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

• Sponsor: Reistone Biopharma Company Limited (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04875169
• Collaborator: (none)
• Enrollment: 330
• Locations: 44
• Arms: 5
• Anticipated Duration (Months): 26
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	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	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 330 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 30, 2021
• Anticipated Primary Completion Date: Jun 30, 2023
• Anticipated Study Completion Date: Jun 30, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Investigator's Global Assessment (IGA) score of 0/1 at Week 16 [16 Weeks]

   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.

2. Eczema Area and Severity Index (EASI 75) at Week 16 [16 Weeks]

   Proportion of subjects achieving at least a 75% improvement in Eczema Area and Severity Index (EASI 75) from baseline at Week 16.

Secondary Outcome Measures

1. Worst-Itch Numeric Rating Scale (WI-NRS-4)-4 at Week 16 [Week 16]

   Proportion of subjects achieving an improvement of Worst-Itch Numeric Rating Scale (WI-NRS) ≥4 from baseline at Week 16

2. Worst-Itch Numeric Rating Scale (WI-NRS) at Week 1, 4, 8 and 12 [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.

3. Time to WI-NRS response [Baseline to Week 16]

   Time from baseline to achieve at least 4 points improvement of WI-NRS during placebo-controlled treatment phase.

4. EASI 75 at Week 1, 4, 8 and 12 [Week 1, 4, 8 and 12]

   Proportion of subjects achieving EASI 75 at all scheduled visits during placebo-controlled treatment phase except Week 16.

5. IGA 0/1 at Week 1, 4, 8 and 12 [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.

Other Outcome Measures

1. NRS-4 at Week 24, 32, 40, 52 and 56 [All scheduled visits from Week 24 - 56]

   Proportion of subjects achieving an improvement of WI-NRS ≥4 from baseline at all scheduled visits during extension treatment phase.

2. EASI 75 at Week 24, 32, 40, 52 and 56 [All scheduled visits from Week 16 24 - 56]

   Proportion of subjects achieving EASI 75 at all scheduled visits during extension treatment phase.

3. IGA 0/1 at Week 24, 32, 40, 52 and 56 [All scheduled visits from Week 24 - 56]

   Proportion of subjects achieving IGA0/1 and a reduction from baseline of ≥2 points at all scheduled visits during extension treatment phase.

4. EASI 50 and EASI 90 at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56 [Day 1 to Week 56]

   Proportion of subjects with ≥50% EASI improvement from baseline (EASI 50) at all scheduled visits.

5. Change of EASI from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56 [Day 1 to Week 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.

6. SCORAD 50, SCORAD 75 and SCORAD 90 at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56 [Day 1 to Week 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.

7. Change of SCORAD from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56 [Day 1 to Week 56]

   Change from baseline in SCORAD at all scheduled visits

8. Change of BSA from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56 [Day 1 to Week 56]

   Change from baseline in body surface area (BSA) affected at all scheduled visits

9. Change of IgE from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56 [Day 1 to Week 56]

   Change from baseline in the level of serum IgE in peripheral blood at all scheduled visits.

10. Change of eosinophils from baseline at Week 1, 4, 8, 12, 16, 24, 32, 40, 52 and 56 [Day 1 to Week 56]

    Change from baseline in the level of serum eosinophils in peripheral blood at all scheduled visits.

11. 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 [Day 1 to Week 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.

12. Change of Patient-Oriented Eczema Measure (POEM) from baseline at Week 4, 8, 12, 16, 24, 32, 40, 52 and 56 [Day 1 to Week 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dr Chih-ho Hong Medical Inc.	Surrey	British Columbia	Canada
2	Enverus Medical Research	Surrey	British Columbia	Canada
3	Wiseman Dermatology Research	Winnipeg	Manitoba	Canada
4	CCA Medical Research	Ajax	Ontario	Canada
5	SKiN Health	Cobourg	Ontario	Canada
6	DermEffects	London	Ontario	Canada
7	North York Research Inc.	North York	Ontario	Canada
8	The Centre for Dermatology	Richmond Hill	Ontario	Canada
9	Research Toronto	Toronto	Ontario	Canada
10	Toronto Research Centre	Toronto	Ontario	Canada
11	XLR8 Clinical Research	Windsor	Ontario	Canada
12	Clinique D	Laval	Quebec	Canada
13	First Affiliated Hospital of Anhui Medical University	Hefei	Anhui	China
14	Zhongshan Hospital, Fudan University(Xiamen Branch)	Xiamen	Fujian	China
15	Dermatology Hospital of Southern Medical University	Guangzhou	Guangdong	China
16	The First affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China
17	Wuhan No.1 Hospital	Wuhan	Hubei	China
18	Xiangya Hospital of Central South University	Changsha	Hunan	China	410008
19	The Second Xiangya Hospital of Central South University	Changsha	Hunan	China
20	Hospital for Skin Diseases, Chinese Academy of medical sciences	Nanjing	Jiangsu	China
21	Jiangsu province people's hospital	Nanjing	Jiangsu	China
22	Wuxi No.2 People's Hospital	Wuxi	Jiangsu	China
23	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu	China
24	Jiangxi Provincial Hospital of Dermatology	Nanchang	Jiangxi	China
25	The first hospital of jilin university	Changchun	Jilin	China
26	The Second Affiliated Hospital of Xi 'an Jiaotong	Xian	Shan XI	China
27	West China Hospital of Sichuan University	Chengdu	Sichuan	China
28	Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital	Tianjin	Tianjin	China	300120
29	The First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang	China	310003
30	The Children's Hospital Affiliated to Zhejiang University School of Medicine	Hangzhou	Zhejiang	China
31	The first people's hospital of hangzhou	Hangzhou	Zhejiang	China
32	The fourth hospital affiliated to zhejiang university school of medicine	Yiwu	Zhejiang	China
33	Peking union medical college hospital	Beijing		China	100730
34	Beijing Children's Hospital, Capital Medical University	Beijing		China
35	Children's Hospital Capital Institute of Pediatrics	Beijing		China
36	Peking University third hospital	Beijing		China
37	The Third Xiangya Hospital of Central South University	Changsha		China	410013
38	Chongqing Traditional Chinese medicine Hospital	Chongqing		China
39	First affiliated hospital of chongqing medical university	Chongqing		China
40	The Southwest Hospital of AMU	Chongqing		China
41	Zhejiang province People's Hospital	Hangzhou		China	310014
42	Dermatology hospital of Shanghai	Shanghai		China
43	Huashan Hospital Affiliated to Fudan University	Shanghai		China
44	The first hospital of China medical university	Shenyang		China	110001

Sponsors and Collaborators

• Reistone Biopharma Company Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Reistone Biopharma Company Limited
• ClinicalTrials.gov Identifier: NCT04875169
• Other Study ID Numbers: RSJ10333
• First Posted: May 6, 2021
• Last Update Posted: Jun 6, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema

Study Results

No Results Posted as of Jun 6, 2022