Human Vaccines & Immunotherapeutics (Dec 2023)

Phase III randomized clinical studies to evaluate the immunogenicity, lot-to-lot consistency, and safety of ROTAVAC® liquid formulations (ROTAVAC 5C & 5D) and non-inferiority comparisons with licensed ROTAVAC® (frozen formulation) in healthy infants

  • Krishna Kumari P,
  • Siddharth Reddy Chiteti,
  • Vinay K. Aileni,
  • Sudhir Babji,
  • William C. Blackwelder,
  • Ashok Kumar,
  • Jayant Vagha,
  • Uma Nayak,
  • Monjori Mitra,
  • Narayanaappa D,
  • Sonali Kar,
  • Sangeeta Yadav,
  • Swamy Naidu,
  • Niranjan Mahantshetti,
  • Vasant Khalatkar,
  • Satyajit Mohapatra,
  • P. K. Purthi,
  • Pawan Sharma,
  • A. Kannan,
  • Ramchandra Keshav Dhongade,
  • Sai D. Prasad,
  • Raches Ella,
  • Krishna Mohan Vadrevu

DOI
https://doi.org/10.1080/21645515.2023.2278346
Journal volume & issue
Vol. 19, no. 3

Abstract

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ABSTRACTThe WHO pre-qualified rotavirus vaccine, ROTAVAC®, is derived naturally from the neonatal 116E rotavirus strain, and stored at −20°C. As refrigerator storage is preferable, immunogenicity and safety of liquid formulations kept at 2–8°C, having excipients to stabilize the rotavirus, with or without buffers, were compared with ROTAVAC® in different clinical studies. Study-1, the pivotal trial for this entire product development work, was a randomized, single-blind trial with two operationally seamless phases: (i) an exploratory phase involving 675 infants in which two formulations, ROTAVAC 5C (LnHRV-1.5 mL and LnHRV-2.0 mL) containing buffer and excipients to stabilize the virus against gastric acidity and temperature, were compared with ROTAVAC®. As the immune response of ROTAVAC 5C (LnHRV-2.0 mL) was non-inferior to ROTAVAC®, it was selected for (ii) confirmatory phase, involving 1,302 infants randomized 1:1:1:1 to receive three lots of LnHRV-2.0 mL, or ROTAVAC®. Primary objectives were the evaluation of non-inferiority and lot-to-lot consistency. The secondary objectives were to assess the safety and interference with the concomitant pentavalent vaccine. As it was separately established that buffers are not required for ROTAVAC®, in Study-2, the safety and immunogenicity of ROTAVAC 5D® (with excipients) were compared with ROTAVAC® and lot-to-lot consistency was assessed in another study. All lots elicited consistent immune responses, did not interfere with UIP vaccines, and had reactogenicity similar to ROTAVAC®. ROTAVAC 5C and ROTAVAC 5D® were immunogenic and well tolerated as ROTAVAC®. ROTAVAC 5D® had comparable immunogenicity and safety profiles with ROTAVAC® and can be stored at 2–8°C, leading to WHO pre-qualification.Clinical Trials Registration: Clinical Trials Registry of India (CTRI): CTRI/2015/02/005577CTRI/2016/11/007481 and CTRI/2019/03/017934.

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