Safety and Efficacy of TLL018 in Patients With Chronic Spontaneous Urticaria.

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled, multicenter clinical trial of about 36 subjects with moderate to severe Chronic Spontaneous Urticaria.

Detailed Description
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Successfully screened subjects will be randomized in a ratio of 1：1：1. After a 4-week screening period (day -28-0), subjects will be randomly assigned to treatment for 12 weeks. Clinical Urticaria Activity Score (UAS), dermatological Quality of Life Index (DLQI), physical exams and Laboratory tests will be performed at baseline, the end of weeks 4, 8 and 12 respectively.

Official Title
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Safety and Efficacy of TLL018 in Patients With Chronic Spontaneous Urticaria.

Conditions
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Chronic Spontaneous Urticaria

Intervention / Treatment
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* Drug: TLL018 tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had a diagnosis of moderate to severe Chronic Spontaneous Urticaria for at least 6 months prior to Baseline; Subjects with moderate to severe Chronic Spontaneous Urticaria UAS7 score ≥16 at Baseline; Able and willing to give written informed consent. Exclusion Criteria: Other types of Chronic Urticaria (such as Artificial urticaria, cold-contact urticaria, heat-contact urticaria etc); Other disease with symptoms of urticaria or angioedema, e.g., Urticaria vasculitis, color Vegetarian urticaria, erythema multiforme; History or symptoms of malignancy in any organ system regardless of treatment, and regardless of evidence of recurrence or metastasis; Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject's participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>TLL018 tablets 1piece,BID | Drug: TLL018 tablets<br>* Oral tablets administered at different doses BID daily for 12 weeks.<br>* Other names: TLL018 Placeboes;|
| Experimental: Cohort 2<br>TLL018 tablets 3pieces, BID | Drug: TLL018 tablets<br>* Oral tablets administered at different doses BID daily for 12 weeks.<br>* Other names: TLL018 Placeboes;|
| Placebo Comparator: Cohort 3<br>TLL018 placeboes 3pieces, BID | Drug: TLL018 tablets<br>* Oral tablets administered at different doses BID daily for 12 weeks.<br>* Other names: TLL018 Placeboes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment-emergent adverse events (AEs), serious adverse events (SAEs) and discontinuation due to AEs/SAEs | Number of participants with treatment-emergent adverse events (AEs), serious adverse events (SAEs) and discontinuation due to AEs/SAEs | From day 1 to Weeks 4 | 
| adverse events (AEs) according to severity | Number of adverse events (AEs) according to severity | From day 1 to Weeks 4 | 
| blood pressure from baseline | Change of blood pressure from baseline | From day 1 to Weeks 4 | 
| pulse rate from baseline | Change of pulse rate from baseline | From day 1 to Weeks 4 | 
| respiratory rate from baseline | Change of respiratory rate from baseline | From day 1 to Weeks 4 | 
| temperature from baseline | Change of oral temperature from baseline | From day 1 to Weeks 4 | 
| clinical laboratory abnormalities compared to baseline | Number of participants with clinical laboratory abnormalities compared to baseline | From day 1 to Weeks 4 | 
| ECG parameters from baseline | Change in 12-lead electrocardiogram (ECG) parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) from baseline | From day 1 to Weeks 4 | 
| physical examination findings from baseline | Number of participants with changes in physical examination findings from baseline | From day 1 to Weeks 4 | 
| Cmax of TLL018 | Maximum observed plasma concentration (Cmax) of TLL018 | 0 hour (pre-dose - within 30 minutes prior to dosing), and at 0.5, 1, 2, 4 and 8 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment-emergent adverse events (AEs), serious adverse events (SAEs) and discontinuation due to AEs/SAEs | Number of participants with treatment-emergent adverse events (AEs), serious adverse events (SAEs) and discontinuation due to AEs/SAEs | From week 4 to Weeks 12 | 
| adverse events (AEs) according to severity | Number of adverse events (AEs) according to severity | From week 4 to Weeks 12 | 
| blood pressure from baseline | Change of blood pressure from baseline | From week 4 to Weeks 12 | 
| pulse rate from baseline | Change of pulse rate from baseline | From week 4 to Weeks 12 | 
| respiratory rate from baseline | Change of respiratory rate from baseline | From week 4 to Weeks 12 | 
| temperature from baseline | Change of oral temperature from baseline | From week 4 to Weeks 12 | 
| clinical laboratory abnormalities compared to baseline | Number of participants with clinical laboratory abnormalities compared to baseline | From week 4 to Weeks 12 | 
| ECG parameters from baseline | Change in 12-lead electrocardiogram (ECG) parameters (PR Interval, QRS Complex, QT Interval, QTC Interval) from baseline | From week 4 to Weeks 12 | 
| physical examination findings from baseline | Number of participants with changes in physical examination findings from baseline | From week 4 to Weeks 12 | 
| UAS7 score decreased from baseline at week 4 | Change in mean value of UAS7 score from baseline at week 4 when comparing TLL-018 with placebo | Baseline to Week 4 | 
| UAS7 score decreased from baseline at week 8 | Change in mean value of UAS7 score from baseline at week 8 when comparing TLL-018 with placebo | Time Frame: Baseline to Week 8 | 
| UAS7 score decreased from baseline at week 12 | Change in mean value of UAS7 score from baseline at week 12 when comparing TLL-018 with placebo | Baseline to Week 12 | 
| DLQI score decreased from baseline at week 4 | Change in mean value of DLQI score from baseline at week 4 when comparing TLL-018 with placebo | Baseline to Weeks 4 | 
| DLQI score decreased from baseline at week 8 | Change in mean value of DLQI score from baseline at week 8 when comparing TLL-018 with placebo | Baseline to Weeks 8 | 
| DLQI score decreased from baseline at week 12 | Change in mean value of DLQI score from baseline at week 12 when comparing TLL-018 with placebo | Baseline to Weeks 12 |