Immunogenicity and safety of IXIARO® (IC51) in a Phase II study in healthy Indian children between 1 and 3 years of age
Introduction
Japanese encephalitis (JE) is the most common virus-induced encephalitis in Asia and the JE virus causes over 50,000 cases annually [1]. The disease is endemic in many countries in Asia and about three billion individuals are at risk of infection. Most inhabitants of endemic countries are infected before reaching adulthood. The majority of infections are asymptomatic. However, in endemic countries encephalitis is diagnosed in only 1 of every 50–1000 infected individuals and diagnostic confirmation of JE is not routinely established in most countries [2]. About 25% of symptomatic JE patients die from their disease and 50% are left with permanent neurologic or psychiatric sequelae [1]. Sporadic epidemics in less endemic areas cause many thousand cases annually. JE epidemics in previously non-affected geographic locations have been noted in recent years, such as in Sri Lanka or Nepal. This incidence rise may be attributed to the introduction of rice cultivation and simultaneous growth of the population [3]. JE cases have also been reported in industrialized countries in travellers to endemic areas [7], [8], [9]. There is currently no therapy for JE other than the treatment of symptoms [4]. Although improvements in agricultural practices and socioeconomic conditions have reduced the incidence of JE disease in some countries, for human vaccination against JE remains the most important and highly effective control measure.
IXIARO® is based on the attenuated JE virus strain SA14-14-2 propagated in Vero cells. In six completed Phase III studies, IXIARO® has been shown to be highly immunogenic with a safety and tolerability profile comparable to adjuvanted placebo [5]. Immunization with IXIARO® using a standard two-dose regimen provided a protective neutralizing JE antibody titre comparable to three doses of JE-VAX®, was also comparable using standard safety measures and showed an even better local tolerance profile [6].
IC51 was approved in early 2009 by the United States Food and Drug Administration and the European Medicines Agency, and recently by Health Canada under the trade name IXIARO® and by Australian Therapeutic Goods Administration under the trade name JESPECT®.
In endemic regions the most frequently affected age group is children, depending on the country children under 9 and 14 years [3], hence immunization should start early in childhood. JE vaccines like JE-VAX® or JenceVac™ are approved for paediatric use and administered to small children starting at the age of 1 year. In this article we fully present first immunogenicity and safety data from a study with IXIARO® administered to small children at two doses (3 and 6 μg) in comparison to JenceVac™, the standard JE vaccine in the geographic region were the study was performed [21].
Section snippets
Study design
This open-label randomized Phase II study was performed in one centre in Bangalore, India. The study was approved by the Ethical Review Board of the M.S. Ramaiah Medical College and Teaching Hospital, Bangalore, India. The Ethical Review Board consisted of ten members and operates in accordance with Good Clinical Practice (GCP) and other relevant guidelines. All procedures complied with local regulations. All parents or guardians of the children gave informed consent prior to exposure to
Participants and baseline characteristics
A total of 70 children were screened to randomize 60. All 60 children finished the study and only two children missed visits. For five children blood samples were not available and they were excluded from the PP efficacy analysis. Table 1 describes the demographic data of the three vaccine groups.
The three vaccine groups were comparable in their baseline demographic characteristics. Significantly more male children were enrolled in the study but the distribution was comparable between the
Discussion
In many Asian tropical and subtropical countries JE is a common viral encephalitis with some countries likely to see increased and some decreased rates of JE infections in the near future [12]. In endemic areas the fatality rate of JE infections is estimated to be about 10,000–15,000 cases per year [12]. Symptomatic JE infections have also been reported in Western countries in travellers to endemic areas [7], [8], [9]. The standard vaccination regimen of IXIARO® consists of two immunizations
Acknowledgements
The authors wish to thank the study participants and their families and thank the following persons for their contributions to this study: Christian Gartner, Susanne Eder, Dr. Rakesh Sinha and Mr. Srikanth T.
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