fficacy , safety and immunogenicity of a human rotavirus vaccine ( RIX 4414 ) in ong Kong children up to three years of age : A randomized , controlled trial

Background: A phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (RotarixTM) against severe rotavirus gastroenteritis in children up to three years of age. Methods: Healthy infants aged 6–12 weeks were enrolled between 08-December-2003 and 31-August2005 and received two oral doses of either RIX4414 vaccine (N = 1513) or placebo (N = 1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two eywords: fficacy astroenteritis and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1–2 months post-Dose 2 using ELISA (cut-off = 20 U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period. ong Kong ntussusception otavirus afety Results: In children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%–99.9%) and 96.1% (95% CI: 76.5%–99.9%), respectively. The seroconversion rate 1–2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%–99.9%). Abbreviations: ARSN, Asian Rotavirus Surveillance Network; ATP, According-to-protocol; CCID50, Cell culture infectious dose; DTPa, Diphtheria-tetanus-acellular pertussis; TPw, Diphtheria-tetanus-whole cell pertussis; ELISA, Enzyme-linked immunosorbent assay; GMCs, Geometric mean concentrations; Hib, Haemophilus influenzae type b; CD, International Classification of Diseases; IPV, Inactivated polio vaccine; OPV, Oral polio vaccine; RT-PCR, Reverse transcriptase polymerase chain reaction; RVGE, Rotavirus astroenteritis; SAE, Serious adverse event; U/mL, Units per milliliter; WHO, World Health Organization. ∗ Corresponding author at: Department of Paediatrics, The Chinese University of Hong Kong Prince of Wales Hospital, Shatin, Hong Kong, China. el. : +852 26322861; fax: +852 26360020. E-mail addresses: lauylung@hku.hk (Y.-L. Lau), tony-nelson@cuhk.edu. hk (E.A.S. Nelson), pkh978@ha.org.hk (K.-H. Poon), paulkschan@cuhk.edu. hk (P.K.S. Chan), sschiu@hkucc.hku.hk (S. Chiu), yntzsung@cuhk.edu. hk (R. Sung), leungcw@ha.org.hk (C.W. Leung), dkkng@ha.org.hk (D. Ng), maskmanma@yahoo.com (Y.M. Ma), w.chan@mail.stpaul. org.hk (D. Chan), leetl@hkucc.hku.hk (T.L. Lee), joycesf.tang@ucn.org.hk (J. Tang), kwanyw1@ha.org.hk (Y.W. Kwan), patipls@gmail.com (P. Ip), 8914760@graduate.hku.hk (M. Ho), eva fung@cuhk.edu. hk (L.-W.E. Fung), haiwen.h. tang@gsk.com (H. Tang), p.v. suryakiran@gsk.com (P.V. Suryakiran), htay.h. han@gsk.com H.H. Han), halubo@yahoo.com (H. Bock). 1 Principal Investigator, The University of Hong Kong. 2 Principal Investigator, The Chinese University of Hong Kong. 264-410X © 2013 Elsevier Ltd. ttp://dx.doi. org/10.1016/j.vaccine. 2013.03. 001 Open access under CC BY-NC-ND license. 2254 Y. -L. Lau et al. / Vaccine 31 (2013) 2253– 2259 At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value = 0.130). Six intussusception cases were reported (RIX4414 = 4; placebo = 2) and none was assessed to be vaccine-related. Conclusion: RIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children.