The Efficacy and Safety of TLL018 in Moderate-to-severe Plaque Psoriasis

Study Overview
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Brief Summary
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This is a Phase 2, multicenter, randomized, double-blinded, parallel dose group, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of 3 doses of TLL018 as therapy in 120 participants with moderate-to-severe PP.

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Multicenter Phase 2 Study Evaluating the Efficacy and Safety of TLL018 in Participants With Moderate-to-severe Plaque Psoriasis

Conditions
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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: Are between the ages of 18 and 75 years, inclusive, at time of informed consent. Capable of giving informed consent and complying with study procedures. Willing and able to adhere to study restrictions. Laboratory and medical history parameters within the protocol defined ranges. Body mass index (BMI) of 18.0 to 35.0 kg/m2inclusive. Have had a diagnosis of moderate-to-severe PP for at least 6 months prior to Baseline. Participants with moderate-to-severe PP covering ≥10% body surface area (BSA), with a Psoriasis Area and Severity Index (PASI) ≥12 and a static Physician's Global Assessment (PGA) score ≥3 at Baseline. ... Exclusion Criteria: Pregnant or nursing women. History of chronic alcohol or drug abuse within 6 months prior to Screening as determined by the Investigator based on medical history and patient interview Current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, neurologic, or psychiatric disease. Current and/or recent history (<30 days prior to Screening and/or <45 days prior to randomization) of a clinically significant viral, bacterial, fungal, parasitic, or mycobacterial infection. Any history of malignancies, except for non-recurrent basal cell skin cancer, squamous cell skin cancer, and cervical cancer in situ that are considered to be cured. Tests positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Hepatitis B test result positive definition: 1) hepatitis B surface antigen (HBsAg) positive, or 2) Hepatitis B core antibody positive and hepatitis B virus deoxyribonucleic acid positive or beyond the upper limit of normal (ULN) value; positive hepatitis C virus result is defined as having a positive hepatitis C antibody test with a positive confirmatory hepatitis C polymerase chain reaction test. Recent exposure to active tuberculosis (TB). Current evidence of active TB or current evidence of latent TB. Participants with positive TB test (e.g., QuantiFERON) that have been treated for latent TB. Previous or current autoimmune diseases (e.g., RA, systemic lupus erythematosus, IBD, scleroderma, inflammatory myopathy, mixed connective tissue disease overlap syndrome, etc.). Note, psoriatic arthritis patients are allowed. Other types of psoriasis (such as erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, drug-induced psoriasis) ....

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>TLL018 tables, 10 mg 1piece,BID | Drug: TLL018 tablets<br>* oral tablets administered BID for 12weeks<br>* Other names: TLL018 Placeboes;|
| Experimental: Cohort 2<br>TLL018 tables, 20 mg 1piece,BID | Drug: TLL018 tablets<br>* oral tablets administered BID for 12weeks<br>* Other names: TLL018 Placeboes;|
| Experimental: Cohort 3<br>TLL018 tables, 40 mg 1piece,BID | Drug: TLL018 tablets<br>* oral tablets administered BID for 12weeks<br>* Other names: TLL018 Placeboes;|
| Placebo Comparator: Cohort 4<br>placebo, 1piece,BID | Drug: TLL018 tablets<br>* oral tablets administered BID for 12weeks<br>* Other names: TLL018 Placeboes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of participants achieving PASI-75 | A patient was a responser if a minimum 75% PASI improvement from Baseline was achieved including measure of the average redness (erythema), thickness (induration), and scaliness (scaling) In calculating the PASI, severity is determined by dividing the body into four regions: head (h), upper extremities (u), trunk (t), and lower extremities (l).Each of these areas is assessed separately for erythema, induration, and scaling, which are rated on a scale of 0 (none) to 4 (very severe). Extent of psoriatic involvement is graded as follows: 0 = no involvement = 1% to 9% = 10% to 29% = 30% to 49% = 50% to 69% = 70% to 89% = 90% to 100%. PASI = 0.1 (Eh + lh + Sh) Ah + 0.2 (Eu + lu + Su) Au + 0.3 (Et +lt + St) At + 0.4 (El +ll +Sl) Al | Week12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving PGA score of 0 or 1 | A patient was a responser if PGA score of 0 or 1 condition was reached, as listed: (0 Clear) No signs of psoriasis, but post-inflammatory discoloration may be present; (1 Almost clear): Only minimal plaque elevation, scaling, and erythema. | From week 4 to Weeks 12 | 
| Proportion of participants achieving PASI-75 (except Week 12) | A patient was a responser if a minimum 75% PASI improvement from Baseline was achieved including measure of the average redness (erythema), thickness (induration), and scaliness (scaling) In calculating the PASI, severity is determined by dividing the body into four regions: head (h), upper extremities (u), trunk (t), and lower extremities (l).Each of these areas is assessed separately for erythema, induration, and scaling, which are rated on a scale of 0 (none) to 4 (very severe). Extent of psoriatic involvement is graded as follows: 0 = no involvement = 1% to 9% = 10% to 29% = 30% to 49% = 50% to 69% = 70% to 89% = 90% to 100%. PASI = 0.1 (Eh + lh + Sh) Ah + 0.2 (Eu + lu + Su) Au + 0.3 (Et +lt + St) At + 0.4 (El +ll +Sl) Al | From week 4 to Weeks 12(except Week 12) | 
| Proportion of participants achieving PASI-90 | A patient was a responser if a minimum 90% PASI improvement from Baseline was achieved including measure of the average redness (erythema), thickness (induration), and scaliness (scaling) In calculating the PASI, severity is determined by dividing the body into four regions: head (h), upper extremities (u), trunk (t), and lower extremities (l).Each of these areas is assessed separately for erythema, induration, and scaling, which are rated on a scale of 0 (none) to 4 (very severe). Extent of psoriatic involvement is graded as follows: 0 = no involvement = 1% to 9% = 10% to 29% = 30% to 49% = 50% to 69% = 70% to 89% = 90% to 100%. PASI = 0.1 (Eh + lh + Sh) Ah + 0.2 (Eu + lu + Su) Au + 0.3 (Et +lt + St) At + 0.4 (El +ll +Sl) Al | From week 4 to Weeks 12 |