DISCUSSION
PD, deaths
INJECTION SITE REACTION, HYPERSENSITIVITY REACTION
This was the first study to administer GSK3772847 subcutaneously. GSK3772847 was administered in three injection sites (upper arm, abdomen, or thigh) in healthy volunteers, including cohorts of Chinese and Japanese participants. Both the 70 and 140 mg doses were generally well tolerated with no reported injection site reactions during the study. The majority of AEs were mild, considered unrelated to the study medication, resolved without treatment, and there was no trend related to the injection site. There were six clinical chemistry‐related AEs, which were also considered mild and unrelated to the study treatment. There were no SAEs or deaths.Pharmacokinetics parameters were similar across the different injection sites with overlapping confidence intervals, indicating that the location of the injection site does not appear to affect drug availability. As expected, 
In previous studies, PK and PD modeling suggested an IV administration of GSK3772847 1 mg/kg every 2 weeks would provide adequate systemic drug exposure for effective inhibition of the IL‐33R signaling pathway in 90% of participants.As an endogenous marker for CYP3A4 activity, this study assessed changes in the plasma 4βOHC/C ratio. CYP3A4 is a member of the Cytochrome P450 family of enzymes, which catalyze reactions in the metabolism of a large proportion of drugs and contribute to variation in drug pharmacokinetics.Treatment with mAbs, including GSK3772847, may be associated with the development of antibodies against the therapeutic agent, and participants who develop antibodies to therapeutic proteins may be more likely to experience a hypersensitivity reaction or a decrease in efficacy. During this study, only one participant from cohort 4 had confirmed positive results for anti‐GSK3772847 binding antibodies on Day 57 and Day 85.This was the first study to evaluate the SC dosing of GSK3772847 in healthy volunteers, including cohorts of Japanese and Chinese participants, which assessed the injection site, dose level, and ethnic group impact on PK and PD. Although the number of participants in this study was small, it was sufficiently powered to ensure an adequate understanding of the tolerability of GSK3772847 when dosed subcutaneously and would enable the estimation of the key PK parameters. In summary, GSK3772847 was well tolerated via the SC route, delivered an exposure and target engagement profile consistent with expectations based on data from the IV route