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

• Published in: Vaccine Vol. 42; no. 22; p. 126018
• Main Authors: Quiambao, Beatriz P., Payumo, Ronald Allan, Roa, Camilo, Borja-Tabora, Charissa Fay, Emmeline Montellano, May, Reyes, Mari Rose De Los, Zoleta-De Jesus, Loreta, Capeding, Maria Rosario, Solimen, Domingo P., Barez, Marie Yvette, Reid, Caroline, Chuang, Ariel, Tsao, Eric, McClain, J. Bruce
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 17.09.2024; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Bats; Child; Clinical trial; Double-Blind Method; Drug dosages; Enrollments; Exposure; Female; Globulins; Humans; Immune response; Immune system; Immunoglobulins; Infections; Lyssavirus; Male; Middle Aged; Mixtures; Monoclonal antibodies; Monoclonal antibody; Patients; Pharmacists; Post-exposure prophylaxis; Post-Exposure Prophylaxis - methods; Prophylaxis; Rabies; Rabies - immunology; Rabies - prevention & control; Rabies Vaccines - administration & dosage; Rabies Vaccines - adverse effects; Rabies Vaccines - immunology; Rabies Vaccines - therapeutic use; Rabies virus - immunology; Rabies virus neutralizing activity (RVNA); Response rates; Safety; Sanitation; Skin; Vaccine; Vaccines; Viruses; Young Adult; India; Clinical trial; Post-exposure prophylaxis; Vaccine; Monoclonal antibody; Rabies virus neutralizing activity (RVNA); Rabies
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2024.05.066

•SYN023-004: a large, one-year, randomized, double blind, controlled, rabies PEP study in Category III patients.•SYN023 is comprised of two humanized monoclonals against non-overlapping rabies virus epitopes.•SYN023 produces rapid and higher RVNA during the 2-week period after administration.•SYN023 safety profile appears similar to human rabies immunoglobulin. 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. 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. 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. 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.