Evaluate Efficacy and Safety of Oral SHR0302 in Subjects Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study that will enroll approximately 330 subjects aged 12 to 75 years old with moderate to severe atopic dermatitis.

Detailed Description
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This study consists of a screening period followed by a placebo-controlled treatment period and then an extension treatment period and completed after a follow-up period after the completion of active treatment.

Official Title
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A Randomized, Double Blind and Placebo Controlled Phase 3 Study to Evaluate Efficacy and Safety of Oral SHR0302 in Subjects Aged 12 Years and Older With Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Core Treatment Active Experimental: SHR0302 Dose#1
* Drug: Core Treatment Active Experimental: SHR0302 Dose#2
* Drug: Core Treatment Placebo Comparator: Placebo
* Drug: Extension Treatment Active Experimental: SHR0302 Dose#1
* Drug: Extension Treatment Active Experimental: SHR0302 Dose#2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects must be at least at ≥12 and ≤75 years of age and body weight ≥40 kg Subject has a diagnosis of atopic dermatitis for at least 1 year. Meets all of the following disease activity criteria: BSA ≥10% of AD involvement. EASI ≥16. IGA ≥3. WI-NRS ≥4 Subject has a recent history (within 6 months before the screening visit) of inadequate response or inability to tolerate topical AD treatments (TCS or TCI) or who have required systemic treatments for control of their disease. Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period). Exclusion Criteria: Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, malignancies, current or history of certain infections, lymphoproliferative disorders and other medical conditions at the discretion of the investigator. Have received certain treatments that are contraindicated. Subject currently has been diagnosed and has active forms of other inflammatory skin disease (e.g., psoriasis, or lupus erythematosus) that would interfere with the evaluation of atopic dermatitis or response to treatment. Other active non-AD inflammatory skin diseases or conditions affecting skin Subject with active/severe concomitant disease (s)/symptom(s) that requires administering of systemic corticosteroids or otherwise interferes with study participation or requires active frequent monitoring (e.g., unstable chronic asthma). Acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation. Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, malignancies, current or history of certain infections, lymphoproliferative disorders and other medical conditions at the discretion of the investigator. Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study Subject has any malignancies or has a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ. Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception. Subject has a previously received systemic JAK inhibitors Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study

Ages Eligible for Study
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Minimum Age: 12 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: Core Treatment Active Experimental: SHR0302 Dose#1<br>Drug: SHR0302 Oral tablets taken once daily (QD) for 16 weeks | Drug: Core Treatment Active Experimental: SHR0302 Dose#1<br>* Drug: SHR0302 Oral tablets taken once daily (QD) for 16 weeks<br>|
| Experimental: Core Treatment Active Experimental: SHR0302 Dose#2<br>Drug: SHR0302 Oral tablets taken once daily (QD) for 16 weeks | Drug: Core Treatment Active Experimental: SHR0302 Dose#2<br>* Drug: SHR0302 Oral tablets taken once daily (QD) for 16 weeks<br>|
| Placebo Comparator: Core Treatment Placebo Comparator: Placebo<br>Drug: Placebo Oral tablets taken once daily (QD) for 16 weeks | Drug: Core Treatment Placebo Comparator: Placebo<br>* Drug: Placebo Oral tablets taken once daily (QD) for 16 weeks<br>|
| Experimental: Extension Treatment Active Experimental: SHR0302 Dose#1<br>Drug: SHR0302 Oral tablets taken once daily (QD) for 36 weeks | Drug: Extension Treatment Active Experimental: SHR0302 Dose#1<br>* Drug: SHR0302 Oral tablets taken once daily (QD) for 36 weeks<br>|
| Experimental: Extension Treatment Active Experimental: SHR0302 Dose#2<br>Drug: SHR0302 Oral tablets taken once daily (QD) for 36 weeks | Drug: Extension Treatment Active Experimental: SHR0302 Dose#2<br>* Drug: SHR0302 Oral tablets taken once daily (QD) for 36 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator's Global Assessment (IGA) score of 0/1 at Week 16 | Proportion of subjects achieving Investigator's Global Assessment (IGA) score of clear (0) or almost clear (1) and a reduction from baseline of ≥2 points at Week 16. | 16 Weeks | 
| Eczema Area and Severity Index (EASI 75) at Week 16 | Proportion of subjects achieving at least a 75% improvement in Eczema Area and Severity Index (EASI 75) from baseline at Week 16. | 16 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worst-Itch Numeric Rating Scale (WI-NRS-4)-4 at Week 16 | Proportion of subjects achieving an improvement of Worst-Itch Numeric Rating Scale (WI-NRS) ≥4 from baseline at Week 16 | Week 16 | 
| Worst-Itch Numeric Rating Scale (WI-NRS) at Week 1, 4, 8 and 12 | Proportion of subjects achieving an improvement of WI-NRS ≥4 from baseline at all scheduled visits during placebo-controlled treatment phase other than Week 16. | Week 1, 4, 8 and 12 | 
| Time to WI-NRS response | Time from baseline to achieve at least 4 points improvement of WI-NRS during placebo-controlled treatment phase. | Baseline to Week 16 | 
| EASI 75 at Week 1, 4, 8 and 12 | Proportion of subjects achieving EASI 75 at all scheduled visits during placebo-controlled treatment phase except Week 16. | Week 1, 4, 8 and 12 | 
| IGA 0/1 at Week 1, 4, 8 and 12 | Proportion of subjects achieving IGA0/1 and a reduction from baseline of ≥2 points at all scheduled visits during placebo-controlled treatment phase except Week 16. | Week 1, 4, 8 and 12 |