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Post hoc analysis of reactogenicity trends between dose 1 and dose 2 of the adjuvanted recombinant zoster vaccine in two parallel randomized trials.

ABSTRACT: In two large clinical trials (ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]), two doses of the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster in adults ≥50 years of age. Solicited adverse events (AEs) were collected for 7 days post-each dose in a study sub-cohort. The incidence of reported solicited AEs was higher for RZV compared to placebo recipients. Since reactogenicity may contribute to a person's willingness to be vaccinated, knowing about expected reactogenicity might help keep high compliance with the second dose. This post hoc analysis assessed the intensity of solicited AEs post-dose 2 reported to the same event's intensity post-dose 1. Intensity was graded from 0 to 3, grade 3 indicating the highest severity. Of the vaccinees who did not experience a specific AE post-dose 1, 72.6-91.7% did not experience the same event after dose 2. Although the frequency of grade 3 AEs post-dose 2 was the highest in participants reporting the same AEs at grade 3 post-dose 1, 65.8-89.3% of vaccinees with grade 3 specific AEs post-dose 1 reported the same AEs at lower intensity post-dose 2. These data can help inform health-care professionals about the frequency and intensity of AEs post-dose 2 with respect to post-dose 1.

SUBMITTER: Colindres R

PROVIDER: S-EPMC7733973 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Post hoc analysis of reactogenicity trends between dose 1 and dose 2 of the adjuvanted recombinant zoster vaccine in two parallel randomized trials.

Colindres Romulo R Wascotte Valentine V Brecx Alain A Clarke Christopher C Hervé Caroline C Kim Joon Hyung JH Levin Myron J MJ Oostvogels Lidia L Zahaf Toufik T Schuind Anne A Cunningham Anthony L AL

Human vaccines & immunotherapeutics 20200429 11

In two large clinical trials (ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]), two doses of the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster in adults ≥50 years of age. Solicited adverse events (AEs) were collected for 7 days post-each dose in a study sub-cohort. The incidence of reported solicited AEs was higher for RZV compared to placebo recipients. Since reactogenicity may contribute to a person's willingness to be vaccinated, knowing about expe ...[more]

PMID: 32347767

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Project description:Abstract Background In the pivotal clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) showed high efficacy against herpes zoster and postherpetic neuralgia. The incidence of reported solicited events was higher in RZV compared with placebo recipients. Methods In these phase III, observer-blind, placebo-controlled trials conducted in 18 countries, adults ≥50 years of age (YOA, ZOE-50) and ≥70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Injection-site and general events were solicited for 7 days after each dose via diary cards in a participant subset. For this post-hoc analysis, ZOE-50 and ZOE-70 data from participants having completed the diary cards for both RZV doses were pooled. The intensity of each solicited event after dose 2 was stratified by the intensity of the same event after dose 1. Results Solicited injection-site and general events were recorded for both RZV doses by 4,676 and 4,668 vaccinees, respectively (Figure 1). Of 1,235 vaccinees with no injection-site event at dose 1, 881 (71.3%) reported no injection-site event and 20 (1.6%) reported a grade 3 event after dose 2. A total of 433 (9.3%) vaccinees reported a grade 3 injection-site event, either after dose 1 or dose 2. Of 244 vaccinees with grade 3 injection-site events at dose 1, 79 (32.4%) also reported a grade 3 event after dose 2. Of 2,312 vaccinees with no general event at dose 1, 1,617 (69.9%) reported no general event and 67 (2.9%) reported a grade 3 event after dose 2. A total of 499 (10.7%) vaccinees reported a grade 3 general event, either after dose 1 or dose 2. Of 222 vaccinees with grade 3 general events at dose 1, 81 (36.5%) also reported a grade 3 general event after dose 2. In general, vaccinees who did not experience a certain event after dose 1, did not experience this event after dose 2 either. Most vaccinees reporting a specific event at high intensity after dose 1, reported the same event at a lower intensity (or not at all) after dose 2 (Figures 2 and 3). Conclusion While not powered to predict event intensity of the second RZV dose, our data provides an overview of event intensity after RZV dose 2 according to the intensity of the same event experienced after dose 1. Funding: GlaxoSmithKline Biologicals SA. Disclosures All authors: No reported disclosures.

Project description:Abstract Background The risk of herpes zoster (HZ) has been reported to vary by sex and ethnicity. In 2 large-scale clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) demonstrated high vaccine efficacy (VE) against HZ and post-herpetic neuralgia (PHN). We present a post-hoc analysis of RZV efficacy against HZ and PHN in the ZOE-50/70 population stratified by sex, geographic region and geographic ancestry/ethnicity. Methods The ZOE-50 and ZOE-70 studies were phase III, observer-blind, placebo-controlled trials conducted across 5 geographic regions. Adults ≥ 50 years of age (YOA; ZOE-50) and ≥ 70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Here, VE against HZ by sub-population was estimated from the ZOE-50 population (≥ 50 YOA) and the pooled ZOE-50/70 population (pooled ≥ 70 YOA), and VE against PHN by sub-population was evaluated in the pooled ≥ 70 YOA. Results VE was evaluated in 7,340 RZV and 7,413 placebo recipients ≥ 50 YOA (mean age: 62.3 [RZV], 62.2 [placebo] YOA) and 8,250 RZV and 8,346 placebo recipients in pooled ≥ 70 YOA (mean age: 75.5 [RZV, placebo] YOA). VE against HZ and PHN was similar for women and men in the ≥ 50 YOA and pooled ≥ 70 YOA (Tables 1 and 2). Point estimates for VE against HZ by geographic region ranged from 95.7% to 97.2% in ≥ 50 YOA and from 87.3% to 95.1% in pooled ≥ 70 YOA (Table 1). Point estimates for VE against PHN by geographic region ranged from 86.8% to 100% in pooled ≥ 70 YOA. VE was similar across geographic ancestry groups in pooled ≥ 70 YOA: VE point estimates against HZ ranged from 89.6% to 100% and VE against PHN ranged from 87.5% to 100% (Tables 1 and 2). VE against HZ was 88.1% and against PHN was 65.9% in Hispanic participants in pooled ≥ 70 YOA (Tables 1 and 2). Conclusion Acknowledging the limitations including the post-hoc character of these analyses and the small number of participants and cases available, our data suggest that RZV is efficacious against HZ and PHN irrespective of sex, geographic region, geographic ancestry, and ethnicity. Funding: GlaxoSmithKline Biologicals SA. Disclosures All authors: No reported disclosures.

Project description:Abstract Background Patients with hematologic malignancies treated with anticancer immunosuppressive therapies (ITs) are at increased risk of herpes zoster (HZ). In a previous report of this phase 3, observer-blind, multicenter trial (NCT01767467), the adjuvanted recombinant zoster vaccine (RZV) was shown to be immunogenic and well-tolerated in ≥18 years of age patients with hematologic malignancies who completed or were undergoing anticancer IT.1 Here we report end-of-study results from the same trial. Methods Participants were randomized 1:1 to receive 2 doses of RZV or placebo (PL) 1–2 months apart, either ≥10 days before or after a cancer therapy cycle, or 10 days to 6 months after cancer therapy ended. Humoral and cell-mediated immune (CMI) responses were evaluated at 1 month and 12 months post-dose 2 (month 2 and month 13, respectively). Confirmatory objectives were to evaluate humoral response rate to RZV and to compare humoral immune responses to RZV and PL at month 2 excluding either subjects with chronic lymphocytic leukemia and non-Hodgkin B-cell lymphoma (NHBCL), or only those with NHBCL. Efficacy against HZ was explored in a post-hoc analysis of confirmed HZ cases. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were recorded throughout the study. Results Of the 562 (RZV: 283, PL: 279) treated participants, 415 (RZV: 217, PL: 198)/310 (RZV: 168, PL: 142) were included in the according-to-protocol (ATP) cohort for humoral immunogenicity/immune persistence. The ATP sub-cohort for CMI included 132 (RZV: 69, PL: 63) participants at month 2 and 100 (RZV: 54, PL: 46) at month 13. All confirmatory immunogenicity objectives were met (Table 1). RZV efficacy against HZ, assessed post-hoc, was 87.2% (Table 2). RZV was more reactogenic than PL. The occurrence of unsolicited AEs, SAEs, and pIMDs was similar between the study groups (Table 3). Conclusion RZV induced robust humoral and cellular immune responses and showed an effect in the reduction of HZ incidence in patients with hematologic malignancies who completed or were undergoing anticancer IT. No safety concerns were identified. Reference 1. Oostvogels et al. IDWeek2017, abs 1344. Funding. GlaxoSmithKline Biologicals SA. Disclosures A. F. Dagnew, GSK: Employee and Shareholder, Salary. J. Murphy, GSK: Investigator, Research support. S. A. McNeil, GSK group of companies: Grant Investigator, Research grant and Research support. B. Salaun, GSK group of companies: Employee and Shareholder, Salary. E. Di Paolo, GSK group of companies: Employee, Salary. L. Campora, GSK group of companies: Employee and Shareholder, Salary. M. López-Fauqued, GSK group of companies: Employee, Salary. M. El Idrissi, GSK group of companies: Employee, Salary. A. Schuind, GSK: Employee, Salary. T. C. Heineman, GSK group of companies: Consultant, Employee and Shareholder, Consulting fee and Salary. P. Van Den Steen, GSK: Employee and Shareholder, Restricted shares and Salary. L. Oostvogels, GSK: Employee, Salary and Stock and stock options.

Project description:IntroductionThe adjuvanted recombinant zoster vaccine (RZV) has demonstrated high efficacy against herpes zoster in older adults and immunocompromised populations. We present comprehensive safety data from six clinical trials in immunocompromised populations (autologous hematopoietic stem cell transplant and renal transplant recipients, patients with hematologic malignancies, patients with solid tumors, and human immunodeficiency virus-infected adults) who are at an increased risk of herpes zoster.MethodsIn all trials, immunocompromised adults ≥ 18 years of age were administered RZV or placebo. Safety was evaluated in the total vaccinated cohort. Solicited adverse events (AEs) were collected for 7 days and unsolicited AEs for 30 days after each dose. Serious AEs, fatal serious AEs, and potential immune-mediated diseases were collected from dose 1 until 12 months post-last dose or study end. Data were pooled for solicited AEs; unsolicited AEs, (fatal) serious AEs, and potential immune-mediated diseases were analyzed for each individual trial. All AEs were analyzed for sub-strata of adults 18-49 years of age and ≥ 50 years of age.ResultsIn total, 1587 (RZV) and 1529 (placebo) adults were included in the pooled total vaccinated cohort. Solicited AEs were more common after RZV than placebo, were generally more common in the younger age stratum, and were mostly mild to moderate and resolved within 3 days (median duration). Unsolicited AEs and serious AEs were in line with underlying diseases and therapies. Across studies, the percentage of adults reporting one or more unsolicited AE was comparable between RZV and placebo, irrespective of age stratum. The percentage of adults reporting one or more serious AE, fatal serious AE, or potential immune-mediated diseases was generally similar for RZV and placebo, irrespective of age stratum. Overall, no safety concerns were identified.ConclusionsRecombinant zoster vaccine has a clinically acceptable safety profile. With the previously published vaccine efficacy and immunogenicity results, these data support a favorable benefit-risk profile of RZV vaccination in immunocompromised populations who are at an increased risk of herpes zoster.

Dataset Information

Post hoc analysis of reactogenicity trends between dose 1 and dose 2 of the adjuvanted recombinant zoster vaccine in two parallel randomized trials.

Publications

Post hoc analysis of reactogenicity trends between dose 1 and dose 2 of the adjuvanted recombinant zoster vaccine in two parallel randomized trials.

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