Top

American Journal of Clinical Dermatology

Published in:

01-11-2021 | Atopic Dermatitis | Original Research Article

Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial

Authors: Yan Zhao, Litao Zhang, Yangfeng Ding, Xiaohua Tao, Chao Ji, Xiuqin Dong, Jianyun Lu, Liming Wu, Rupeng Wang, Qianjin Lu, Aik Han Goh, Rongjun Liu, Zhiguo Zhang, Jianzhong Zhang

Published in: American Journal of Clinical Dermatology | Issue 6/2021

Abstract

Background

Atopic dermatitis is a chronic, inflammatory condition causing a substantial burden to patients and caregivers. SHR0302 is an oral, highly selective, Janus kinase 1 inhibitor under investigation for inflammatory skin diseases.

Objective

The aim of this study was to investigate the efficacy and safety of SHR0302 in Chinese patients with moderate to severe atopic dermatitis.

Design and Setting

A randomized, double-blind, placebo-controlled, multicenter, phase II trial was conducted in China between October 2019 and August 2020.

Participants

Patients (n = 105) aged 18–75 years with moderate to severe dermatitis and nonresponsive or intolerant to topical or conventional systemic treatments were included.

Interventions

Patients were randomly assigned in a ratio of 1:1:1 to receive SHR0302 4 mg once daily, SHR0302 8 mg once daily, or placebo for 12 weeks.

Main Outcome Measures

The primary efficacy endpoint was the proportion of patients achieving Investigator’s Global Assessment (IGA) response (IGA of 0 [clear] or 1 [almost clear] with improvement of ≥2 grades) at week 12. Secondary efficacy assessments included Eczema Area and Severity Index (EASI) and pruritus Numerical Rating Scale (NRS) scores.

Results

At week 12, IGA response was achieved in nine patients (25.7%; 90% confidence interval [CI] 13.6–37.9%; p = 0.022) in the SHR0302 4 mg group, 19 patients (54.3%; 90% CI 40.4–68.1%; p < 0.001) in the SHR0302 8 mg group, and two patients (5.7%; 90% CI 0.0–12.2%) in the placebo group. EASI75 was achieved in 51.4% (p = 0.013), 74.3% (p < 0.001), and 22.9% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively, while an NRS ≥3-point improvement occurred in 65.7% (p < 0.001), 74.3% (p < 0.001), and 22.9% of patients, respectively. Treatment-emergent adverse events were reported in 60.0%, 68.6%, and 51.4% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively. The adverse events were mild in most cases. Three serious adverse events were reported, all being worsening of atopic dermatitis. No serious infection was reported.

Conclusions and Relevance

Oral SHR0302 was effective and well tolerated in Chinese adult patients with moderate to severe atopic dermatitis.

Trial Registration

ClinicalTrials.gov identifier: NCT04162899; URL: https://clinicaltrials.gov/. Date first registered: 14 November 2019.

Available only for authorised users

Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338–51. https://doi.org/10.1016/j.jaad.2013.10.010.CrossRefPubMed

Vakharia PP, Chopra R, Sacotte R, Patel KR, Singam V, Patel N, et al. Burden of skin pain in atopic dermatitis. Ann Allergy Asthma Immunol. 2017;119(6):548-52.e3. https://doi.org/10.1016/j.anai.2017.09.076.CrossRefPubMedPubMedCentral

Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013;132(5):1132–8. https://doi.org/10.1016/j.jaci.2013.08.031.CrossRefPubMed

Williams H, Robertson C, Stewart A, Aït-Khaled N, Anabwani G, Anderson R, et al. Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood. J Allergy Clin Immunol. 1999;103(1 Pt 1):125–38. https://doi.org/10.1016/s0091-6749(99)70536-1.CrossRefPubMed

Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. 2018;32(5):657–82. https://doi.org/10.1111/jdv.14891.CrossRefPubMed

Chiesa Fuxench ZC, Block JK, Boguniewicz M, Boyle J, Fonacier L, Gelfand JM, et al. Atopic Dermatitis in America Study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol. 2019;139(3):583–90. https://doi.org/10.1016/j.jid.2018.08.028.CrossRefPubMed

Wang X, Li LF, Zhao DY, Shen YW. Prevalence and clinical features of atopic dermatitis in China. Biomed Res Int. 2016;2016:2568301. https://doi.org/10.1155/2016/2568301.CrossRefPubMedPubMedCentral

Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM. The burden of atopic dermatitis in US adults: health care resource utilization data from the 2013 National Health and Wellness Survey. J Am Acad Dermatol. 2018;78(1):54-61.e1. https://doi.org/10.1016/j.jaad.2017.08.002.CrossRefPubMed

Eckert L, Gupta S, Gadkari A, Mahajan P, Gelfand JM. Burden of illness in adults with atopic dermatitis: analysis of National Health and Wellness Survey data from France, Germany, Italy, Spain, and the United Kingdom. J Am Acad Dermatol. 2019;81(1):187–95. https://doi.org/10.1016/j.jaad.2019.03.037.CrossRefPubMed

10.

Carroll CL, Balkrishnan R, Feldman SR, Fleischer AB Jr, Manuel JC. The burden of atopic dermatitis: impact on the patient, family, and society. Pediatr Dermatol. 2005;22(3):192–9. https://doi.org/10.1111/j.1525-1470.2005.22303.x.CrossRefPubMed

11.

Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J Invest Dermatol. 2017;137(1):26–30. https://doi.org/10.1016/j.jid.2016.07.012.CrossRefPubMed

12.

Rønnstad ATM, Halling-Overgaard AS, Hamann CR, Skov L, Egeberg A, Thyssen JP. Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: a systematic review and meta-analysis. J Am Acad Dermatol. 2018;79(3):448-56.e30. https://doi.org/10.1016/j.jaad.2018.03.017.CrossRefPubMed

13.

Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U.S. adults. Br J Dermatol. 2019;181(3):554–65. https://doi.org/10.1111/bjd.17683.CrossRefPubMedPubMedCentral

14.

Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018;121(3):340–7. https://doi.org/10.1016/j.anai.2018.07.006.CrossRefPubMed

15.

Atopic Dermatitis Working Group, Immunology Group Chinese Society of Dermatology. Guideline for diagnosis and treatment of atopic dermatitis in China (2020). Chinese Journal of Dermatology. 2020;53(2):81-8.

16.

Boguniewicz M, Alexis AF, Beck LA, Block J, Eichenfield LF, Fonacier L, et al. Expert perspectives on management of moderate-to-severe atopic dermatitis: a multidisciplinary consensus addressing current and emerging therapies. J Allergy Clin Immunol Pract. 2017;5(6):1519–31. https://doi.org/10.1016/j.jaip.2017.08.005.CrossRefPubMed

17.

Calzavara Pinton P, Cristaudo A, Foti C, Canonica GW, Balato N, Costanzo A, et al. Diagnosis and management of moderate to severe adult atopic dermatitis: a Consensus by the Italian Society of Dermatology and Venereology (SIDeMaST), the Italian Association of Hospital Dermatologists (ADOI), the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC), and the Italian Society of Allergological, Environmental and Occupational Dermatology (SIDAPA). G Ital Dermatol Venereol. 2018;153(2):133-45. https://doi.org/10.23736/s0392-0488.17.05892-8.

18.

Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116–32. https://doi.org/10.1016/j.jaad.2014.03.023.CrossRefPubMedPubMedCentral

19.

Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71(2):327–49. https://doi.org/10.1016/j.jaad.2014.03.030.CrossRefPubMedPubMedCentral

20.

Hendricks AJ, Lio PA, Shi VY. Management recommendations for dupilumab partial and non-durable responders in atopic dermatitis. Am J Clin Dermatol. 2019;20(4):565–9. https://doi.org/10.1007/s40257-019-00436-8.CrossRefPubMed

21.

Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–48. https://doi.org/10.1056/NEJMoa1610020.CrossRefPubMed

22.

Boguniewicz M, Leung DY. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233–46. https://doi.org/10.1111/j.1600-065X.2011.01027.x.CrossRefPubMedPubMedCentral

23.

Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011;2(3). https://doi.org/10.4172/2155-9899.1000110.

24.

Singh R, Heron CE, Ghamrawi RI, Strowd LC, Feldman SR. Emerging role of Janus kinase inhibitors for the treatment of atopic dermatitis. Immunotargets Ther. 2020;9:255–72. https://doi.org/10.2147/itt.s229667.CrossRefPubMedPubMedCentral

25.

Cotter DG, Schairer D, Eichenfield L. Emerging therapies for atopic dermatitis: JAK inhibitors. J Am Acad Dermatol. 2018;78(3 Suppl 1):S53–62. https://doi.org/10.1016/j.jaad.2017.12.019.CrossRefPubMed

26.

Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175(5):902–11. https://doi.org/10.1111/bjd.14871.CrossRefPubMed

27.

Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020;145(2):572–82. https://doi.org/10.1016/j.jaci.2019.08.042.CrossRefPubMed

28.

Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kaino H, Nagata T. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol. 2020;82(4):823–31. https://doi.org/10.1016/j.jaad.2019.12.015.CrossRefPubMed

29.

Bissonnette R, Maari C, Forman S, Bhatia N, Lee M, Fowler J, et al. The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis: results from a randomized double-blind placebo-controlled study. Br J Dermatol. 2019;181(4):733–42. https://doi.org/10.1111/bjd.17932.CrossRefPubMedPubMedCentral

30.

Guttman-Yassky E, Thaçi D, Pangan AL, Hong HC, Papp KA, Reich K, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;145(3):877–84. https://doi.org/10.1016/j.jaci.2019.11.025.CrossRefPubMed

31.

Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, Chan G, Feeney C, et al. Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(8):863–73. https://doi.org/10.1001/jamadermatol.2020.1406.CrossRefPubMed

32.

Simpson EL, Lacour JP, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020;183(2):242–55. https://doi.org/10.1111/bjd.18898.CrossRefPubMed

33.

Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020;396(10246):255–66. https://doi.org/10.1016/s0140-6736(20)30732-7.CrossRefPubMed

34.

Babon JJ, Lucet IS, Murphy JM, Nicola NA, Varghese LN. The molecular regulation of Janus kinase (JAK) activation. Biochem J. 2014;462(1):1–13. https://doi.org/10.1042/bj20140712.CrossRefPubMed

35.

World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4. https://doi.org/10.1001/jama.2013.281053.CrossRef

36.

Gooderham MJ, Bissonnette R, Grewal P, Lansang P, Papp KA, Hong CH. Approach to the assessment and management of adult patients with atopic dermatitis: a consensus document. Section II: tools for assessing the severity of atopic dermatitis. J Cutan Med Surg. 2018;22(1 Suppl):10s-s16. https://doi.org/10.1177/1203475418803628.CrossRefPubMed

37.

Paller AS, Kabashima K, Bieber T. Therapeutic pipeline for atopic dermatitis: end of the drought? J Allergy Clin Immunol. 2017;140(3):633–43. https://doi.org/10.1016/j.jaci.2017.07.006.CrossRefPubMed

38.

Jeon C, Yan D, Nakamura M, Sekhon S, Bhutani T, Berger T, et al. Frequency and management of sleep disturbance in adults with atopic dermatitis: a systematic review. Dermatol Ther (Heidelb). 2017;7(3):349–64. https://doi.org/10.1007/s13555-017-0192-3.CrossRefPubMedPubMedCentral

39.

Kapur S, Watson W, Carr S. Atopic dermatitis. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):52. https://doi.org/10.1186/s13223-018-0281-6.CrossRefPubMedPubMedCentral

40.

Atopic Dermatitis Working Group, Immunology Group, Chinese Society of Dermatology. Guideline for diagnosis and treatment of atopic dermatitis in China. Chinese Journal of Dermatology. 2020;53(2):81-8.

41.

Nezamololama N, Fieldhouse K, Metzger K, Gooderham M. Emerging systemic JAK inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib. Drugs Context. 2020;9:2020-8-5. https://doi.org/10.7573/dic.2020-8-5.

42.

He H, Guttman-Yassky E. JAK inhibitors for atopic dermatitis: an update. Am J Clin Dermatol. 2019;20(2):181–92. https://doi.org/10.1007/s40257-018-0413-2.CrossRefPubMed

Title: Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial
Authors: Yan Zhao
Litao Zhang
Yangfeng Ding
Xiaohua Tao
Chao Ji
Xiuqin Dong
Jianyun Lu
Liming Wu
Rupeng Wang
Qianjin Lu
Aik Han Goh
Rongjun Liu
Zhiguo Zhang
Jianzhong Zhang
Publication date: 01-11-2021
Publisher: Springer International Publishing
Keyword: Atopic Dermatitis
Published in: American Journal of Clinical Dermatology / Issue 6/2021
Print ISSN: 1175-0561
Electronic ISSN: 1179-1888
DOI: https://doi.org/10.1007/s40257-021-00627-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial

Abstract

Background

Objective

Design and Setting

Participants

Interventions

Main Outcome Measures

Results

Conclusions and Relevance

Trial Registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objective

Design and Setting

Participants

Interventions

Main Outcome Measures

Results

Conclusions and Relevance

Trial Registration

Please log in to get access to this content

Other articles of this Issue 6/2021

The Use of Lasers and Light Devices in Acne Management: An Update

Investigational Treatments for Epidermolysis Bullosa

Comment on: Drug Survival of IL‑12/23, IL‑17 and IL‑23 Inhibitors for Psoriasis Treatment: A Retrospective Multi‑Country, Multicentric Cohort Study

Psychosocial Effects of Vitiligo: A Systematic Literature Review

Phase II, Double-Blind, Vehicle-Controlled Study to Determine the Cantharidin Dose Regimen, Efficacy, Safety, and Tolerability of VP-102 in Subjects with External Genital Warts

Steroid Phobia: A Review of Prevalence, Risk Factors, and Interventions