Comparison of Pharmacokinetic Similarity, Immunogenicity, and Safety of Ustekinumab and BAT2206 in Healthy Chinese Male Subjects in a Double-Blind, Randomized, Single-Dose, Parallel-Group Phase I Trial.

OBJECTIVE

We aimed to evaluate the similarity of BAT2206 to its originator, ustekinumab, including pharmacokinetic profiles, immunogenicity, and safety in healthy Chinese male subjects.

METHODS

This was a double-blinded, randomized, single-dose, parallel-group clinical trial, in which 270 healthy male subjects were enrolled to receive a single subcutaneous injection (45 mg) of either BAT2206 or ustekinumab (European Union or USA) at a 1:1:1 ratio. The pairwise pharmacokinetic similarities and the safety and immunogenicity of both drugs were evaluated and compared.

RESULTS

The results showed that the 90% confidence interval of the geometric mean ratio for primary pharmacokinetic parameters (maximum plasma concentration and area under the plasma concentration-time curve from time zero to infinity) among BAT2206 and ustekinumab (USA or European Union sourced) groups were all within the predefined equivalent interval of 80-125%. Furthermore, all the groups had similar incidences of treatment-emergent adverse events, in which the majority of cases belonged to Common Terminology Criteria for the Classification of Adverse Events Grade 1 or 2. Anti-drug antibodies were detected in 54 (20.1%) subjects, namely 24 (26.7%), 13 (14.8%), and 17 (18.9%) patients in the BAT2206, ustekinumab (European Union), and ustekinumab (USA) groups, respectively. In contrast, the incidences of positive neutralizing antibodies were similar among the three groups.

CONCLUSIONS

Pharmacokinetic similarity between BAT2206 and ustekinumab (USA or European Union sourced) was confirmed. The three groups had similar safety profiles, and the investigational drugs were well tolerated by subjects.

CLINICAL TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT04371185).