Clinical immunogenicity and pharmacokinetic assessments of E3112, a recombinant human hepatocyte growth factor.

Aims: E3112 is a recombinant human hepatocyte growth factor (HGF) intended for the treatment of acute liver failure. As the presence of anti-drug antibody (ADA) against E3112 could pose a significant risk in clinical settings if it cross-reacts with the body's natural HGF, we have developed assays for E3112 and its ADA in human serum.

Methods: Assays of E3112 and its ADA developed by ligand binding assays were validated in accordance with bioanalytical guidelines and applied to clinical pharmacokinetic (PK) and immunogenicity assessments.

Results: These assays demonstrated the ability to detect E3112 at a concentration as low as 0.156 ng/mL, whereas the sensitivity of ADA was determined to be 42.3 ng/mL. The validation studies, incorporating quality control for the PK assay and positive control of ADA, substantiated the reproducibility of the assays. The ADA and PK assays were applied to the real sample assays supporting a clinical trial of E3112. Following the intravenous administration of E3112, serum E3112 levels declined with a half-life of 19.3 h. No ADA was detected in predose or postdose samples.

Conclusion: These findings collectively indicate that E3112 exhibited a favorable PK profile with minimal immunogenicity within the clinical context.