Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis.
BACKGROUND
KHK4083, a fully human anti-OX40 monoclonal antibody, is a potential novel therapeutic option for moderate to severe atopic dermatitis (AD), targeting the immunopathogenic pathways.


OBJECTIVE
Assess the safety and tolerability of repeated doses of KHK4083 in patients with moderate to severe AD, and investigate the pharmacokinetics and immunogenicity of KHK4083. Additionally, assess the clinical efficacy and pharmacodynamics as exploratory objectives.


METHODS
In this phase 1, single-center, open-label, repeated-dose study, a total of 22 patients received KHK4083 10 mg/kg IV on Day 1, Day 15 and Day 29, and were followed until Day 155.


RESULTS
There were no deaths, serious adverse events (SAEs), or discontinuations due to adverse events (AEs). Common treatment-emergent AEs were mild or moderate pyrexia (11 patients, 50.0 %), and chills (8 patients, 36.4 %). No clinically meaningful changes in the laboratory values, vital signs, and electrocardiogram recordings were observed. The Cmax was 267 ± 53 μg/mL and the t1/2 was 303 ± 88 h at Day 29. The overall assessment of antibodies against KHK4083 (immunogenicity) showed low positive responses. Continued improvement in the Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA) scores were observed throughout the study. The mean and median percent changes in thymus and activation-regulated chemokine (TARC) continued to decrease over time to -70.4 and -78.8 % until Day 155.


CONCLUSION
Repeated intravenous infusion of KHK4083 had an acceptable safety profile in patients with moderate to severe AD. Sustained improvement in the symptoms of AD was observed after completion of KHK4083 treatment.
['Nakagawa|Hidemi|H|', 'Iizuka|Hajime|H|', 'Nemoto|Osamu|O|', 'Shimabe|Munetake|M|', 'Furukawa|Yasunobu|Y|', 'Kikuta|Natsuko|N|', 'Ootaki|Kenji|K|']
D000328:Adult D061067:Antibodies, Monoclonal, Humanized D023341:Chills D003876:Dermatitis, Atopic D004334:Drug Administration Schedule D005260:Female D005334:Fever D006801:Humans D007262:Infusions, Intravenous D007564:Japan D008297:Male D008875:Middle Aged D053278:OX40 Ligand D012720:Severity of Illness Index D016896:Treatment Outcome
Atopic dermatitis Phase 1 OX40