A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants

نویسندگان

  • Prasad S. Kulkarni
  • Sajjad Desai
  • Tushar Tewari
  • Anand Kawade
  • Nidhi Goyal
  • Bishan Swarup Garg
  • Dinesh Kumar
  • Suman Kanungo
  • Veena Kamat
  • Gagandeep Kang
  • Ashish Bavdekar
  • Sudhir Babji
  • Sanjay Juvekar
  • Byomkesh Manna
  • Shanta Dutta
  • Rama Angurana
  • Deepika Dewan
  • Abhijeet Dharmadhikari
  • Jagdish K. Zade
  • Rajeev M. Dhere
  • Alan Fix
  • Maureen Power
  • Vidyasagar Uprety
  • Varsha Parulekar
  • Iksung Cho
  • Temsunaro R. Chandola
  • Vikash K. Kedia
  • Abhishek Raut
  • Jorge Flores
  • Hanif Shaikh
  • Lalit Gupta
  • Rakesh Patil
  • Mohd. Aslam
  • Alok Arya
  • Farhana Rafiqi
  • Subodh S. Gupta
  • Chetna H. Maliye
  • P.V. Bahulekar
  • Kiran Bala
  • Tajali Nazir Shora
  • Shahid Hussain
  • Mihir Kumar Bhattacharya
  • Ashis K. Mukhopadhyay
  • Dilip Kumar Pal
  • Jayanta Saha
  • Ranjitha S. Shetty
  • Muralidhar M. Kulkarni
  • Chythra V. Raj
چکیده

Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14weeks of age along with routine vaccines. Home visit surveillance was conducted to detect severe rotavirus gastroenteritis (SRVGE) and safety outcomes until the children reached two years of age. A total of 3749 infants received BRV-PV while 3751 received placebo. At the time of the primary end-point (when the minimum number of cases needed for analysis were accrued) the vaccine efficacy against SRVGE was 36% (95% CI 11.7, 53.6, p=0.0067) in the per protocol (PP) analysis, and 41.9% (95% CI 21.1, 57.3, p=0.0005) in the intent to treat (ITT) analysis. Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5% (95% CI 26.7, 50, p<0.0001) in the PP analysis and 38.8% (95% CI, 26.4, 49, p<0.0001) in the ITT analysis. Vaccine efficacy against the very severe rotavirus cases (VSRVGE, Vesikari score≥16) was 60.5% (95% CI 17.7, 81, p=0.0131) at the time of the primary analysis and 54.7% (95% CI 29.7, 70.8, p=0.0004) for the complete follow-period in the PP population. The incidence of solicited, unsolicited, and serious adverse events were similar in both the vaccine and placebo groups. Likewise, the number of intussusceptions and deaths were similar between both groups. Thus, BRV-PV is an effective, well tolerated and safe vaccine in Indian infants. (Trial registration: Clinical Trials.Gov [NCT 02133690] and Clinical Trial Registry of India [CTRI/2013/05/003667]).

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عنوان ژورنال:

دوره 35  شماره 

صفحات  -

تاریخ انتشار 2017