Safety, pharmacokinetics and pharmacodynamics of SYN023 alone or in combination with a rabies vaccine: An open, parallel, single dose, phase 1 bridging study in healthy Chinese subjects

• Published in: Antiviral research Vol. 184; p. 104956
• Main Authors: Ding, Yanhua, Wu, Min, Zhang, Hong, Zhu, Xiaoxue, Hu, Yue, Li, Xiaojiao, Liu, Jingrui, Tsao, Eric, Liu, Ming, Li, Cuiyun
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2020
• Subjects: Anti-drug antibodies; Pharmacodynamics; Pharmacokinetics; Safety; SYN023; Pharmacodynamics; Safety; Pharmacokinetics; Anti-drug antibodies; SYN023
• ISSN: 0166-3542; 1872-9096; 1872-9096
• DOI: 10.1016/j.antiviral.2020.104956

SYN023, a mixture of two anti-rabies humanized monoclonal antibodies (mAbs), namely, CTB011 and CTB012, has been developed as a safe and cost-effective alternative to RIG in the use of postexposure prophylaxis (PEP) after rabies exposure. This phase I bridging study was designed to compare the pharmacokinetics (PK) of SYN023 (0.3 mg/kg) alone (cohort A, n = 8) or in combination with a rabies vaccine (cohort B, n = 24) in healthy Chinese subjects with those in American subjects to guide the design of further clinical trials. Their safety was assessed for the development of adverse events (AEs) by laboratory examinations. The levels of serum CTB011, CTB012 and anti-drug antibodies (ADAs) were measured longitudinally for 85 days. Serum rabies virus neutralizing antibody (RVNA) levels were measured as a pharmacodynamic (PD) surrogate. Some subjects with injectable SYN023 at 0.3 mg/kg developed temporary AEs and adverse drug reactions (ADRs) of Grade 1 or 2, particularly in cohort B, probably due to vaccine coadministration. SYN023 injection displayed a typical and reliable PK, similar to that of human IgGs. Following injection with SYN023, Chinese subjects had slower absorption with higher exposures for CTB011 but lower exposures for CTB012 than American subjects. The SYN023 recipients achieved protective levels of RVNA (≥0.5 IU/mL) on day 3 post injection. A few subjects developed temporary ADA, which did not affect the safety and PK/PD of SYN023 in Chinese subjects. SYN023 at 0.3 mg/kg is relatively saf e and effective and can be selected for further clinical trials in Chinese subjects. The clinical trial registration number is CTR20190281. http://www.chinadrugtrials.org.cn/eap/clinicaltrials.searchlist?a=a&reg_no=CTR20190281. •SYN023, a mixture of two anti-rabies humanized monoclonal antibodies (mAb), CTB011 and CTB012.•SYN023 was relatively safe and had good PK/PD profiles in healthy Chinese subjects.•SYN023 may be developed as a safe and cost-effective alternative of RIG after rabies infection.