Background SBI-087 is a humanized CD20-directed SMIP™ (mono-specific protein therapeutic) that has been shown to deplete B cells in a dose dependent manner in Phase 1 studies in subjects with stable rheumatoid arthritis (RA).

Objectives The objective of this study was to evaluate the safety and efficacy of four 200 mg subcutaneous (SC) dosing regimens versus placebo in seropositive subjects with active RA on a stable background of methotrexate (MTX).

Methods Subjects with active RA (≥5 tender joints, ≥5 swollen joints, and either C-reactive protein ≥7 mg/L or erythrocyte sedimentation rate ≥28 mm/h) were randomized to either placebo or 1 of 4 active treatment arms receiving 200 mg SBI-087 as follows: (1) Day 1; (2) Day 1, 15; (3) Day 1, Week 12; (4) Day 1, 15, and Week 12. SBI-087 was administered as two 100 mg SC injections in combination with 40 mg oral prednisone or equivalent, acetaminophen, and an antihistamine prior to dosing and 20 mg oral prednisone or equivalent 4 hours post dose. The study consisted of 2 parts: a 24 week initial phase evaluating safety and efficacy and a follow-up phase after week 24 to monitor for safety and B cell recovery. The primary outcome measure was ACR20 at week 16. Secondary outcome measures included ACR50/70 and DAS28 at week 16 and also ACR20/50/70 and DAS28 at week 24. Improvements in individual parameters such as the HAQ-DI and acute phase reactants were also assessed. All subjects were evaluated for safety.

Results 209 subjects were randomized into the study. 40 (19.1%) subjects discontinued during the initial phase of the study primarily due to adverse events (15, 7.2%) or lack of efficacy (13, 6.2%). Improvement in the ACR20 primary endpoint was seen in the Day 1, 15, and Week 12 treatment arm (relative to placebo) at week 16 (p<0.05). The ACR20/50/70 rates at week 16 were 71%/39%/12% in the Day 1, 15, and Week 12 arm versus 50%/26%/8% in the placebo arm. The DAS28 mean changes from baseline at week 16 were -2.12 in the Day 1, 15, and Week 12 arm versus -1.52 in the placebo arm (p<0.05). B cell depletion showed a clear biological response in relation to the different SBI-087 regimens engaged. The most frequently occurring adverse events in SBI-087 treated subjects (≥5 subjects), excluding infections, through the first 24 Weeks, were headache, leukopenia, pyrexia, RA exacerbation, diarrhea, nausea, and increased ALT. Most infections were mild to moderate in severity. There were no opportunistic infections. During the first 24 weeks, 11 subjects who received SBI-087 experienced serious adverse events. Only 5 subjects experienced mild to moderate injection site reactions.

Conclusions SBI-087 administered subcutaneously was generally well tolerated. The 200 mg SBI-087 Day 1, 15, and Week 12 treatment arm achieved significant improvement in RA disease activity by week 16 compared to placebo.

Disclosure of Interest N. Damjanov: None Declared, M. Tlustochowicz: None Declared, J. Aelion Grant/Research support from: Abbott, BMS, Celgene, Eli Lilly, Novartis, Pfizer, Takeda, Vertex, and UCB, Consultant for: Abbott, Amgen, Takeda, and UCB, A. Dimic: None Declared, M. Greenwald: None Declared, A. Diehl Employee of: Pfizer Inc., I. Bhattacharya Employee of: Pfizer Inc., S. Menon Employee of: Pfizer Inc., I. Gourley Employee of: Pfizer Inc.