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

Abstract

BackgroundPassive 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). MethodThis 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. ResultsThe 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 Cmax of 87.15 ± 18.86, 210.92 ± 77.5, and 394.11 ± 134.98 ng/ml, respectively, and the AUC0-t of 2115.8 ± 791.3, 6064 ± 1890, and 10735.6 ± 4090 ng/mL*d, and the T1/2 z of 15.82 ± 3.03, 15.96 ± 2.37, and 14.34 ± 3.84 d. The Tmax 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. ConclusionsThe 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.