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自家造血幹細胞移植（auHSCT）

自家移植後５

組換え帯状疱疹ワクチン(RZV)を18歳以上のauHSCT患者に移植50～70日後に1～2ヵ月間隔で2回筋肉内接種し、有効性、安全性、免疫原性を評価する第3相無作為化観察者盲検プラセボ対照多施設共同臨床試験。5,22–24　

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study-design-to-evaluate-the-prophylactic-efficacy,-safety-and-immunogenicity-of-the-recombinant-zoster-vaccine,-when-administered-intramuscularly-on-a-two-dose-schedule-to-autologous-haematopoietic-stem-cell-transplant-recipients.-participants-were-randomised-1-to-1-to-receive-two-doses-of-either-the-recombinant-zoster-vaccine-or-placebo-1-to-2-months-apart.-visits-were-carried-out-at-months-0,-1,-2,-13-and-25.-participants-were-contacted-by-telephone-monthly-

†Visit 3: approximately 1 month after the second vaccination.
*Second dose was administered 1 to 2 months after the first dose.
Blood sampling collected from all subjects at Visit 1 and Visit 3. Additional blood samples collected from sub-cohorts at all study visits.

auHSCT, autologous haematopoietic stem cell transplant; RZV, recombinant zoster vaccine; TVC, total vaccinated cohort; YOA, years of age.

帯状疱疹（HZ）に対する年齢層別のワクチン有効性およびその他のHZ関連エンドポイント:5,22

 

RZV

N (n)

Placebo

N (n)

 

VE

 

  
% LL UL
VE by Age          
18–49 213 (9) 212 (29) 71.8 38.8 88.3
≥50 657 (40) 639 (106) 67.3 52.6 77.9
Other HZ-related endpoints  
PHN

 870 (1) 851 (9) 89.3 22.5 99.8
HZ-related hospitalisations 870 (2) 851 (13) 84.7 32.1 96.6
Other HZ complications* 870 (3) 851 (13) 77.8 19.0 95.9

*Excluding PHN: disseminated zoster: 3 (recombinant zoster vaccine group) and 13 (placebo group); meningoencephalitis: 1 (placebo group); whole study period, median follow-up time approximately 21 months.

HZ, herpes zoster; LL, lower limit; N, number of subjects included in each group; n, number of subjects having at least one confirmed HZ episode; PHN, post-herpetic neuralgia; RZV, recombinant zoster vaccine; UL, upper limit; VE, vaccine efficacy.

2回接種を完了した被験者において、帯状疱疹の予防に対するワクチンの有効性は68.2％であると示されました。5,22

液性免疫応答5,23

column-graph-showing-anti–glycoprotein-e-geometric-mean-concentrations-in-autologous-haematopoietic-stem-cell transplantation-patients-prior-to-and-after-vaccination-with-either-the-recombinant-zoster-vaccine-or-placebo.-highest-anti–glycoprotein-e-geometric-mean-concentrations-were-recorded-one-month-after-dose-two,-which-remained-above-baseline-24-months-after-completion-of-the-vaccination-schedule-

gE, glycoprotein E; GMC, geometric mean concentration; Mo, month; RZV, recombinant zoster vaccine.
Graph based on raw data from the Clinical Trial NCT01610414.23

細胞性免疫応答5

column-graph-showing-frequency-of-glycoprotein-e-specific-c-d-4-plus-t-cells-in-autologous-haematopoietic-stem-cell-transplantation-patients-before-and-after-vaccination-with-the-recombinant-zoster-vaccine-or-placebo.-the-frequency-of-glycoprotein-e-specific-c-d-4-plus-t-cells-was-highest-1-month-after-dose-two-and-subsequently-declined-but-remained-higher-than-before-vaccination-24-months-after-dose-two-

gE, glycoprotein E; IQR, interquartile range; Mo, month; RZV, recombinant zoster vaccine.
Figure based on raw data from Bastidas A, et al. JAMA. 2019;322(2):123–133.5,23

RZVワクチン接種後の液性免疫および細胞性免疫応答は、2回目のワクチン接種後24カ月時点でも接種前より高い値を維持しており、年齢による影響は見られませんでした。5,18,23

column-graphs-depicting-local-and-general-reactions-in-autologous-haematopoietic-stem-cell transplantation-patients-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-local-and-general-reactions-were-more-frequently-reported-by-those-in-the-vaccine-group-compared-with-the-placebo-group.-in-patients-who-received-the-recombinant-zoster-vaccine,-the-most-frequently-reported-local-adverse-reaction-was-pain-at-the-injection-site;-fatigue,-myalgia-and-headache-were-the-most-frequently-reported-general-reactions-

Any symptom, occurrence of the symptom regardless of intensity grade; Grade 3 pain, pain that prevented normal activity; Grade 3 redness/swelling, redness/swelling spreading beyond 100 mm of injection site; Grade 3 symptom, symptom that prevented normal activity; fever defined as a temperature (preferably oral) ≥37.5°C; Grade 3 fever >39.0°C.

GI, gastrointestinal (nausea, vomiting, diarrhoea and abdominal pain); RZV, recombinant zoster vaccine.

Figure based on raw data from Bastidas A, et al. JAMA. 2019;322(2):123-133.

最も頻度が高かった局所および全身性の有害事象 (AE) は、接種部位の疼痛、疲労、筋肉痛でした。5
ワクチン接種後7日以内に発症した局所および全身性の有害事象は、ワクチンを接種した群でプラセボ群よりも頻度が高い事が示されました。5

column-graph-depicting-serious-adverse-events,-related-serious-adverse-events,-potential-immune-mediated-diseases,-fatal-serious-adverse-events,-relapses-of-underlying-diseases-and-unsolicited-adverse-events-in-autologous-haematopoietic-stem-cell-transplantation-patients-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-overall-incidences-were-similar-between-both-groups-

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Grade 3, severe AE that prevents normal activity.

AE, adverse event; auHSCT, autologous haematopoietic stem cell transplant; pIMD, potential immune-mediated disease; RZV, recombinant zoster vaccine; SAE, serious adverse event.

Figure based on raw data from Bastidas A, et al. JAMA. 2019;322(2):123–133.

AE、重篤な有害事象（SAE）、致死的なSAE、免疫の関与が疑われる疾患（pIMD）および基礎疾患の再燃が発生した患者の割合は、RZV群とプラセボ群で同等でした。5

自家造血幹細胞移植（auHSCT）患者におけるワクチンの試験概要・結果

血液悪性腫瘍患者におけるワクチンの試験概要・結果

固形腫瘍患者におけるワクチンの試験概要・結果

腎移植患者におけるワクチンの試験概要・結果

HIV感染症患者におけるワクチンの試験概要・結果

Abbreviations

AE, adverse event; ART, anti-retroviral therapy; ATP, according to protocol; BCL, B-cell lymphoma; CLL, chronic lymphocytic leukaemia; CMI, cell-mediated immunity; gE, glycoprotein E; GI, gastrointestinal; GMC, geometric mean concentration; HIV, human immunodeficiency virus; IQR, interquartile range; LL, lower limit; Mo, month; mTVC, modified total vaccinated cohort; pIMD, potential immune-mediated disease; PHN, post-herpetic neuralgia; Pre, pre-vaccination; Q, quartile; RZV, recombinant zoster virus; SAE, serious adverse event; TVC, total vaccinated cohort; UL, upper limit; VE, vaccine efficacy; VRR, vaccine response rate; YOA, years of age

References

  1. Chen SY, et al. Infection. 2014;42(2):325–334
  2. Zhang D, et al. Adv Ther. 2017;34(7):1610–1621.
  3. Sahoo F, et al. Biol Blood Marrow Transplant. 2017;23(3):505–511.
  4. Winston DJ, et al. Lancet. 2018;391(10135):2116–2127
  5. Bastidas A, et al. JAMA. 2019;322(2):123–133
  6. Habel LA, et al. Cancer Epidemiol Biomarkers Prev. 2013;22(1):82–90
  7. Dagnew AF, et al. Lancet Infect Dis. 2019;19(9):988–1000
  8. Koo S, et al. Transpl Infect Dis. 2014;16(1):17–25
  9. Pergam SA, et al. Transpl Infect Dis. 2011;13(1):15–23
  10. Arness T, et al. Transpl Infect Dis. 2008;10(4):260–268
  11. Mao J, et al. Medicine (Baltimore). 2017;96(48):e8746
  12. Tseng HF, et al. Clin Infect Dis. 2014;59(7):913–919
  13. Blank LJ, et al. J Acquir Immune Defic Syndr. 2012;61(2):203–207
  14. Chakravarty EF. Rheum Dis Clin North Am. 2017;43(1):111–121
  15. Veetil BM, et al. Arthritis Care Res (Hoboken). 2013;65(6):854–861
  16. Khan N, et al. Clin Gastroenterol Hepatol. 2018;16(12):1919–1927
  17. Johnson BH, et al. BMC Infect Dis. 2015;15:502
  18. Dagnew AF, et al. Hum Vaccin Immunother. 2021;17(11):4132–4143
  19. Berkowitz EM, et al. J Infect Dis. 2015;211(8):1279–1287
  20. Vink P, et al. Clin Infect Dis. 2020;70(2):181–190
  21. Vink P, et al. Cancer. 2019;125(8):1301–1312
  22. de la Serna J, et al. Efficacy and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine in Autologous Hematopoietic Stem Cell Transplant Recipients 18 Years of Age or Older: First Results of the Phase 3 Randomized, Placebo-Controlled ZOE-HSCT Clinical Trial. Presented at BMT Tandem Meeting; 25th February 2018; Salt Lake City, UT, USA.
  23. ClinicalTrials.gov. NCT01610414. Available at: https://clinicaltrials.gov/ct2/show/study/NCT01610414 (accessed May 2023).
  24. Zoster-002 Clinical Study Report 115523. Available at: https://www.gsk-studyregister.com/study/4539 (accessed May 2023).
  25. Zoster-039 Clinical Study Report 116428. Available at: https://www.gsk-studyregister.com/en/trial-details/?id=116428 (accessed May 2023)
  26. ClinicalTrials.gov. NCT01798056. Available at: https://clinicaltrials.gov/ct2/show/NCT01798056 (accessed May 2023).
  27. Zoster-028 Clinical Study Report 116427. Available at: https://gsk-clinicalstudyregister.com/files2/116427-Clinical-Study-Result-Summary.pdf (accessed May 2023).
  28. Vink P. Immunogenicity and Safety of a Candidate Subunit Adjuvanted Herpes Zoster Vaccine in Adults with Solid Tumors Vaccinated Before or During Immunosuppressive Chemotherapy Treatment: A Phase II/III, Randomized Clinical Trial. Poster #1349. Presented at IDWeek; 4–8 October, 2017; San Diego, CA, USA.
  29. ClinicalTrials.gov. NCT02058589. Available at: https://clinicaltrials.gov/ct2/show/NCT02058589 (accessed May 2023).
  30. Vink P, et al. Open Forum Infect Dis. 2018;5(suppl 1):S744–S745
  31. Zoster-041 Clinical Study Report 116886. Available at: https://www.gsk-studyregister.com/en/trial-details/?id=116886 (accessed May 2023).
  32. Zoster-015 Clinical Study Report 112673. Available at: https://gsk-clinicalstudyregister.com/files2/gsk-112673-clinical-study-report-redact.pdf (accessed May 2023).

NX-JP-SGX-WCNT-230009 | October 2023