Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) antibody responses to the 9-valent abstract human papillomavirus (9vHPV) vaccine among girls and boys (aged 9–14 years) receiving 2- dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16–26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36. METHODS: Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36. RESULTS: Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%–100%; IgG-LIA: 91%–100%) and young women who received 3 doses (cLIA: 78%–98%; IgG-LIA: 91%–100%) remained seropositive 2 to 2.5 years after the last regimen dose. CONCLUSIONS: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.Medicin

Evaluation of immunogenicity and safety of VARIVAX™ New Seed Process (NSP) in children

Prior to availability of an effective vaccine, an estimated 4 million cases of varicella occurred annually in the United States, resulting in 10,000 hospitalizations and over 100 deaths. With the increased usage of a two-dose varicella vaccine (as recommended by the ACIP), approval of other VZV-containing products and the adoption of varicella vaccination in additional countries, the demand for VZV-containing vaccines has increased. This study (NCT02062502) evaluated the safety, tolerability, and immunogenicity of VARIVAX™ (VAR, varicella vaccine live) manufactured using a new seed manufacturing process (VARNSP) compared to the currently licensed VAR. Healthy children 12–23 months were randomized (1:1) into Group 1 (2 doses of VARNSP given concomitantly with M-M-R™ II, ∼3 months apart) versus  Group 2 (2 doses of VAR given concomitantly with M-M-R™ II, ∼3 months apart).  Serum samples collected prior to vaccination on Day 1 and 6 weeks Postdose 1 were tested for antibody to VZV using a glycoprotein enzyme-linked immunosorbent assay (gpELISA).  Safety was assessed Days 1 to 42 following each vaccination. Six weeks Postdose 1, the response rate (percent of subjects with VZV antibody titer ≥5 gpELISA units/mL) of VARNSP was non-inferior compared to VAR.  Vaccine-related adverse events (AEs) were comparable with the exception of measles-like rash, where a greater number of rashes were observed with VAR than VARNSP.  The 2 vaccination groups were comparable with incidence rates of AEs, injection-site AEs, vaccine-related AEs, systemic AEs, and serious AEs. This new process is an important innovation for the extreme demand of sustaining sufficient supplies of varicella vaccine to protect our communities against diseases caused by VZV

Development of a novel observer-reported outcome measure for the assessment of Respiratory Syncytial Virus (RSV) infection symptoms in pediatric clinical trials

Abstract Background Respiratory syncytial virus (RSV) is a seasonal infection affecting most children by 2 years of age and the leading cause of lower respiratory tract infection requiring hospitalization in infants. Novel antiviral medications are in development to improve the clinical outcomes of RSV; however, no clinical outcome assessments (COAs) for RSV have been developed in alignment with the United States Food and Drug Administration patient-reported outcome guidance to assist in the evaluation of new therapies. To address this need, an observer-reported outcome (ObsRO) measure designed to assess observable RSV symptoms was created. Methods The literature was reviewed to evaluate existing COAs and identify constructs of interest. Individual caregiver interviews elicited concepts that informed item development, and candidate items were subsequently evaluated in two rounds of cognitive testing. Separate cohorts of caregivers of RSV-infected nonhospitalized and hospitalized infants participated. Therapeutic-area experts provided input throughout the instrument development process. Results Caregivers of 39 children < 24 months old with RSV (31 nonhospitalized, 8 hospitalized) participated in in-depth, individual interviews during concept elicitation and cognitive debriefing, resulting in 21 concepts identified as potentially observable and relevant to young children with RSV. The item pool was reduced to 12 cardinal symptoms and behavior impacts reported to be directly observable by caregivers, with 10 daytime and 9 nighttime symptoms to capture diurnal variation in severity. Conclusions The RSV Caregiver Diary assesses RSV symptom severity and change from the parent or caregiver perspective in a standardized manner to measure treatment benefit. Following psychometric evaluation and refinement, this tool is expected to be suitable for assisting in the clinical development of RSV therapeutics

Psychometric evaluation of a caregiver diary for the assessment of symptoms of respiratory syncytial virus

Abstract Background There are no clinical outcome assessment (COA) tools developed in accordance with Food and Drug Administration (FDA) guidance suitable for the evaluation of symptoms associated with respiratory syncytial virus (RSV) infection among infants. The Gilead RSV Caregiver Diary (GRCD) is being developed to fulfill this need; the present research evaluates the GRCD and documents its reliability, validity, and responsiveness among children < 24 months of age with acute RSV infection. Methods A prospective, observational study was conducted in the United States during the 2014–2015 northern hemisphere winter season. Subjects were < 24-month, full-term, previously healthy infants with confirmed RSV infection and ≤5 days of symptoms. The GRCD was completed twice daily for 14 days by caregivers. Additional data were collected during the initial visit, subsequent visits, and end-of-study interview. Test-retest reliability (kappa and intraclass correlation coefficients [ICCs]), construct validity (correlations and factor analyses), discriminating ability (analyses of variance and chi-square), and responsiveness (effect sizes and standardized response means) were evaluated. Results A total of 103 subjects were enrolled (mean age 7.4 ± 5.3 months). GRCD items were grouped into different subscales according to question content, which, with the exception of the behavior impact domain (ICC = 0.43), demonstrated internal consistency (alphas = 0.78–0.94) and test-retest reliability (ICCs = 0.77–0.94). Hypothesized correlations with parent global ratings of RSV severity ranged from 0.45 to 0.70 and provided support for construct validity. Support for discriminating ability was limited. Effect sizes ranged from − 1.48 to − 4.40, indicating the GRCD was responsive to change. Conclusions These psychometric analyses support the validity, reliability, and responsiveness of the GRCD for assessing RSV symptoms in children < 24 months of age

Additional file 1: of Development of a novel observer-reported outcome measure for the assessment of Respiratory Syncytial Virus (RSV) infection symptoms in pediatric clinical trials

Full Study Inclusion/Exclusion Criteria. (DOCX 19 kb

Additional file 2: of Development of a novel observer-reported outcome measure for the assessment of Respiratory Syncytial Virus (RSV) infection symptoms in pediatric clinical trials

Abbreviated Item Tracking Matrix. (DOCX 18 kb

Additional file 1: of Psychometric evaluation of a caregiver diary for the assessment of symptoms of respiratory syncytial virus

Table S1. Inclusion/Exclusion Criteria for the GRCD Validation Study, Table S2 Schedule of Key Events for the GRCD Validation Study. (DOCX 17 kb