Safety and Efficacy of TLL018 in Patients With Plaque Psoriasis

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 70 subjects with moderate to severe plaque psoriasis.

Detailed Description
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Successfully screened subjects will be randomized in a ratio of 2:2:2:1 and stratified to previous biologics use for psoriasis. After a 4-week screening period (day -28-0), subjects will be randomly assigned to treatment for 12 weeks. Clinical psoriasis area and severity index (PASI), Physician's Global Assessment (PGA), 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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A Phase Ⅰb, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of TLL-018 in Subjects With Moderate to Severe Plaque Psoriasis

Conditions
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Moderate to Severe Plaque Psoriasis

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 plaque psoriasis for at least 6 months prior to Baseline; Subjects with moderate to severe plaque psoriasis covering ≥10% BSA, with a PASI ≥12 and sPGA score ≥3 at Baseline; Able and willing to give written informed consent. Exclusion Criteria: Other types of psoriasis (such as erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, etc.); Current drug-induced psoriasis, e.g., a new onset of psoriasis or an exacerbation of psoriasis induced by beta blockers, calcium channel blockers, antimalarial drugs or lithium; 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: 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: 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, 2pieces, BID | Drug: TLL018 tablets<br>* Oral tablets administered at different doses BID daily for 12 weeks.<br>* Other names: TLL018 Placeboes;|
| Experimental: Cohort 3<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 4<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 12 | 
| adverse events (AEs) according to severity | Number of adverse events (AEs) according to severity | From day 1 to Weeks 12 | 
| blood pressure from baseline | Change of blood pressure from baseline | From day 1 to Weeks 12 | 
| pulse rate from baseline | Change of pulse rate from baseline | From day 1 to Weeks 12 | 
| respiratory rate from baseline | Change of respiratory rate from baseline | From day 1 to Weeks 12 | 
| temperature from baseline | Change of oral temperature from baseline | From day 1 to Weeks 12 | 
| clinical laboratory abnormalities compared to baseline | Number of participants with clinical laboratory abnormalities compared to baseline | From day 1 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 day 1 to Weeks 12 | 
| physical examination findings from baseline | Number of participants with changes in physical examination findings from baseline | From day 1 to Weeks 12 | 
| 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 12 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI score decreased from baseline at week 4 | The percentage of subjects whose PASI score decreased by at least 50%(PASI 50) 75%(PASI 75) 90%(PASI 90) and 100%(PASI 100) from baseline at week 4 when comparing TLL-018 with placebo | Baseline to Week 4 | 
| PASI score decreased from baseline at week 8 | The percentage of subjects whose PASI score decreased by at least 50%(PASI 50) 75%(PASI 75) 90%(PASI 90) and 100%(PASI 100) from baseline at week 8 when comparing TLL-018 with placebo | Baseline to Week 8 | 
| PASI score decreased from baseline at week 12 | The percentage of subjects whose PASI score decreased by at least 50%(PASI 50) 75%(PASI 75) 90%(PASI 90) and 100%(PASI 100) from baseline at week 12 when comparing TLL-018 with placebo | Baseline to Week 12 | 
| (sPGA) 0/1 response at week 4 | static Physician Global Assessment (sPGA) 0/1 response | Baseline to Weeks 4 | 
| (sPGA) 0/1 response at week 8 | static Physician Global Assessment (sPGA) 0/1 response | Baseline to Weeks 8 | 
| (sPGA) 0/1 response at week 12 | static Physician Global Assessment (sPGA) 0/1 response | Baseline to Weeks 12 |