Abstract
Background: Recombinant human albumin (rHA) is an alternative to human serum albumin (HSA) for the management of ascites in cirrhotic patients. This phase II study was designed to evaluate dose effect, safety and immunogenicity of rHA injection in treatment of hypoalbuminemia in cirrhotic patients with ascites. It is to provide the basis for the design of Phase III clinical trial. Methods: This multicenter, blinded, positive controlled, phase II/III, adaptive design and seamless connection study enrolled 90 Chinese subjects divided into two dose cohorts(Figure 1). Each cohort included 45 subjects who were randomized 2:1 to receive rHA or HSA, respectively, at a dose of 10 g/ day (14 d of administration) or 20 g/day (7 d of administration). All subjects were followed-up for 56 days after the treatment was concluded. The primary objective was to assess the initial efficacy, dose effect, safety and immunogenicity of rHA. Efficacy was assessed by monitoring serum albumin concentration and plasma colloid osmotic pressure (PCOP) before and after each dose of rHA or HSA. The time required for the serum albumin concentration to reach 35 g/L was also monitored. Safety was determined by the incidence, intensity, and seriousness of adverse events. Results: Improvement of serum albumin concentration in the rHA cohorts was similar to that in the HSA cohorts during both treatment and follow-up. In two dose groups, the increase of the serum albumin level and PCOP in 20 g/d group were faster than those in 10 g/d group. The incidence of adverse events was similar between the rHA and has cohorts, and no dose-response relationships were observed for adverse events. No antidrug antibodies were found in an immunogenicity study. Conclusion: The efficacy and safety of rHA injection (the investigational drug) was basically the same with HSA (the control drug) in two dose groups (CTR20212001). The results of this clinical trial support the investigational drug to enter Phase III study. Since 20 g/d group has the same safety risk as 10 g/d group, and 20 g/d could increase the level of albumin and PCOP more quickly than 10 g/d, the dose of 20 g/d was recommended for Phase III study.