Pharmacokinetics, Safety, and Immunogenicity of DMB-3115, a Ustekinumab Biosimilar for Immune-Mediated Diseases, in Healthy Japanese Male Participants: A Randomized, Double-Blind, Single-Dose Study.

INTRODUCTION: DMB-3115 is a biosimilar to ustekinumab (Stelara®). We conducted a randomized controlled study to determine the similarity of bioavailability between DMB-3115 and Stelara (distributed in Japan) in healthy Japanese participants. METHODS: Healthy Japanese male participants aged 18 to 55 years were randomly assigned in a 1:1 ratio to receive a single subcutaneous injection (45 mg) of DMB-3115 or Stelara. Participants were followed for 112 days. The primary pharmacokinetic (PK) endpoints were area under the concentration-time curve from time zero to the final sampling time point t (AUCt) and maximum serum concentration (Cmax). RESULTS: This study was conducted between April 11, 2022 and November 22, 2022. A total of 150 participants (75 in each group) received the study drug and were included in the safety analysis, whereas 147 participants (74 in the DMB-3115 group and 73 in the Stelara group) with properly measured PK data were included in the PK analysis. The 90% confidence interval (CI) for the geometric least squares mean (LSM) ratio (DMB-3115/Stelara) of AUCt (n = 74/73) ranged from 0.826 to 1.011, which was contained within the prespecified bioequivalence range of 0.80 to 1.25. By contrast, the 90% CI for the geometric LSM ratio of Cmax (n = 74/73) ranged from 0.762 to 0.984. The proportion of participants experiencing any adverse event (AE) was 37.3% (28 participants) in the DMB-3115 group and 48.0% (36 participants) in the Stelara group. The most common AE in the DMB-3115 group (n = 75) was blood creatine phosphokinase increased. All AEs were mild or moderate in severity. The proportions of participants with post-dose anti-drug antibodies and neutralizing antibodies were lower in the DMB-3115 group (n = 75). CONCLUSION: Bioavailability of DMB-3115 was considered similar to that of Stelara in the Japanese population. DMB-3115 was well tolerated without any new safety concern. TRIAL REGISTRATION: Clinical Trial Registration Japan Registry of Clinical Trials (jRCT2071210135; registered March 22, 2022).