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Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial

BACKGROUND: Hematologic malignancy (HM) patients receiving immunosuppressive cancer therapy (ICT) are at increased risk of herpes zoster (HZ). Currently, no HZ vaccine is indicated for immunocompromised patients. The HZ subunit vaccine candidate (HZ/su), containing recombinant varicella zoster virus...

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Autor principal: Oostvogels, Lidia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5631126/
http://dx.doi.org/10.1093/ofid/ofx163.1040
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author Oostvogels, Lidia
author_facet Oostvogels, Lidia
author_sort Oostvogels, Lidia
collection PubMed
description BACKGROUND: Hematologic malignancy (HM) patients receiving immunosuppressive cancer therapy (ICT) are at increased risk of herpes zoster (HZ). Currently, no HZ vaccine is indicated for immunocompromised patients. The HZ subunit vaccine candidate (HZ/su), containing recombinant varicella zoster virus glycoprotein E and AS01(B) Adjuvant System, showed >90% efficacy and an acceptable safety profile in immunocompetent adults in all age groups ≥50 years. Here we report HZ/su immunogenicity and safety in HM adults ≥18 years of age who completed or are undergoing ICT. METHODS: In this phase III, observer-blind, multicenter study (NCT01767467), participants were randomized 1:1 to receive HZ/su or placebo (2 doses, 1–2 months apart) ≥10 days pre- or post-ICT. Humoral and cell-mediated immunogenicity (CMI) were assessed. The co-primary immunogenicity objectives were to evaluate HZ/su vaccine response rate and compare the immune response to HZ/su and placebo in participants excluding those with non-Hodgkin B-cell lymphoma (NHBCL) or chronic lymphocytic leukemia (CLL) at 1 month post-dose 2 (M2). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Serious AEs (SAEs), disease-related events and potential immune-mediated diseases (pIMDs) were recorded throughout the study. Partial safety results up to 6 months post-dose 2 are shown (partially blinded, ongoing study). RESULTS: Of 562 participants (283 HZ/su 283; placebo 279), (mean age 57.3 [HZ/su 56.8; placebo 57.8] years), 415 were included in the according-to-protocol (ATP) cohort for humoral immunogenicity and 132 in the ATP sub-cohort for CMI. M2 immune responses were higher in the HZ/su group (Table 1). Both co-primary immunogenicity objectives were met (Figure 1). The most frequent local and general solicited AEs were pain and fatigue, reported by 48.2% and 47.8% of all participants (per-group data remain blinded). The frequency of unsolicited AEs, SAEs and pIMDs in the 2 groups was similar (Table 2). CONCLUSION: HZ/su induced robust humoral and cellular immune responses at M2 in HM adults excluding NHBCL and CLL, who completed or are undergoing ICT. No safety concerns were observed up to 6 months post-dose 2. FUNDING: GlaxoSmithKline Biologicals SA DISCLOSURES: L. Oostvogels, GSK group of companies: Employee and Shareholder, Salary and Shares
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spelling pubmed-56311262017-11-07 Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial Oostvogels, Lidia Open Forum Infect Dis Abstracts BACKGROUND: Hematologic malignancy (HM) patients receiving immunosuppressive cancer therapy (ICT) are at increased risk of herpes zoster (HZ). Currently, no HZ vaccine is indicated for immunocompromised patients. The HZ subunit vaccine candidate (HZ/su), containing recombinant varicella zoster virus glycoprotein E and AS01(B) Adjuvant System, showed >90% efficacy and an acceptable safety profile in immunocompetent adults in all age groups ≥50 years. Here we report HZ/su immunogenicity and safety in HM adults ≥18 years of age who completed or are undergoing ICT. METHODS: In this phase III, observer-blind, multicenter study (NCT01767467), participants were randomized 1:1 to receive HZ/su or placebo (2 doses, 1–2 months apart) ≥10 days pre- or post-ICT. Humoral and cell-mediated immunogenicity (CMI) were assessed. The co-primary immunogenicity objectives were to evaluate HZ/su vaccine response rate and compare the immune response to HZ/su and placebo in participants excluding those with non-Hodgkin B-cell lymphoma (NHBCL) or chronic lymphocytic leukemia (CLL) at 1 month post-dose 2 (M2). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Serious AEs (SAEs), disease-related events and potential immune-mediated diseases (pIMDs) were recorded throughout the study. Partial safety results up to 6 months post-dose 2 are shown (partially blinded, ongoing study). RESULTS: Of 562 participants (283 HZ/su 283; placebo 279), (mean age 57.3 [HZ/su 56.8; placebo 57.8] years), 415 were included in the according-to-protocol (ATP) cohort for humoral immunogenicity and 132 in the ATP sub-cohort for CMI. M2 immune responses were higher in the HZ/su group (Table 1). Both co-primary immunogenicity objectives were met (Figure 1). The most frequent local and general solicited AEs were pain and fatigue, reported by 48.2% and 47.8% of all participants (per-group data remain blinded). The frequency of unsolicited AEs, SAEs and pIMDs in the 2 groups was similar (Table 2). CONCLUSION: HZ/su induced robust humoral and cellular immune responses at M2 in HM adults excluding NHBCL and CLL, who completed or are undergoing ICT. No safety concerns were observed up to 6 months post-dose 2. FUNDING: GlaxoSmithKline Biologicals SA DISCLOSURES: L. Oostvogels, GSK group of companies: Employee and Shareholder, Salary and Shares Oxford University Press 2017-10-04 /pmc/articles/PMC5631126/ http://dx.doi.org/10.1093/ofid/ofx163.1040 Text en © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Oostvogels, Lidia
Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial
title Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial
title_full Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial
title_fullStr Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial
title_full_unstemmed Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial
title_short Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in Adults with Hematologic Malignancies: A Phase III, Randomized Clinical Trial
title_sort immunogenicity and safety of an adjuvanted herpes zoster subunit candidate vaccine in adults with hematologic malignancies: a phase iii, randomized clinical trial
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5631126/
http://dx.doi.org/10.1093/ofid/ofx163.1040
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