A Phase 2a Study of TAS5315 in Patients With Chronic Spontaneous Urticaria

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of TAS5315 in chronic spontaneous urticaria patients with an inadequate response to H1-antihistamines

Detailed Description
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The main purpose of this study is to assess the efficacy of TAS5315 in chronic spontaneous urticaria patients with an inadequate response to H1-antihistamines compared with placebo as measured by the change from baseline in weekly Urticaria Activity Score (UAS7) at week 12

Official Title
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A Phase 2a, Randomized, Double-blind, Study of TAS5315 in Chronic Spontaneous Urticaria Patients With an Inadequate Response to H1-antihistamines

Conditions
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Chronic Spontaneous Urticaria

Intervention / Treatment
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* Drug: TAS5315 Dose 1
* Drug: TAS5315 Dose 2
* Drug: TAS5315 Dose 3
* Drug: TAS5315 Dose 4
* Drug: TAS5315 Dose 5
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Aged 18 to 75 years Diagnosis of chronic spontaneous urticaria (CSU) Presence of itch and hives for at least 6 consecutive weeks prior to screening in spite of use of non-sedating H1-antihistamines for CSU UAS7 score ≥ 16 and HSS7 score ≥ 8 during 7 days prior to study entry In-clinic UAS ≥ 4 on study entry Willing and able to complete and Participate Daily for the duration of the study Key Exclusion Criteria Diseases other than CSU with symptoms of urticaria or angioedema, including urticarial vasculitis, erythema multiforme, mastocytosis, or hereditary or acquired angioedema Atopic dermatitis, psoriasis, ichthyosis, or other skin disease associated with chronic itching Bleeding diathesis Uncontrolled hypertension disease states Treatment with omalizumab or other humanized anti-human IgE monoclonal antibody therapies used to treat CSU within 4 months prior to screening Nonresponse to omalizumab or other humanized anti-human IgE monoclonal antibody therapies Have been treated with other Bruton's Tyrosine Kinase inhibitors Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS5315 Dose 1<br> | Drug: TAS5315 Dose 1<br>* Treatment period: oral administration for 12 weeks, QD<br>|
| Experimental: TAS5315 Dose 2<br> | Drug: TAS5315 Dose 2<br>* Treatment period: oral administration for 12 weeks, QD<br>|
| Experimental: TAS5315 Dose 3<br> | Drug: TAS5315 Dose 3<br>* Treatment period: oral administration for 12 weeks, QD<br>|
| Experimental: AS5315 Dose 4<br> | Drug: TAS5315 Dose 4<br>* Treatment period: oral administration for 12 weeks, QD<br>|
| Experimental: TAS5315 Dose 5<br> | Drug: TAS5315 Dose 5<br>* Treatment period: oral administration for 12 weeks, QD<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Screening period: oral administration for 2 weeks, QD Treatment period: oral administration for 12 weeks, QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in weekly Urticaria Activity Score (UAS7) at week 12 | The UAS7 is the sum of the HSS7 score (weekly Hives Severity Sore) and the ISS7 score (weekly Itch Severity Score). The range of the UAS7 score is 0 - 42. (Zuberbier et al. 1995; Zuberbier et al., 2014) | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete absence of hives and itch (UAS7=0) |  | Over time from week 1 to week 12 | 
| Disease control (UAS7<=6) |  | Over time from week 1 to week 12 | 
| Mean change from baseline in weekly Angioedema Activity Score (AAS7) | The AAS is a validated tool to assess occurrence of episodes of angioedema. The AAS7 is a weekly AAS score (AAS7). Minimum and maximum possible AAS7 scores are 0-105. | Over time from week 1 to week 12 | 
| Mean change from baseline in Dermatology life quality index (DLQI) | DLQI is a 10-item dermatology-specific quality of life (QoL) measure. The range of the DLQI score is 0 - 30. | Over time from week 1 to week 12 | 
| Mean change from baseline in Urticaria control test (UCT) | UCT is 4-item measure, which assesses symptoms, quality of life, treatment effectiveness. The range of the UCT score is 0 - 16. | Over time from week 1 to week 12 | 
| Mean change from baseline in pharmacodynamics marker | Pharmacodynamics marker are IgG, IgM, IgA, IgE, CRP and D-dimer. | Over time from week 1to week 12 |