A Study to Evaluate Efficacy and Safety of HS-10374 for Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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This study has been designed to explore the clinical efficacy and safety of HS-10374 in the treatment of moderate to severe plaque psoriasis. Additionally, this study is to find the optimal dosing for the future clinical development of HS-10374.

Detailed Description
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This is a 12-week, multi-center, randomized, double blind, placebo-controlled, Phase 2 study. The study duration includes a 4-week screening period, a 12-week treatment period, and a 4-week follow-up period. All eligible subjects will be randomly assigned to 1 of 3 treatment arms (HS-10374 Dose 1, HS-10374 Dose 2, and placebo) in an equal ratio.

Official Title
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A Multi-Center, Randomized, Double Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of HS-10374 in Adult Subjects With Moderate To Severe Plaque Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: HS-10374 tablets 1mg
* Drug: HS-10374 tablets 5mg
* Drug: HS-10374-matched placebo tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between the ages of 18-70 years Diagnosis of plaque psoriasis for at least 6 months Eligible for phototherapy or systemic therapy Plaque covering ≥ 10% of BSA PASI ≥ 12, sPGA ≥3 Exclusion Criteria: Diagnosis of non-plaque psoriasis or drug-induced psoriasis Recent history of infection, history or risk of serious infection Any major illness or evidence of unstable condition of major organ systems including psychiatric disease Any condition possibly affecting the PK process of the study drug Evidence of other skin conditions that would interfere with the evaluation of psoriasis History of hypersensitivity to the ingredients of study drugs, history of anaphylaxis History of lack of response to any therapeutic agent targeted to IL-12, IL-17 or IL-23 at approved doses after at least 3 months of therapy Have received the prohibited treatment during the protocol required washout period Any significant laboratory or procedure abnormalities that might place the subject at unacceptable risk during this study period

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-10374 Dose 1<br> | Drug: HS-10374 tablets 1mg<br>* Administered orally QD for 12 weeks<br>Drug: HS-10374 tablets 5mg<br>* Administered orally QD for 12 weeks<br>Drug: HS-10374-matched placebo tablets<br>* Administered orally QD for 12 weeks<br>|
| Experimental: HS-10374 Dose 2<br> | Drug: HS-10374 tablets 1mg<br>* Administered orally QD for 12 weeks<br>Drug: HS-10374 tablets 5mg<br>* Administered orally QD for 12 weeks<br>|
| Active Comparator: Placebo<br> | Drug: HS-10374-matched placebo tablets<br>* Administered orally QD for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with moderate to severe plaque psoriasis achieving PASI 75 response at Week 12 | Psoriasis Area and Severity Index (PASI) is a scoring system quantifying the severity of psoriasis based on both lesion severity and area of involvement. PASI assessment is performed by investigators, and the numeric score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 response is defined as 75% or greater improvement in PASI score from baseline. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity and association with the study drug of adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation |  | Baseline to Week 16 | 
| Number of participants with clinical laboratory abnormalities | Clinical laboratory tests include hematology, coagulation testing, blood chemistry, urinalysis, stool analysis, high-sensitivity C-reactive protein, etc. | Baseline to Week 16 | 
| Number of participants with abnormalities of vital signs | Vital signs measured include blood pressure, pulse rate, and temperature. | Baseline to Week 16 | 
| Number of participants with abnormalities of physical examination | Physical examination includes assessments of general appearance, skin, lymph nodes, head, neck, lung, heart, abdomen, spine, extremities, nervous system, etc. | Baseline to Week 16 | 
| Incidence of clinically significant changes in electrocardiogram (ECG) | ECG parameters include heart rate, PR interval, RR interval, QRS duration, QTcF interval. | Baseline to Week 16 | 
| Proportion of patients with sPGA 0/1 at specified time points | Static physician's global assessment (sPGA) of psoriasis is an average assessment of all psoriatic lesions based on erythema, induration, and scale. It's a 5-point scale performed by investigators. A sPGA score of 0 or 1 means clear or almost clear respectively. | Baseline to Week 16 | 
| PASI 50 response rates at specified time points | Psoriasis Area and Severity Index (PASI) is a scoring system quantifying the severity of psoriasis based on both lesion severity and area of involvement. PASI assessment is performed by investigators, and the numeric score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 50 response is defined as 50% or greater improvement in PASI score from baseline. | Baseline to Week 16 | 
| PASI 75 response rates at specified time points | Psoriasis Area and Severity Index (PASI) is a scoring system quantifying the severity of psoriasis based on both lesion severity and area of involvement. PASI assessment is performed by investigators, and the numeric score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 response is defined as 75% or greater improvement in PASI score from baseline. | Baseline to Week 16 | 
| PASI 90 response rates at specified time points | Psoriasis Area and Severity Index (PASI) is a scoring system quantifying the severity of psoriasis based on both lesion severity and area of involvement. PASI assessment is performed by investigators, and the numeric score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 90 response is defined as 90% or greater improvement in PASI score from baseline. | Baseline to Week 16 | 
| PASI 100 response rates at specified time points | Psoriasis Area and Severity Index (PASI) is a scoring system quantifying the severity of psoriasis based on both lesion severity and area of involvement. PASI assessment is performed by investigators, and the numeric score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 100 response is defined as 100% improvement in PASI score from baseline. | Baseline to Week 16 | 
| Change from baseline in PASI scores at specified time points | Psoriasis Area and Severity Index (PASI) is a scoring system quantifying the severity of psoriasis based on both lesion severity and area of involvement. PASI assessment is performed by investigators, and the numeric score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity. | Baseline to Week 16 | 
| Change from baseline in BSA at specified time points | Psoriasis body surface area (BSA) involvement is measured using the handprint method with the size of a patient's handprint representing  1% of body surface area involved. | Baseline to Week 16 | 
| Change from baseline in DLQI scores at specified time points | The dermatology life quality index (DLQI) is a patient reported outcome measurement. It's a questionnaire consisting of 10 questions concerning patients' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week. Each question is scored on a scale of 0 to 3, and the sum of each scores range from 0 (no impairment of life quality) to 30 (maximum impairment). | Baseline to Week 16 | 
| Ctrough | Trough observed plasma concentration. | Baseline to Week 12 |