they're getting to compare results fairly.

Participant Groups

Group I: Povorcitinib Dose C Experimental Treatment 1 Intervention

Participants will receive dose C of povorcitinib for a 12 week period, followed by dose C for an additional 24 week period.

Group II: Povorcitinib Dose B Experimental Treatment 1 Intervention

Participants will receive dose B of povorcitinib for a 12 week period, followed by dose B for an additional 24 week period.

Group III: Povorcitinib Dose A Experimental Treatment 1 Intervention

Participants will receive dose A of povorcitinib for a 12 week period, followed by dose A for an additional 24 week period.

Group IV: Placebo followed by Povorcitinib Dose A, B, or C Experimental Treatment 2 Interventions

Participants will receive placebo for a 12 week period, followed by randomization to either Dose A, Dose B, or Dose C for an additional 24 week period.

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

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 study of 878 French patients with chronic urticaria, omalizumab (OMA) showed a longer drug survival rate compared to previous studies, with 50% of patients still on treatment 2.4 years after starting.

The main reason for discontinuing OMA was achieving well-controlled disease in 50% of patients, but many were able to restart treatment, indicating its effectiveness in managing chronic urticaria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. Litovsky, J., Hacard, F., Tétart, F., 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]

Recent advances in the classification and management of chronic urticaria emphasize the use of non-sedating H1-antihistamines, which can be administered in standard doses or increased up to four times if necessary, improving patient care.

For patients who do not respond to H1-antihistamines, omalizumab has been identified as a safe and effective treatment option, providing a new avenue for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights and advances in chronic urticaria: a Canadian perspective. Sussman, G., Hébert, J., Gulliver, W., et al.[2022]

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

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. [2023]

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

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

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

Similar Efficacy with Omalizumab in Chronic Idiopathic/Spontaneous Urticaria Despite Different Background Therapy. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Insights and advances in chronic urticaria: a Canadian perspective. [2022]

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

Fenebrutinib in H1 antihistamine-refractory chronic spontaneous urticaria: a randomized phase 2 trial. [2023]