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

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

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.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 336
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2J 7E1
      • Dermatology Research Institute Inc.
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 0C6
      • Enverus Medical Research
    • Surrey, British Columbia, Canada, V3R 6A7
      • Dr Chih-ho Hong Medical Inc.
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Wiseman Dermatology Research
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K8
      • CCA Medical Research
    • Cobourg, Ontario, Canada, K9A 0Z4
      • Skin Health
    • London, Ontario, Canada, N6H 5L5
      • DermEffects
    • North York, Ontario, Canada, M2M 4J5
      • North York Research Inc.
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • The Centre for Dermatology
    • Richmond Hill, Ontario, Canada, L4C 9M7
      • York Dermatology
    • Toronto, Ontario, Canada, M4W 2N4
      • Research Toronto
    • Toronto, Ontario, Canada, M5A 3R6
      • AvantDerm
    • Toronto, Ontario, Canada, M3H 5Y8
      • Toronto Research Centre
    • Windsor, Ontario, Canada, N8W 1E6
      • XLR8 Clinical Research
  • Quebec
    • Laval, Quebec, Canada, H7N 6L2
      • Clinique D
• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100045
    • Beijing Children's Hospital, Capital Medical University
  • Beijing, China
    • Children's Hospital Capital Institute of Pediatrics
  • Changsha, China, 410013
    • The Third Xiangya Hospital of Central South University
  • Chongqing, China
    • First Affiliated Hospital of Chongqing Medical University
  • Chongqing, China
    • The Southwest Hospital of Amu
  • Chongqing, China
    • Chongqing Traditional Chinese Medicine Hospital
  • Hangzhou, China, 310014
    • Zhejiang Province People's Hospital
  • Shanghai, China
    • Huashan Hospital Affiliated to Fudan University
  • Shanghai, China
    • Dermatology hospital of Shanghai
  • Shenyang, China, 110001
    • The First Hospital of China Medical University
  • Anhui
    • Hefei, Anhui, China
      • The Second Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • First Affiliated Hospital of Anhui Medical University
  • Beiing
    • Beijing, Beiing, China, 100044
      • Peking University People's Hospital
  • Fujian
    • Fuzhou, Fujian, China
      • First Affiliated Hospital of Fujian Medical University
    • Xiamen, Fujian, China
      • Zhongshan Hospital, Fudan University(Xiamen Branch)
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • Dermatology Hospital of Southern Medical University
    • Guangzhou, Guangdong, China
      • Guangdong Province Traditional Chinese Medical Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Wuhan No.1 Hospital
  • Hunan
    • Changsha, Hunan, China
      • The Second Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Hospital for Skin Diseases, Chinese Academy of Medical Sciences
    • Nanjing, Jiangsu, China
      • Jiangsu Province People's Hospital
    • Wuxi, Jiangsu, China
      • Wuxi No.2 People's Hospital
    • Zhenjiang, Jiangsu, China
      • Affiliated Hospital of Jiangsu University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China
      • Jiangxi Provincial Hospital of Dermatology
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300120
      • Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • The Children's Hospital Affiliated to Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • The First People's Hospital of Hangzhou
    • Yiwu, Zhejiang, China
      • The Fourth Hospital Affiliated to Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects must be at least at ≥12 and ≤75 years of age and body weight ≥40 kg
2. Subject has a diagnosis of atopic dermatitis for at least 1 year.
3. Meets all of the following disease activity criteria: BSA ≥10% of AD involvement. EASI ≥16. IGA ≥3. WI-NRS ≥4
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.
5. Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period).

Exclusion Criteria:

1. 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.
2. Have received certain treatments that are contraindicated.
3. 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.
4. Other active non-AD inflammatory skin diseases or conditions affecting skin
5. 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).
6. Acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation.
7. 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.
8. Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
9. 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.
10. Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception.
11. Subject has a previously received systemic JAK inhibitors
12. Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Core Treatment Active Experimental: SHR0302 Dose#1; Drug: SHR0302 Oral tablets taken once daily (QD) for 16 weeks	Drug: Core Treatment Active Experimental: SHR0302 Dose#1; Drug: SHR0302 Oral tablets taken once daily (QD) for 16 weeks
Experimental: Core Treatment Active Experimental: SHR0302 Dose#2; Drug: SHR0302 Oral tablets taken once daily (QD) for 16 weeks	Drug: Core Treatment Active Experimental: SHR0302 Dose#2; Drug: SHR0302 Oral tablets taken once daily (QD) for 16 weeks
Placebo Comparator: Core Treatment Placebo Comparator: Placebo; Drug: Placebo Oral tablets taken once daily (QD) for 16 weeks	Drug: Core Treatment Placebo Comparator: Placebo; Drug: Placebo Oral tablets taken once daily (QD) for 16 weeks
Experimental: Extension Treatment Active Experimental: SHR0302 Dose#1; Drug: SHR0302 Oral tablets taken once daily (QD) for 36 weeks	Drug: Extension Treatment Active Experimental: SHR0302 Dose#1; Drug: SHR0302 Oral tablets taken once daily (QD) for 36 weeks
Experimental: Extension Treatment Active Experimental: SHR0302 Dose#2; Drug: SHR0302 Oral tablets taken once daily (QD) for 36 weeks	Drug: Extension Treatment Active Experimental: SHR0302 Dose#2; Drug: SHR0302 Oral tablets taken once daily (QD) for 36 weeks

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
NRS-4 at Week 24, 32, 40, 52 and 56	Proportion of subjects achieving an improvement of WI-NRS ≥4 from baseline at all scheduled visits during extension treatment phase.	All scheduled visits from Week 24 - 56
EASI 75 at Week 24, 32, 40, 52 and 56	Proportion of subjects achieving EASI 75 at all scheduled visits during extension treatment phase.	All scheduled visits from Week 16 24 - 56
IGA 0/1 at Week 24, 32, 40, 52 and 56	Proportion of subjects achieving IGA0/1 and a reduction from baseline of ≥2 points at all scheduled visits during extension treatment phase.	All scheduled visits from Week 24 - 56
EASI 50 and EASI 90 at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56	Proportion of subjects with ≥50% EASI improvement from baseline (EASI 50) at all scheduled visits.	Day 1 to Week 56
Change of EASI from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56	Change from baseline in the eczema area and severity index (EASI) total score at all scheduled visits. The EASI score ranges from 0.0 to 72.0, can be varied in increments of 0.1, Higher scores indicate greater severity.	Day 1 to Week 56
SCORAD 50, SCORAD 75 and SCORAD 90 at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56	SCORing Atopic Dermatitis (SCORAD). Score of 0-103. Higher scores mean more severe. Proportion of subjects achieving a ≥50%, 75% and 90% improvement in SCORAD (SCORAD 50, SCORAD 75 and SCORAD 90) from baseline at all scheduled visits.	Day 1 to Week 56
Change of SCORAD from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56	Change from baseline in SCORAD at all scheduled visits	Day 1 to Week 56
Change of BSA from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56	Change from baseline in body surface area (BSA) affected at all scheduled visits	Day 1 to Week 56
Change of IgE from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56	Change from baseline in the level of serum IgE in peripheral blood at all scheduled visits.	Day 1 to Week 56
Change of eosinophils from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56	Change from baseline in the level of serum eosinophils in peripheral blood at all scheduled visits.	Day 1 to Week 56
Change of dermatology life quality index (DLQI) or Children's DLQI (CDLQI) PROs from baseline at Week 4, 8, 12, 16, 24, 32, 40, 52 and 56	Change from baseline in dermatology life quality index (DLQI) or Children's DLQI (CDLQI) score at all scheduled visits. The DLQI CDLQI consists of questions concerning patients' perception of the impact of skin diseases on different aspects of their health-related quality of life over the last week. This is not a scale. There are no minimum or maximum values. The quality index just captures a subjects perception of the impact of skin disease on different aspects of their health-related quality of life over the last week.	Day 1 to Week 56
Change of Patient-Oriented Eczema Measure (POEM) from baseline at Week 4, 8, 12, 16, 24, 32, 40, 52 and 56	Change from baseline in Patient-Oriented Eczema Measure (POEM) at all scheduled visits. 7-item, patient-administered scale that assesses disease severity in children and adults. Subjects respond to questions about the frequency of 7 symptoms (itching, sleep disturbance, bleeding, weeping/oozing, cracking, flaking, and dryness/roughness) over the last week. Response categories include "No days," "1-2 days," "3-4 days," "5-6 days," and "Every day" with corresponding scores of 0, 1, 2, 3, and 4, respectively. Scores range from 0-28 with higher total scores indicating greater disease severity.	Day 1 to Week 56

Collaborators and Investigators

• Sponsor: Reistone Biopharma Company Limited

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Actual): August 12, 2022
• Study Completion (Actual): May 23, 2023

Study Registration Dates

• First Submitted: May 1, 2021
• First Submitted That Met QC Criteria: May 4, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: RSJ10333

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No