A Safety and Pharmacokinetics Study in Participants With Rheumatoid Arthritis

Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs regardless of causality. A summary of s SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

AUC0-168 hr,ss of individual participants was calculated by equation AUC=Dose/Clearance (CL), where the CL was estimated using a population PK model.

Time frame for Part B: Day 1 predose, immediately after infusion (IAI), Day 14 and 28: predose and IAI, and Day 63 (Convenient time);

SDAI is calculated as the sum of 5 components: tender joint count (TJC) and swollen joint count (SJC), Patient Global Assessment (PtGA) of disease activity visual analog scale (VAS) and Physician's Global Assessment of Disease Activity (PGA) VAS, and C-reactive protein (CRP). Total Score scale range is 0 (remission) to 86 (high disease activity). A negative change from baseline indicated an improvement. Least Squares (LS) mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time.

DAS28-4 (crp) is a modification of the original DAS based on TJC and SJC based on 28 joint counts, PGA VAS. DAS28-4 (crp) calculated as: 0.56*square root (sqrt) (TJC)+0.28*sqrt(SJC)+0.36*ln(CRP+1)+0.014*PGA+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. A decrease in DAS28-CRP indicated an improvement in participant's condition.

LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time.

CRP is a biomarker associated with inflammation and structural damage. A negative change from baseline indicates improvement. LS mean calculated using a repeated measures model and adjusted for baseline + treatment + time + treatment * time.

HAQ was a participant-reported questionnaire that consisted of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). The highest score for any question in a category was the score of that category unless special aids or devices or help from another person was required. Answers for at least 6 of the 8 disability domains were required to compute the participant's HAQ score. If the participant had scores for fewer than 6 categories, the HAQ score was considered missing. The HAQ score was calculated as the sum of the category scores divided by the number of categories scored, with a possible scores range from 0 to 3. Negative mean changes from baseline indicated improvement.