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Abstract Number: 0201

A Multicenter, Randomized, Placebo-controlled, Double-blind Phase 2 Study of SHR0302 versus Placebo in Chinese Subjects with Moderate to Severe Active Rheumatoid Arthritis (RA)

Xiaofeng Zeng1, Ying Jiang2, Ying Yang3 and Hanying Li4, 1Department of Rheumatology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China (People's Republic), 2Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China (People's Republic), 3Jiangsu Hengrui Medicine Co., Ltd, Guangzhou, China (People's Republic), 4Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China (People's Republic)

Meeting: ACR Convergence 2020

Keywords: clinical trial, rheumatoid arthritis

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Session Information

Date: Friday, November 6, 2020

Session Title: RA – Treatments Poster I: RA Treatments & Their Safety

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Proinflammatory cytokine activation of JAK/STAT signal pathway is critical in the pathogenesis and progression of RA. SHR0302, a potent and selective inhibitor of JAK1, demonstrated promising anti-inflammatory effects for RA in both preclinical and phase 1 studies. A multicenter, randomized, placebo-controlled, double-blind phase 2 study was performed to evaluate the efficacy and safety of SHR0302 in Chinese subjects with RA.

Methods: Eligible subjects were 18–70 years; had a diagnosis of RA according to 2010 ACR/EULAR RA criteria; had moderately to severely active disease defined by ≥6 tender joints, ≥6 swollen joints (out of 68- or 66-joints examined), and ESR>28 mm/h or CRP >1.2 times upper limit of normal; were either treatment-naive or inadequately responded or intolerant to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Subjects who had prior treatment with JAK inhibitor or biologics were excluded. Eligible subjects were randomized to receive placebo or 0.5, 1, 2, or 4 mg SHR0302 in 1:1:1:1:1 (per protocol v1.1) or to receive placebo, 4 or 8 mg SHR0302 1:1:3 (per protocol v2.0) once daily (oral) for 12 weeks. Afterwards, subjects who initially assigned to placebo were re-assigned to take 2, 4 mg or 8 mg SHR0302 daily for additional 12 weeks, while subjects initially assigned to SHR0302 remained on the same treatment. The primary endpoint was the proportion of subjects who achieved ≥20% improvement according to the American College of Rheumatology response criteria (ACR20) at week 12.

Results: Between Sep 2017 to Oct 2019, 194 eligible subjects were randomized (Figure 1). The ACR20 response rates at week 12 for subjects receiving SHR0302 2 mg (56.5%, p=0.02), 4 mg (67.5%, p< 0.001), and 8 mg (77.8%, p< 0.001) were significantly greater than those of placebo (27.0%). ACR50/70 response rates at week 12 were generally consistent with ACR20 (Table 1). Mean changes from baseline in DAS28-3 (CRP) were numerically greater with the treatment of SHR0302 in comparison with placebo at week 12 (Table 1), and significantly more subjects in 4 mg (25.0%, p=0.02) and 8 mg (33.3%, p=0.002) groups achieved a DAS28-3 (CRP) < 2.6 versus placebo (5.4%) at week 12. SHR0302 2, 4, and 8 mg groups had significantly greater changes from baseline in HAQ-DI scores at week 12 (adjusted mean change: 2 mg, -0.68, p=0.02; 4 mg, -0.48, p=0.048; 8 mg -0.75, p< 0.001) as compared with placebo (-0.30). Above-mentioned improvements were sustained at week 24 (Table 1). The proportion of subjects with any treatment emergent adverse events was higher for SHR0302 (73.9%) vs placebo (62.2%) through week 12, particularly infection (Table 2). A total of four cases of herpes zoster and one case of opportunistic infection (cryptococcal pneumonia) were reported, all in SHR0302 8 mg group. No tuberculosis, malignancy, important cardiovascular events or death were reported. Safety results were presented in Table 2.

Conclusion: SHR0302 showed sustained efficacy in improving signs and symptoms of rheumatoid arthritis in a dose-dependent manner and had a generally acceptable safety profile. Further confirmatory studies with SHR0302 in RA will be planned accordingly.

Figure 1. Trial profile. The SHR0302 8 mg group was added in protocol v2.0 to explore the maximum safe and effective dose according to latest preclinical data. AE, adverse events; INV, investigator; PD, progressive disease; DC, discontinuation.

Table 1. Efficacy results. †: P < 0.05; ‡: P < 0.01 vs PBO; *: adjusted for baseline HAQ-DI score and previous inadequate response to csDMARDs or not; Data are n (%), unless otherwise specified; PBO, placebo; DAS28-3 (CRP), 3-variable 28-joint Disease Activity Score using C-Reactive Protein; HAQ-DI, Health Assessment Questionnaire Disability Index.

Table 2. Safety profile. Data are n (%), unless otherwise specified. PBO, placebo; TEAE, treatment-emergent adverse event; AESI,adverse event of special interest; MACE, major adverse cardiovascular events; VTE, venous thromboembolism.


Disclosure: X. Zeng, Jiangsu Hengrui Medicine Co., Ltd, 1; Y. Jiang, Jiangsu Hengrui Medicine Co., Ltd, 1; Y. Yang, Jiangsu Hengrui Medicine Co., Ltd, 1; H. Li, Jiangsu Hengrui Medicine Co., Ltd, 1.

To cite this abstract in AMA style:

Zeng X, Jiang Y, Yang Y, Li H. A Multicenter, Randomized, Placebo-controlled, Double-blind Phase 2 Study of SHR0302 versus Placebo in Chinese Subjects with Moderate to Severe Active Rheumatoid Arthritis (RA) [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/a-multicenter-randomized-placebo-controlled-double-blind-phase-2-study-of-shr0302-versus-placebo-in-chinese-subjects-with-moderate-to-severe-active-rheumatoid-arthritis-ra/. Accessed May 16, 2022.
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