Study Evaluating the Efficacy and Safety of Povorcitinib in Adults With Chronic Spontaneous Urticaria

Study Overview
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Brief Summary
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This study is being conducted to evaluate the efficacy and safety of povorcitinib in adults with CSU that is inadequately controlled using SOC treatments.

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging, Efficacy, and Safety Study of Povorcitinib in Participants With Chronic Spontaneous Urticaria

Conditions
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Chronic Idiopathic Urticaria, Hives, Angioedema, Pruritis, Urticaria, Chronic Spontaneous Urticaria

Intervention / Treatment
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* Drug: Povorcitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: CSU diagnosis for ≥ 3 months prior to screening. CSU refractory to second-generation H1 antihistamines Participants must have been on a stable dose of second-generation H1 antihistamine, and must agree to maintain the stable dose of second-generation H1 antihistamine throughout study. Willingness and ability to comply with the study Protocol and procedures. Further inclusion criteria apply Exclusion Criteria: Treatment with an anti-IgE biologic (eg, omalizumab) within 8 weeks prior to screening. Clearly defined underlying etiology for chronic urticarias other than CSU Other cutaneous or systemic diseases with chronic itching or with symptoms of urticaria or angioedema. Women who are pregnant (or who are considering pregnancy) or breastfeeding. Concurrent or history of Thrombocytopenia, coagulopathy, or platelet dysfunction, Venous and arterial thrombosis, deep vein thrombosis, pulmonary embolism, stroke, moderate to severe heart failure (NYHA Class III or IV), cerebrovascular accident, MI, coronary stenting, or CABG surgery, other significant cardiovascular diseases or uncontrolled hypertension Recipient of an organ transplant that requires continued immunosuppression. Any malignancies or history of malignancies with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ. Chronic or recurrent infectious disease. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Povorcitinib Dose A<br>Participants will receive dose A of povorcitinib for a 12 week period, followed by dose A for an additional 24 week period. | Drug: Povorcitinib<br>* oral; tablet<br>|
| Experimental: Povorcitinib Dose B<br>Participants will receive dose B of povorcitinib for a 12 week period, followed by dose B for an additional 24 week period. | Drug: Povorcitinib<br>* oral; tablet<br>|
| Experimental: Povorcitinib Dose C<br>Participants will receive dose C of povorcitinib for a 12 week period, followed by dose C for an additional 24 week period. | Drug: Povorcitinib<br>* oral; tablet<br>|
| Experimental: Placebo followed by Povorcitinib Dose A, B, or C<br>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. | Drug: Povorcitinib<br>* oral; tablet<br>Drug: Placebo<br>* oral; tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the urticaria activity score (UAS7) | Defined as the 7-day sum of the individual, daily recorded scores for HSS and ISS, at week 12. UAS scores range from 0-42; with higher scores reflecting greater disease activity. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who achieve UAS7 ≤ 6 (controlled disease) at Week 12 | Defined as the 7-day sum of the individual, daily recorded scores for HSS and ISS, at week 12. UAS scores range from 0-42; with higher scores reflecting greater disease activity. | 12 Weeks | 
| Time to first achievement of UAS7 ≤ 6 (controlled disease) during the PC period | Defined as the 7-day sum of the individual, daily recorded scores for HSS and ISS. UAS scores range from 0-42; with higher scores reflecting greater disease activity. | 12 Weeks | 
| Proportion of participants with UAS7 = 0 at Week 12. | Defined as the 7-day sum of the individual, daily recorded scores for HSS and ISS, at week 12. UAS scores range from 0-42; with higher scores reflecting greater disease activity. | 12 Weeks |