PMID- 30732648 OWN - NLM STAT- MEDLINE DCOM- 20200220 LR - 20200309 IS - 1471-2431 (Electronic) IS - 1471-2431 (Linking) VI - 19 IP - 1 DP - 2019 Feb 7 TI - Safety and immunogenicity of a varicella vaccine without human serum albumin (HSA) versus a HSA-containing formulation administered in the second year of life: a phase III, double-blind, randomized study. PG - 50 LID - 10.1186/s12887-019-1425-7 [doi] LID - 50 AB - BACKGROUND: A new formulation of the live-attenuated varicella vaccine Varilrix (GSK) produced without human serum albumin (HSA) was developed to minimize a theoretical risk of transmission of infectious diseases. A previous study showed that the vaccine was immunologically non-inferior to the HSA-containing vaccine and well-tolerated in toddlers; low-grade fever was numerically higher in children receiving the vaccine without HSA, but the study lacked power to conclude on this difference. METHODS: In this phase III, double-blind, multi-center study, healthy 12-23-month-olds were randomized (1:1) to receive two doses of the varicella vaccine without (Var-HSA group) or with HSA (Var + HSA group) at days 0 and 42. The primary objective compared safety of the vaccines in terms of incidence of fever > 39.0 degrees C in the 15-day period post-first vaccination. The objective was considered met if the upper limit of the 95% confidence interval for the between-group difference in the incidence of fever > 39.0 degrees C was /=1 vaccination. Fever > 39.0 degrees C was reported in 3.9 and 5.2% of participants in the Var-HSA and Var + HSA groups, with a between-group difference of - 1.29 (95% confidence interval: - 3.72-1.08); therefore, the primary objective was achieved. Fever rates post-each dose and the incidence of solicited local and general adverse events (AEs) were comparable between groups. Unsolicited AEs were reported for 43.9 and 36.5% of children in the Var-HSA group and 45.8 and 36.0% of children in the Var + HSA group, during 43 days post-dose 1 and 2, respectively. Serious AEs occurred in 2.1% (group Var-HSA) and 2.4% (group Var + HSA) of children, throughout the study. In a sub-cohort of 364 children, all had anti-varicella-zoster virus antibody concentrations >/=50 mIU/mL post-dose 2; comparable geometric mean concentrations were observed between the groups. CONCLUSIONS: The varicella vaccine formulated without HSA did not induce higher rates of fever during the 15 day-post-vaccination period, as compared with the original HSA-containing vaccine. The two vaccines displayed similar safety and immunogenicity profiles in toddlers. TRIAL REGISTRATION: NCT02570126 , registered on 5 October 2015 (www.clinicaltrials.gov). FAU - Faust, Saul N AU - Faust SN AD - NIHR Southampton Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK. s.faust@soton.ac.uk. FAU - Le Roy, Maguelone AU - Le Roy M AD - GSK, Avenue Fleming 20, B-1300, Wavre, Belgium. FAU - Pancharoen, Chitsanu AU - Pancharoen C AD - Department of Pediatrics and Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok, 10330, Thailand. FAU - Weber, Miguel Angel Rodriguez AU - Weber MAR AD - Instituto Nacional de Pediatria, Insurgentes Sur 3700C Col. Insurgentes Cuicuilco, Coyoacan, 04530, Mexico City, Mexico. FAU - Cathie, Katrina AU - Cathie K AD - NIHR Southampton Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK. FAU - Behre, Ulrich AU - Behre U AD - Private Practice, Hauptstrasse 240, 77694, Kehl, Germany. FAU - Bernatoniene, Jolanta AU - Bernatoniene J AD - Pediatric Infectious Disease Department, Education Centre Level 6, University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol, BS2 8AE, UK. FAU - Snape, Matthew D AU - Snape MD AD - Oxford Vaccine Group, Department of Pediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Headington, Oxford, OX3 9DU, UK. FAU - Helm, Klaus AU - Helm K AD - Private practice, Paulinenstrasse 71a, 32756, Detmold, Germany. FAU - Medina Pech, Carlos Eduardo AU - Medina Pech CE AD - Medical Care and Research SA de CV, Calle 32 No. 217 Col. Garcia Gineres, 97070, Merida, Yucatan, Mexico. FAU - Henry, Ouzama AU - Henry O AD - GSK, 14200 Shady Grove Rd, Rockville, MD, 20850, USA. FAU - Baccarini, Carmen AU - Baccarini C AD - GSK at the time of study conduct, 160 North Gulph Road, King of Prussia, PA, 19406, USA. FAU - Povey, Michael AU - Povey M AD - GSK, Avenue Fleming 20, B-1300, Wavre, Belgium. FAU - Gillard, Paul AU - Gillard P AD - GSK, Avenue Fleming 20, B-1300, Wavre, Belgium. LA - eng SI - ClinicalTrials.gov/NCT02570126 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190207 PL - England TA - BMC Pediatr JT - BMC pediatrics JID - 100967804 RN - 0 (Chickenpox Vaccine) RN - ZIF514RVZR (Serum Albumin, Human) SB - IM MH - Chickenpox/*prevention & control MH - Chickenpox Vaccine/adverse effects/*immunology MH - Double-Blind Method MH - Female MH - Humans MH - *Immunogenicity, Vaccine MH - Infant MH - Male MH - Serum Albumin, Human/*administration & dosage PMC - PMC6366055 OTO - NOTNLM OT - Human serum albumin OT - Non-inferiority OT - Safety OT - Varicella vaccine COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by independent ethics committees/institutional review boards at each site (University of Tartu, Office of Research and Development; Landesarztekammer Baden-Wurttemberg Medical Board; National Institute of Pediatrics, Coyoacan; Medical Care and Research, Merida; Faculty of Medicine, Chulalongkorn University; NHS, Health Research Authority, North West-Liverpool East Research Ethics Committee) and conducted in accordance with provisions of the Declaration of Helsinki. Written informed consent was obtained from all children's parents prior to enrolment in the study. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: MLR, OH, CB, MP and PG are employees of the GSK group of companies, and OH and PG hold shares in the GSK group of companies as part of their employee remuneration. CB was employed by the GSK group of companies during the conduct of this study and is a current employee of Sanofi Pasteur. She holds shares in the GSK group of companies and Sanofi Pasteur. SNF declares that his institution received grants from the GSK group of companies for the conduct of this trial. SNF also declares support through his institution for the conduct of other trials (from the GSK group of companies, Sanofi-Pasteur, Pfizer, AstraZeneca, MedImmune, Alios, Ablynx and Merck). SNF declares that his institution received other support from Pfizer, AstraZeneca, MedImmune, Sanofi, Sequerius and Merck for advisory board participation. MDS declares that his institution received grants from the GSK group of companies for the conduct of this trial. MDS also declares support through his institution for the conduct of other trials (from the GSK group of companies, Sanofi-Pasteur, Pfizer, MedImmune, Novavax and Johnson and Johnson). CP, MA RW, KC, UB, JB, KH and CE MP have indicated they have no financial relationship or conflict of interest relevant to this article to disclose. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/02/09 06:00 MHDA- 2020/02/23 06:00 PMCR- 2019/02/07 CRDT- 2019/02/09 06:00 PHST- 2018/10/24 00:00 [received] PHST- 2019/01/31 00:00 [accepted] PHST- 2019/02/09 06:00 [entrez] PHST- 2019/02/09 06:00 [pubmed] PHST- 2020/02/23 06:00 [medline] PHST- 2019/02/07 00:00 [pmc-release] AID - 10.1186/s12887-019-1425-7 [pii] AID - 1425 [pii] AID - 10.1186/s12887-019-1425-7 [doi] PST - epublish SO - BMC Pediatr. 2019 Feb 7;19(1):50. doi: 10.1186/s12887-019-1425-7.