A randomized, open-labelled, non-inferiority phase 4 clinical trial to evaluate the immunogenicity and safety of the live, attenuated, oral rotavirus vaccine, ROTAVAC® in comparison with a licensed rotavirus vaccine in healthy infants. Issue 31 (18th July 2019)

• Record Type: Journal Article
• Authors: Ella, Raches; Babji, Sudhir; Ciarlet, Max; Blackwelder, William C.; Vadrevu, Krishna Mohan
• Is Part Of: Vaccine. Volume 37:Issue 31(2019)
• Page Start: 4407
• Page End: 4413
• Publication Date: 2019-07-18
• Subjects: Rotavirus vaccine -- nHRV -- ROTAVAC -- Immunogenicity -- Oral vaccine -- Diarrhoea -- Rotarix -- RV1; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.05.069
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: Background: ROTAVAC® (nHRV), derived naturally from the human 116E rotavirus (RV) neonatal strain, was licensed in India in 2015 based on promising results of a phase 3, safety and efficacy vaccine trial. As a pre-requisite for WHO prequalification, we compared the immunogenicity and safety of ROTAVAC® to those of a WHO-prequalified, Rotarix®. Methods: We conducted a multicentre, open-labeled, randomized phase 4 clinical trial where 464 infants, 6–8 weeks of age were equally randomized to receive as licensed, the complete regimen of ROTAVAC® (3 doses; Group I) or Rotarix® (2 doses; Group II). Antibody responses (serum anti-RV Immunoglobulin A [IgA]) were measured by enzyme-linked immunosorbent assay (ELISA). The primary analysis was an assessment of non-inferiority of ROTAVAC® to Rotarix® for geometric mean concentration (GMC) for infants who received the complete regimen of either vaccine. Results: The GMC for Group I was 20.4 (95%CI: 17.6, 23.6) and that for Group II was 24.8 (95%CI: 20.3, 30.3), the GMC ratio was 0.82 (95% CI: 0.64, 1.05), thus meeting the non-inferiority criterion. Site-wise analysis of GMC titres revealed that one site had a peculiar pre-vaccination titre affecting only ROTAVAC® post-vaccination GMCs. Seroconversion rates were 35.3% (95%CI: 29.0, 41.9) and 31.0% (95%CI: 25.1, 37.4) for Groups I and Group II, respectively. There was no substantive difference in safety profiles between both vaccines. Conclusions: The complete regimen of ROTAVAC® demonstrated immunological non-inferiority to the complete regimen of Rotarix® with a clinically acceptable safety profile. Because the demand for RV vaccines is increasing as more countries are expanding their immunization schedules, the lack of need of a buffering agent, low dose volume (0.5 mL), non-interference with other concomitantly administered vaccines, and conformance with WHO-prequalification requirements provide ROTAVAC® the potential for widespread global usage. Post completion of this study, ROTAVAC® is now a WHO-prequalified vaccine. Clinical Trials Registration: (CTRI Number: CTRI/2015/12/006428).