Efficacy and Safety Evaluation of Povorcitinib in Adult Patients with Chronic Spontaneous Urticaria: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study

Trial ID: 2022-503062-72-00
Protocol: INCB 54707-207
Sponsor: Incyte Corp.

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Diseases & Conditions

Chronic spontaneous urticaria

Objectives

The primary objective of this study is to evaluate the **efficacy** of **povorcitinib** in adult participants with **Chronic Spontaneous Urticaria (CSU)**. This is clinically relevant as CSU is a condition characterized by the spontaneous appearance of hives and/or angioedema without an identifiable trigger, significantly impacting patients' quality of life. Effective treatment options are essential for managing symptoms and improving patient outcomes.

Secondary objectives include further evaluation of the efficacy of povorcitinib in adult participants with CSU. This additional assessment aims to provide a more comprehensive understanding of the therapeutic potential of povorcitinib in this patient population.

Participants

The clinical trial involves a total of **70 participants** diagnosed with **Chronic Spontaneous Urticaria** (CSU). The study population comprises both male and female adults aged between 18 and 65 years. Participants were selected based on their diagnosis of CSU for at least three months prior to screening and their condition being refractory to second-generation H1 antihistamines. The trial includes individuals who are able to comprehend and willing to sign a written informed consent form, as well as those who can comply with the study protocol and procedures, including the completion of a daily electronic diary. Participants are also required to agree to use contraception as specified in the study protocol. The trial population includes a vulnerable group, indicating that special considerations are in place to ensure their safety and well-being throughout the study. Lifestyle factors such as diet and physical activity are not specified in the available data.

Plans and Procedures

The clinical trial is a **Phase 2**, double-blind, randomized, placebo-controlled study designed to evaluate the efficacy and safety of **povorcitinib** in adult participants with **chronic spontaneous urticaria**. The trial will involve a dose-ranging approach to determine the optimal dosage of povorcitinib. Participants will be randomly assigned to receive either povorcitinib or a matching placebo, administered orally in tablet form. The trial is expected to commence recruitment on December 1, 2023, and is estimated to conclude by July 11, 2025, with a maximum treatment period of 36 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, diagnosis, and refractoriness to second-generation H1 antihistamines. Following successful screening, participants will be enrolled and randomized into the treatment groups. The primary endpoint of the study is the change from baseline in the Urticaria Activity Score over 7 days (UAS7) at Week 12. Secondary endpoints include the proportion of participants achieving controlled disease (UAS7 ≤ 6) and those with UAS7 = 0 at Week 12.

Throughout the trial, participants will attend regular follow-up visits to monitor their response to treatment and any adverse events. These visits will include assessments of efficacy, safety, and compliance with the study protocol. The end-of-study visit will occur at the conclusion of the treatment period, where final evaluations will be conducted. Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including non-compliance with the study protocol or the occurrence of significant adverse events.

Treatment

The clinical trial involves the administration of **Povorcitinib**, an experimental medication, to evaluate its efficacy in adult participants with **Chronic Spontaneous Urticaria**. Povorcitinib is provided in the form of a **tablet** and is administered **orally**. The maximum daily dose of Povorcitinib is **75 mg**, with a total maximum dose of **18,900 mg** over a treatment period of up to **36 weeks**. The active substance, Povorcitinib, is of chemical origin and is developed by Incyte Corporation. The trial aims to assess the dose-ranging efficacy and safety of this medication.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, randomized, placebo-controlled study. The placebo is designed to match the appearance of the Povorcitinib tablet but does not contain the active substance. The use of a placebo allows for the assessment of the true efficacy of Povorcitinib by providing a control group for comparison. The placebo administration follows the same oral route and dosing schedule as the experimental medication to maintain the study's blinding integrity.

Efficacy

The efficacy of **povorcitinib** in the treatment of chronic spontaneous urticaria (CSU) will be assessed through a series of predefined endpoints in this Phase 2, double-blind, randomized, placebo-controlled, dose-ranging study. The primary endpoint for evaluating efficacy is the change from baseline in the Urticaria Activity Score over 7 days (UAS7) at Week 12. This score is calculated as the 7-day sum of the individual, daily recorded scores for Hives Severity Score (HSS) and Itch Severity Score (ISS).

Secondary endpoints include the proportion of participants who achieve a UAS7 score of 6 or less, indicating controlled disease, at Week 12, as well as the time to first achievement of a UAS7 score of 6 or less during the placebo-controlled period. Additionally, the proportion of participants with a UAS7 score of 0 at Week 12 will be evaluated. These efficacy parameters will be measured and collected at specified timepoints, with the primary analysis occurring at Week 12. The use of validated scales such as the UAS7 ensures the reliability and consistency of the efficacy assessments throughout the trial.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Ability to comprehend and willingness to sign a written ICF for the study.
Age 18 to 65 years inclusive at the time of signing the ICF.
CSU diagnosis for ≥ 3 months prior to screening.
CSU refractory to second-generation H1 antihistamines as defined in section 5.1, line 4 of the protocol.
Willingness and ability to comply with the study Protocol and procedures.
Willingness and ability to complete daily eDiary for the duration of the study.
Agreement to use contraception (as per section 5.1 of the protocol).

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Exclusion Criteria

Treatment with an anti-IgE biologic (eg, omalizumab) within 8 weeks prior to screening.
History of treatment failure with any systemic or topical JAK inhibitor (eg, abrocitinib, baricitinib, brepocitinib, cerdulatinib, delgocitinib, deucravacitinib, filgotinib, ivarmacitinib, pacritinib, ritlecitinib, ropsacitinib, ruxolitinib, tofacitinib, upadacitinib) for CSU or any other inflammatory condition.
Receipt of medical treatment or investigational drugs within the intervals (specified in section 5.2 of the protocol) before the baseline visit (Day 1).
Concurrent enrollment in another clinical study.
At the screening visit, any of the laboratory abnormalities defined in Table 6 of section 5.2 of the protocol.
Evidence of infection with Mycobacterium tuberculosis (ie, TB).
Active HIV or acquired immunodeficiency syndrome. Active HIV is defined as confirmed positive anti-HIV antibody test.
Evidence of HBV or HCV infection or risk of reactivation.
Known hypersensitivity or severe reaction to povorcitinib or excipients of povorcitinib and/or other products in the same class
Any condition, laboratory result, or result of screening assessments that would, in the investigator's and sponsor's (or designee's) judgment, interfere with full participation in the study, including administration of study drug and attending required study visits, pose a significant risk to the participant, or interfere with interpretation of study data.
Clearly defined predominant or sole trigger of chronic urticaria (chronic inducible urticaria) including urticaria factitial (symptomatic demographism), cold-, heat-, solar-, pressure-, delayed pressure–, aquagenic, cholinergic-, or contact-urticaria.
Other cutaneous or systemic diseases with symptoms of urticaria or angioedema.
Other skin or systemic diseases associated with chronic itching (eg, AD, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or psoriasis) that, in the investigator's opinion, might influence the study evaluations and results.
Women who are pregnant (or who are considering pregnancy) or breastfeeding.
Concurrent conditions or history of other diseases (as per section 5.2 of the protocol).
A screening 12-lead ECG that demonstrates clinically significant abnormalities requiring treatment (eg, acute MI, serious tachyarrhythmias or bradyarrhythmias) or that is indicative of serious underlying heart disease (eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, Wolff-Parkinson-White syndrome) or criteria associated with Q wave interval (QT)/Fridericia-corrected Q wave interval (QTcF) abnormalities.
Have undergone significant trauma or major surgery (per investigator's assessment) within 30 days preceding the screening visit.
History of clinically significant (per investigator's judgment) drug or alcohol abuse within 6 months preceding the screening visit.
Participants who have any form of dependence on the sponsor, investigator, or study site (including financial) and participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.