Results of a Safety Pooled Analysis of an Adjuvanted Herpes Zoster Subunit Vaccine in More than 14,500 Participants Aged 50 Years or Older
Bibliographic record
Abstract
Abstract Background The recombinant herpes zoster (HZ) subunit vaccine (HZ/su) has shown efficacy against HZ in adults ≥50 and ≥70 years of age (YOA), in two pivotal Phase III clinical trials (NCT01165177, NCT01165229). A pooled safety analysis of data from these two efficacy studies was performed, including a comparative analysis on HZ/su vs. placebo groups, to provide a comprehensive understanding of the HZ/su safety profile. Methods Two pivotal, randomized, placebo-controlled Phase III studies, assessed the efficacy, reactogenicity and safety of HZ/su, administered intramuscularly according to a 0, 2-month schedule. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each dose, respectively; serious AEs (SAEs) for 1 year after last dose; fatal and related SAEs and potential immune-mediated diseases (pIMDs) during the entire study period. Reactogenicity was assessed in a subset of participants; safety was assessed in all vaccinated participants. Results 29,305 participants ≥50 YOA (HZ/su: 14,645; placebo: 14,660) were included in the pooled analysis. HZ/su was more reactogenic than placebo. Local reactions were mostly mild to moderate in intensity and transient (median duration = 3 days); the percentages of participants reporting SAEs, fatal SAEs and pIMDs were similar in both groups, at 30 days and 1 year after last dose (Figures 1 and 2). Percentages of fatal SAEs ranged between 4.3% (95% Confidence Interval [CI]: 4.0–4.7) and 4.6% (95% CI: 4.3–5.0) and pIMDs between 1.2% (95% CI: 1.1–1.4) and 1.4% (95% CI: 1.2–1.6), in HZ/su and placebo groups, respectively. In both groups, the most frequent causes of death were neoplasms, cardiac disorders, and respiratory tract infections and infestations, and most frequent pIMDs were polymyalgia rheumatica, rheumatoid arthritis and psoriasis. Conclusion No safety concern was identified. Together with the high efficacy against HZ (97.2% [95% CI: 93.7–99.0],1 91.3% [95% CI: 86.8–94.5]2), the safety data supports a favorable benefit/risk profile of HZ/su in participants ≥50 YOA. Funding GlaxoSmithKline Biologicals SA Disclosures M. López-Fauqued, GSK Biologicals’: Employee, Salary; L. Campora, GSK Biologicals’: Employee, Salary; F. Delannois, GSK Vaccines: Employee, Salary; M. El Idrissi, GSK Vaccines: Employee, Salary; E. Ledent, GSK Vaccines: Employee, Salary; J. Diez-Domingo, GSK Vaccines: Consultant and Investigator, Educational support and Research grant; J. McElhaney, GSK Vaccines: Scientific Advisor, Speaker honorarium; S. McNeil, GSK/Merck: Grant Investigator, Investigator and Scientific Advisor, Consulting fee, Grant recipient, Research grant, Research support and Speaker honorarium; F. De Looze, GSK Vaccines: Investigator and Research Contractor, Research support; F. Tavares Da Silva, GSK Vaccines: Employee, restricted shares and Salary
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.034 | 0.034 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.020 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".