Clinical evaluation to confirm the manufacturing consistency of three lots of an adjuvanted glycoprotein D genital herpes vaccine in healthy seronegative pre-teen and adolescent girls: A phase III multi-center double-blind randomized trial

ObjectiveTo evaluate the consistency of three commercial scale lots of candidate herpes simplex virus (HSV) type 2 (HSV-2) vaccine in adolescent girls.MethodsA total of 554 healthy girls aged 10–17 years, from Belgium, Canada, and United States, were enrolled and randomized to receive one of the three manufacturing lots of the candidate glycoprotein D2 vaccine (gD2-AS04, GlaxoSmithKline Vaccines) according to a 0, 1 and 6-month schedule. Consistency was based on anti-gD geometric mean titers (GMTs) 1 month post-dose 3 among HSV seronegative subjects complying to study procedures (N = 312): two-sided 90% confidence interval (CI) for the GMT ratio between each pair of vaccine lots had to be within the [0.67; 1.5] consistency interval.ResultsPre-specified consistency criteria were reached. At month 2 (1 month after the second vaccine dose) anti-gD antibodies were detected in all study participants, while the proportion of subjects with HSV-2 neutralizing antibodies ranged from 93% to 96.2%, remaining >90% throughout the study (between 93.7% and 96.1% for the three vaccine lot groups at month 12). The three vaccine lots had similar reactogenicity profiles. The incidence of grade 3 solicited or unsolicited adverse events (AEs) ranged from 17.9% to 22.2% of subjects.ConclusionsThis study demonstrated the lot-to-lot consistency of three commercial scale production lots of herpes simplex candidate vaccine. The vaccine was immunogenic and had a clinically acceptable safety profile when administered in HSV type 1 and HSV-2 seronegative girls aged 10–17 years. The study was registered at clinicaltrials.gov (identifier NCT00224471).