Phase I Study Evaluating Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of Recombinant Human Serum Albumin (rHSA) in Healthy Adults.

PURPOSE: To compare the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of recombinant human serum albumin (rHSA) with plasma-derived human serum albumin (pdHSA) following intravenous administration to healthy adults.

PATIENTS AND

METHODS

This Phase I study enrolled 62 healthy adults aged 18-45 years in two sequential parts. Part 1 (n=12) evaluated safety and tolerability of rHSA using a single ascending dose design (10 g, 20 g and 40 g) with 3 cohorts. Based on these outcomes, Part 2 (n=50) was conducted as a randomized (1:1), active-controlled, parallel-group study comparing rHSA with pdHSA (Flexbumin® 20%) administered at escalating doses (10 g, 20 g, and 40 g) with 3-week intervals. Primary PK endpoints were Cmax (1st dose) and AUC∞ (3rd dose). Secondary endpoints included PK parameters: Tmax (Time to peak concentration), t½ (Elimination half-life), Elimination rate constant (Kel) and CL (Clearance). PD markers: Colloid Osmotic Pressure (COP) and Hematocrit Ratio (HCT), Safety, Tolerability, and Immunogenicity.

RESULTS

In Part 1, rHSA was tolerated up to 40 g as single dose, and at cumulative dose of 70 g in part 2, with no dose-limiting toxicities. PK and PD profiles were comparable between test rHSA and pdHSA, with geometric mean ratios for Cmax and AUCt (baseline uncorrected) falling within the accepted 80-125% bioequivalence range. COP and HCT ratios were consistent across doses, indicating equivalent pharmacodynamic activity. No severe adverse events (SAEs) occurred during the study. All reported adverse events (AE) were mild-to-moderate in severity and resolved without sequelae. Low-titre IgG antibodies were detected in a few participants, without clinical relevance, with no IgE or anti-host cell protein (HCP) antibodies detected.

CONCLUSION

The test rHSA was well tolerated at cumulative doses of 70 g and demonstrated comparable PK, PD, safety and immunogenicity profiles to pdHSA, supporting its potential as a viable alternative.