A phase 2b, Randomized, double blinded comparison of the safety and efficacy of the monoclonal antibody mixture SYN023 and human rabies immune globulin in patients exposed to rabies.

Autor: Quiambao BP; Research Institute for Tropical Medicine Filinvest Corporate City, Muntinlupa City, Metro Manila, Philippines., Payumo RA; Mary Johnston Hospital, Tondo Manila, Metro Manila, Philippines., Roa C; Manila Doctors Hospital, Ermita Manila, Metro Manila, Philippines., Borja-Tabora CF; Center of Excellence in Drug Research, Evaluation and Studies, Inc., Filinvest Corporate City, Muntinlupa City, Metro Manila, Philippines., Emmeline Montellano M; Far Eastern University - Nicanor Reyes Medical Foundation, Quezan City, Metro Manila, Philippines., Reyes MRL; Research Institute for Tropical Medicine Filinvest Corporate City, Muntinlupa City, Metro Manila, Philippines., Zoleta-De Jesus L; Angelo King Medical Research Center, De la Salle Health Sciences Institute, Dasmarinas City, Cavite, Philippines., Capeding MR; Asian Hospital and Medical Center, Muntinlupa City, Metro Manila, Philippines., Solimen DP; Baguio General Hospital and Medical Center, Baguio City, Cordillera Administrative Region, Philippines., Barez MY; Southern Philippines Medical Center, Dermatology Clinical Research Unit, Davao City, Davao Region (Region XI), Philippines., Reid C; Synermore Biologics (Suzhou) Co., Ltd, Suzhou Industrial Park, China., Chuang A; Synermore Biologics (Suzhou) Co., Ltd, Suzhou Industrial Park, China., Tsao E; Synermore Biologics (Suzhou) Co., Ltd, Suzhou Industrial Park, China. Electronic address: etsao@synermore.com., McClain JB; Synermore Biologics (Suzhou) Co., Ltd, Suzhou Industrial Park, China.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2024 Sep 17; Vol. 42 (22), pp. 126018. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1016/j.vaccine.2024.05.066
Abstrakt: Background: SYN023 is an anti-rabies monoclonal antibody mixture administered as part of post-exposure prophylaxis regimens. The rabies virus neutralizing antibody (RVNA) concentration generally accepted as an adequate immune response to vaccination is ≥ 0.5 IU/mL.
Methods: Within 54 h of potential rabies exposure, 448 patients in two risk substrata of WHO Category III exposure were randomized to receive either 0.3 mg/kg SYN023 or 0.133 mL/kg human rabies immunoglobulin (HRIG) injected in and around the wound site(s) plus a course of rabies vaccination. Patients were followed for safety and absence of rabies for ≥ 365 days.
Results: GMT RVNA was higher with SYN023 throughout the 2-week post-treatment period. In the primary analysis group (n = 368), 99.4 % of SYN023 recipients versus 4.5 % of HRIG recipients had protective RVNA levels on Day 4. On Day 8, 98.1 % SYN023 versus 12.2 % HRIG recipients were protected. The SYN023:HRIG ratio of geometric mean titer of RVNA (RVNA GMTs) on Day 8 (19.42) exceeded the 10 % superiority margin (P < 0.0001) indicating higher Day 8 RVNA with SYN023. On Day 99, the SYN023:HRIG RVNA GMT ratio (0.66) was below the non-inferiority margin of 20 % (P = 0.9485) suggesting some moderation of vaccine immune response by SYN023 relative to HRIG. The ratio of percent SYN023:HRIG recipients achieving RVNA ≥ 0.5 IU/mL on Day 99 (0.98) met the non-inferiority margin of 20 % (P = 0.013) indicating anti-rabies immune response with SYN023 was non-inferior to HRIG despite this effect. There were no probable/confirmed rabies cases in any patient. Study regimens were well tolerated.
Conclusions: SYN023 provided higher RVNA than HRIG soon after rabies exposure. By Day 99 post-treatment, GM RVNA with SYN023 was lower than HRIG, however, the percent of SYN023 recipients with a protective response was not inferior at this time point. No rabies cases were reported in the study. The SYN023 safety profile was acceptable.
Clinicaltrials: gov ID: NCT03961555.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [A.C. and E.T. are employed by Synermore Biologics (Suzhou) Co. C.R. and J.B.M. are paid consultants to Synermore Biologics (Suzhou) Co.].
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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