Shortening intradermal rabies post-exposure prophylaxis regimens to 1 week: Results from a phase III clinical trial in children, adolescents and adults

• Published in: PLoS neglected tropical diseases Vol. 12; no. 6; p. e0006340
• Main Authors: Kerdpanich, Phirangkul, Chanthavanich, Pornthep, De Los Reyes, Mari Rose, Lim, Jodor, Yu, Delia, Ama, Ma. Cecilia, Mojares, Zenaida, Casula, Daniela, Arora, Ashwani Kumar, Pellegrini, Michele
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2018; Public Library of Science (PLoS)
• Subjects: Adolescents; Adults; Age; Analysis; Animal bites; Animal embryos; Antibodies; Biology and Life Sciences; Cell culture; Children; Clinical trials; Confidence intervals; Disease; Disease control; Disease prevention; Disease prophylaxis; Drug dosages; Exposure; Health aspects; Immunogenicity; Immunoglobulins; Laboratories; Lyssavirus; Medicine and Health Sciences; Pediatrics; Profiles; Prophylaxis; Rabies; Research and Analysis Methods; Safety; Supervision; Tropical diseases; Vaccination; Vaccines; Viruses; Youth; Italy; Thailand; Philippines; Bangkok Thailand
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0006340

This phase III clinical trial compared the immunogenicity and safety of a purified chick-embryo cell rabies vaccine (PCECV) administered according to a shortened post-exposure prophylaxis (PEP) 4-site/1-week intradermal regimen, compared with the currently recommended 2-site/Thai Red Cross (TRC) regimen. This controlled, open-label, multi-center study (NCT02177032) enrolled healthy individuals ≥1 year of age, randomized into 4 groups to receive intradermal PCECV according to one of the 2 regimens, with or without human rabies immunoglobulin (HRIG) administration at first visit (in adults only). Rabies virus neutralizing antibody (RVNA) concentrations and percentages of participants with RVNA concentrations ≥0.5 IU/mL (considered as adequate concentrations following PEP) were assessed up to day (D) 365 post-first vaccination. Non-inferiority of the 4-site/1-week regimen to the 2-site/TRC regimen was demonstrated if at D49, the lower limit of the 95% confidence interval (CI) for the difference between groups in the percentage of participants with adequate RVNA concentrations was >-5%. Of the 443 participants receiving the 4-site/1-week regimen, 88 adults received HRIG; 442 participants received the 2-site/TRC regimen (88 with HRIG). All participants achieved adequate RVNA concentrations by D14. At D49, the difference in percentage of participants with adequate RVNA concentrations between the 4-site/1-week and the 2-site/TRC groups was -1 (95%CI: -2.4-0.0); thus, non-inferiority was concluded. RVNA geometric mean concentrations were 18 IU/mL in 4-site/1-week groups and 12 IU/mL in 2-site/TRC groups at D14, and subsequently declined in all groups. RVNA concentrations were consistently lower in adults with HRIG administration than in those without. The 2 regimens had similar safety profiles. Of the 15 serious adverse events reported in 4-site/1-week groups and 19 in 2-site/TRC groups, none were vaccination-related. The data suggest that the 4-site/1-week regimen might be an alternative to current recommendations, with potential benefits in terms of improved cost-efficiency and compliance to vaccination.