Pharmacokinetic study and preliminary evaluation of safety and efficacy of the recombinant human monoclonal antibodies against rabies virus (rhRIG) in Chinese healthy population: A randomized, single-blinded, placebo-controlled phase Ia clinical trial

Background: Passive immune agents play an important role in the prevention of rabies following exposure. This trial investigated the safety, tolerability, and pharmacokinetics of recombinant human monoclonal antibodies against rabies virus (rhRIG).

Method: This clinical trial was conducted on healthy Chinese adults. The subjects were enrolled into three dosage groups. The safety of the drug was assessed, and the blood concentration of the monoclonal antibody (NM57) and the neutralizing antibody levels were measured.

Results: The rhRIG presented favorable safety and tolerability.The subjects in the low(10 IU/kg), medium(20 IU/kg), and high(40 IU/kg) dosage groups reported the C_max of 87.15 ± 18.86, 210.92 ± 77.5, and 394.11 ± 134.98 ng/ml, respectively, and the AUC_0-t of 2115.8 ± 791.3, 6064 ± 1890, and 10735.6 ± 4090 ng/mL*d, and the T_{1/2 z} of 15.82 ± 3.03, 15.96 ± 2.37, and 14.34 ± 3.84 d. The T_max of neutralizing antibody levels in the serum was about 10d (5-14d). The detectable rate of neutralizing antibody levels in the medium dosage group was close to that in the high dosage group and higher than that in the low dosage group.

Conclusions: The 10-40IU/kg rhRIG was well tolerated by the participants. The results of the pharmacokinetic analysis were consistent with the characteristics of linear elimination. The neutralizing antibody levels was positively correlated with the dosage of rhRIG.