Background/Purpose: SHR-1314 is a humanized monoclonal immunoglobulin (IgG1/κ isotype) targeting human interleukin-17A (IL-17A). Preliminary data from phase I study has shown that single dose of SHR-1314 from 8 mg to 240 mg was safe and well-tolerated in healthy subjects (data on file, Hengrui). Here, we report the interim results of a Phase II study (NCT03463187) assessing the efficacy and safety of SHR-1314 in subjects with moderate-to-severe plaque psoriasis after 12-weeks treatment.

Methods: This phase II study was conducted in 20 centers in China, Australia, and the US. Eligible subjects with moderate-to-severe chronic plaque psoriasis were randomized 1:1:1:1:1 into one of five groups to receive SHR-1314 (40 mg, 80 mg, 160 mg, or 240 mg) or placebo subcutaneously at week 0, 4, 8, and 12, followed by unblinding. The date of data cutoff for the present analyses was Dec 18, 2019, although subjects on SHR-1314 received two more drug administration on Week 16 and 20 respectively afterwards. The primary endpoint was the percentage of subjects who achieve at least 75% improvement in the psoriasis area and severity index score (PASI 75) at week 12.

Results: 187 were randomized to receive SHR-1314 at a dose of 40 mg (37 subjects), 80 mg (38 subjects), 160 mg (38 subjects), or 240 mg (37 subjects), or placebo (37 subjects). Baseline demographic and disease characteristics were similar among treatment groups (Table 1). There were significantly greater proportions of PASI 75 responders in all SHR-1314 groups (40, 80, 160, 240 mg: 56.8%, 65.8%, 81.6%, 89.2%; p< 0.001 [calculated by Chi-square test] for every SHR-1314 group) compared to placebo (5.4%) at week 12 (Figure 1A). In comparison with placebo, greater improvements over time were observed for subjects with SHR-1314 in percent change from baseline in PASI score (Figure 1B), proportion of subjects with at least 50%, 75%, or 90% improvement from baseline in PASI (PASI 50, PASI 75, or PASI 90, Figure 1C-E), and proportion of subjects achieving physician global assessment (PGA, Figure 2) response of 0 or 1. Treatment-emergent adverse events (TEAEs) were reported in 107 (71.3%) of the 150 subjects with SHR-1314 and 24 (64.9%) of 37 subjects with placebo. The most frequent TEAEs included upper respiratory tract infection (SHR-1314, 13.3%; placebo, 16.2%) and hyperuricaemia (SHR-1314, 7.3%; placebo, 5.4%). Sixty-five (43.3%) subjects with SHR-1314 and 11 (29.7%) subjects with placebo had treatment-related TEAEs. Most of TEAEs were mild or moderate. Serious TEAEs occurred in one (0.7%) subject with SHR-1314 and two (5.4%) with placebo, none were considered as treatment-related. One (0.7%) subject with SHR-1314 and one (2.7%) with placebo discontinued treatment due to TEAEs. No deaths were reported.

Conclusion: SHR-1314 showed superior efficacy compared to placebo in all groups in subjects with moderate-to-severe plaque psoriasis. 240 mg dosing led to numerically higher PASI 75 responders by week 12 than other doses. SHR-1314 was well-tolerated in the present trial.

Table 1. Baseline Demographics and Clinical Characteristics.

Figure 1. Changes from baseline in PASI score and response rates of PASI 50, PASI 75, and PASI 90. (A) Proportion of PASI 75 responders at week 12. Missing values are handled by LOCF (last observation carried forward). (B) Mean of percent change from baseline in PASI score. (C) Response rate of PASI 50 through Week 12. Missing values are handled by NCF (non-completers considered failure). (D) Response rate of PASI 75 through Week 12. Missing values are handled by NCF. (E) Response rate of PASI 90 through Week 12. Missing values are handled by NCF.

Figure 2. PGA 0 or 1 response rate through Week 12. Missing values are handled by NCF.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-multi-center-randomized-double-blind-placebo-controlled-dose-ranging-study-evaluating-efficacy-and-safety-of-shr-1314-in-subjects-with-moderate-to-severe-plaque-psoriasis/