Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in Japanese healthy adults: A Phase I study.

V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) to address the burden of residual adult pneumococcal disease after the introduction of pediatric PCVs into national immunization programs (NIPs) and includes serotypes highly prevalent in adult invasive pneumococcal disease (IPD). This Phase I study assessed the safety, tolerability, and immunogenicity of V116 in Japanese adults. Participants ≥20 years of age were randomized to receive a single dose of V116 or 23-valent pneumococcal polysaccharide vaccine (PPSV23) at day 1. Outcomes were solicited injection-site and systemic adverse events (AEs) from day 1 to day 5, vaccine-related serious AEs from day 1 through day 30, and serotype-specific opsonophagocytic antibody (OPA) titers and immunoglobulin G (IgG) concentrations at day 30. Overall, 102 participants were randomized 1:1 to each group. Comparable proportions vaccinated with V116 and PPSV23 experienced ≥1 solicited injection-site AE and ≥1 solicited systemic AE. The most common injection-site AEs were injection-site pain (V116: 54.9%; PPSV23: 66.7%) and swelling (V116 and PPSV23: 13.7%), and the most common systemic AEs were myalgia (V116: 17.6%; PPSV23: 19.6%) and fatigue (V116: 13.7%; PPSV23: 9.8%). Solicited AEs were mostly mild and of ≤3 days duration. No vaccine-related serious AEs or deaths were reported. The OPA and IgG findings showed that the immunogenicity of V116 and PPSV23 were comparable for the 12 common serotypes and V116 was more immunogenic for the nine unique serotypes compared with PPSV23. V116 was well tolerated, with a safety profile similar to PPSV23, and induced functional antibodies against all 21 serotypes.

Safety and Immunogenicity of V114, a 15-valent Pneumococcal Conjugate Vaccine, Compared with 13-valent Pneumococcal Conjugate Vaccine in Japanese Adults Aged ≥65 Years: Subgroup Analysis of a Randomized Phase III Trial (PNEU-AGE).

The safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), were assessed in a pivotal phase III trial conducted in healthy adults ≥50 years of age (NCT03950622, Japic-CTI 194845). We performed a subgroup analysis of 245 Japanese participants (all ≥65 years of age). The participants were randomized 1:1 to receive a single dose of V114 or 13-valent PCV (PCV13). Immune responses were evaluated at baseline and at 30 days post-vaccination. Non-serious and serious adverse events (AEs) were evaluated at 14 days and 6 months after vaccination, respectively. The proportions of participants experiencing solicited and serious AEs were comparable for both vaccines, and all solicited AEs were mild or moderate in severity. Geometric mean titers of serotype-specific opsonophagocytic activity (OPA) at 30 days post-vaccination were comparable between groups for all 13 shared serotypes and were higher with V114 for the unique serotypes 22F and 33F. The proportion of participants with a ≥4-fold increase in serotype-specific OPA responses from pre-vaccination to 30 days post-vaccination was higher for V114 than for PCV13 for serotypes 3, 22F, and 33F. V114 was well tolerated and immunogenic in Japanese adults ≥65 years of age, showing safety and immunogenicity profiles consistent with those seen in the overall study population.

Patient-reported outcomes in individuals with hepatitis C virus infection treated with elbasvir/grazoprevir.

PURPOSE: People chronically infected with hepatitis C virus (HCV) have diminished patient-reported outcomes (PROs). This study aimed to compare the impact of elbasvir/grazoprevir (EBR/GZR) treatment versus sofosbuvir with pegylated interferon and ribavirin (SOF/PR) on changes in PROs: 1) during the treatment period and 2) at posttreatment follow-up. PATIENTS AND METHODS: PRO data collected during the Phase III C-EDGE Head-2-Head (H2H) open-label study was analyzed. In this trial, patients infected with HCV were randomized 1:1 to receive either EBR/GZR or SOF/PR for 12 weeks. Patients self-administered the Short Form-36 version 2 (SF-36v2®) Health Survey Acute (1-week recall) Form and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at baseline, during treatment, and posttreatment. Between-group differences in mean change of PRO scores from baseline were estimated during the treatment period and also at the posttreatment follow-up. Effect sizes were calculated to evaluate if the detected change in mean PRO scores is clinically meaningful between groups. RESULTS: There were 255 patients (99.2% White, 54.1% female, 74.9% treatment naïve) included in the analysis. During the treatment period, significant declines in SF-36v2 scores were observed across all domains for the SOF/PR group. Compared to the SOF/PR group, the EBR/GZR group reported more improvement in scores across all SF-36v2 domain scores at the end of the treatment period. At treatment week 12, the between-group differences for 6 out of the 8 domain scores for these patients reflected at least moderate effects (effect sizes >0.5). No significant between-group differences in change in SF-36v2 scores from baseline were detected posttreatment. The decline in SF-36v2 scores observed during the treatment period for the SOF/PR group returned to near baseline scores or above posttreatment. Treatment with EBR/GZR did not impact fatigue scores, but treatment with SOF/PR led to increased fatigue scores during treatment which resolved by posttreatment follow-up week 12. CONCLUSION: This study demonstrated that HCV treatment with EBR/GZR resulted in a significantly better PRO profile as compared to SOF/PR. PROs are an important consideration as worsening PROs experienced during treatment may negatively influence adherence and ultimately contribute to an unfavorable clinical outcome. CLINICALTRIALSGOV IDENTIFIER: NCT02358044.