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Immunological study of herpes zoster vaccine in diabetes and dialysis patients

Immunological study of herpes zoster vaccine in diabetes and dialysis patients

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Sex (male / female) (n (%)): Control group: 29 (45.3) / 35 (54.7) Diabetes group: 38 (59.4) / 26 (40.6) Dialysis group: 39 (59.1) / 27 (40.9) Age at consenting (year) (mean +/- S.D.): Control group: 61.0 +/- 8.0 Diabetes group: 66.9 +/- 8.7 Dialysis group: 66.8 +/- 8.7 Presence of diabetes (n (%)): Control group: 0 (0.0) Diabetes group: 64 (100.0) Dialysis group: 33 (50.0) Presence of dialysis (n (%)): Control group: 0 (0.0) Diabetes group: 0 (0.0) Dialysis group: 66 (100.0) Current complication of herpes zoster (n (%)): Control group: 0 (0.0) Diabetes group: 0 (0.0) Dialysis group: 0 (0.0) History of herpes zoster in more than 5 years ago before consenting (n (%)): Control group: 11 (17.2) Diabetes group: 8 (12.5) Dialysis group: 1 (1.5)

2024/02/13 Protocol firstly approved by certified review board 2024/04/16 First publication in jRCT 2024/05/10 Provisional registration of first participant 2024/05/15 Actual registration of first participant 2024/09/12 Provisional registration of last participant 2024/09/19 Actual registration of last participant 2025/05/26 Development of Statistical Analysis Plan (ver.1.0) under blinded manner 2025/11/18 Last visit of last participant 2026/02/05 Databese lock 2026/03/30 Development of Statistical Analysis Report (ver.1.0)

<Control group> [Death (n (%))] 0 (0.0) [Adverse event (n (%))] 59 (89.4) [Serious adverse event (n (%))] 2 (3.0) [Disease-or-the-like (n (%))] 56 (84.8) [Serious disease-or-the-like (n (%))] 0 (0.0) <Diabetes group> [Death (n (%))] 0 (0.0) [Adverse event (n (%))] 63 (98.4) [Serious adverse event (n (%))] 9 (14.1) [Disease-or-the-like (n (%))] 60 (93.8) [Serious disease-or-the-like (n (%))] 0 (0.0) <Dialysis group> [Death (n (%))] 1 (1.5) [Adverse event (n (%))] 51 (77.3) [Serious adverse event (n (%))] 17 (25.8) [Disease-or-the-like (n (%))] 20 (30.3) [Serious disease-or-the-like (n (%))] 0 (0.0)

- The proportion of cases meeting the criteria for the primary endpoint -vaccine response rate (VRR)- was high one month after the second dose of the herpes zoster vaccine (month 3), at 100% in both the control group and the diabetes group, and 93.9% in the dialysis group. - However, while the control group and the diabetes group maintained the VRR of 90% or higher even one year after the second dose of the herpes zoster vaccine (month 14), it in the dialysis group was lower as 70.5%. - Anti-VZV gE antibody titers also greatly increased in all groups: approximately 10-fold one month after the first herpes zoster vaccination (month 2) and approximately 2-fold again one month after the second herpes zoster vaccination (month 3). - Subsequently, anti-VZV gE antibody titers gradually declined in all groups; however, while the control group and the diabetes group maintained levels of 20,000 mIU/mL or higher even one year after the second herpes zoster vaccine dose (month 14), it in the dialysis group was lower as approximately 15,000 mIU/mL. - These findings suggested that while the herpes zoster vaccine was immunogenic even in dialysis patients who generally have impaired immune function, its efficacy may wane more rapidly compared to patients with diabetes or the control group. - In the control and diabetic groups, adverse drug reactions (disease-or-the-like) occurred at a high frequency of over 80%, whereas in the dialysis group, the frequency was low at 30.3%. - In all groups, the most common adverse drug reaction was pain at the vaccination site; however, while it occurred at a high frequency of 77.3% and 90.6% in the control group and the diabetes group, respectively, the frequency was low at 30.3% in the dialysis group. - One death (1.5%) occurred in the dialysis group; however, because this was a sudden death due to cardiac arrest by hyperkalemia that occurred two days after the last dialysis session, it was reported to be unrelated to the study. - Any serious adverse events occurred in 2 cases (3.0%) in the control group, 9 cases (14.1%) in the diabetes group, and 17 cases (25.8%) in the dialysis group. - No serious adverse drug reactions were observed in any of the groups.

The vaccine response rate for the herpes zoster vaccine was as high as more than 90% in all groups one month after the second dose; however, anti-VZV gE antibodies declined more rapidly in dialysis patients. The frequency of adverse drug reactions was high as more than 80% in the diabetes and control groups, but low as 30% in the dialysis group. Further studies will be required to confirm the efficacy of the herpes zoster vaccine in patients with diabetes or dialysis to establish vaccination strategy.

Sept. 03, 2026

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs031240031

Namkoong Ho

Keio University Hospital

35 Shinanomachi, Shinjuku-ku, Tokyo

hounamugun@keio.jp

Yoshifuji Ayumi

Keio University Hospital

35 Shinanomachi, Shinjuku-ku, Tokyo

+81-3-5363-3761

ayutsuranaide@keio.jp

Complete

April. 16, 2024

Interventional

non-randomized controlled trial

open(masking not used)

active control

parallel assignment

prevention purpose

Subjects who meet all of the following criteria are included in this study:
1. Male and female aged between 50 years and 80 years at giving their consent
2. Subjects who meet one of the following criteria
i) Group A: Control group
Subjects who have not been diagnosed* with diabetes mellitus or chronic kidney disease (Stage G3b or higher) at the time of consent, nor had they been diagnosed in the past
ii) Group B: Diabetes mellitus group
Patients who are diagnosed with type 2 diabetes mellitus
Patients treated with any therapeutic agents for diabetes mellitus
Patients who have not been diagnosed* with chronic kidney disease (Stage G3b or higher) at the time of consent, nor had they been diagnosed in the past
iii) Group C: Hemodialysis group
Patients with hemodialysis
3. Subjects who give their consent in a written form
*The diagnostic criteria for diabetes mellitus are based on the "Diabetes Treatment Guide 2022-2023" and the diagnosis of chronic kidney disease is based on the "CKD Severity Classification (CKD Practice Guide 2012)".

Subjects who fall into any of the following criteria are excluded from participating in the study
<Exclusion criteria at the provisional registration>
1. Subjects with a history of herpes zoster within five years before giving their consent
2. Subjects with a history of vaccination with the herpes zoster vaccine
3. Subjects with a history of any vaccination within one month before giving their consent
4. Subjects who have a plan to receive other vaccinations within one month after the first and second vaccination of RZV in this study
5. Subjects with hematological coagulation disorder at giving their consent
6. Subjects with malignancy and those who received treatments with systemic steroids, or systemic administration of immunosuppressive agents or immunomodulatory agents within two years before giving their consent
7. Subjects who Patients who received a hematopoietic stem cell transplant or any kind of organ donation in the past
8. Subjects who are clearly suffering from a serious acute illness at giving their consent
9. Subjects who have clearly experienced anaphylaxis due to any of the ingredients of this agent
10. Pregnant woman, or premenopausal women who do not agree to contraception
11. Subjects who are participating in other interventional trials
12. Subjects who need legal representative for giving consent
13. Subjects who are considered to be unsuitable for participating in this study by investigators

<Exclusion criteria at the registration>
14. Subjects with anti-HIV antibody positive at giving their consent or the screening tests*
15. Subjects with thrombocytopenia (Plt < 50,000/microL) or hepatic disorder (ALT or AST is 3 times or more higher than the upper limit of the standard value in each research institution) at giving their consent or the screening tests*
16. Subjects with urine protein creatinine ratio of 0.5 g/g Cre in the Group A (Control group) and the B (Diabetes mellitus group) at giving their consent or the screening tests*
17. Subjects with HbA1c of 6.5% or higher in the Group A (Control group) at giving their consent or the screening tests*
18. Subjects with eGFR of less than 45 mL/min/1.73m2 in the Group A (Control group) and the B (Diabetes mellitus group) at giving their consent or the screening tests *
19. Subjects who have developed herpes zoster between the time of provisional registration and the time of registration
20. Subjects who received herpes zoster vaccine between the time of provisional registration and the time of registration
21. Subjects who received any vaccine between the time of provisional registration and the time of registration
22. Subjects who had any hematological coagulation disorder between the time of provisional registration and the time of registration
23. Subjects who have been diagnosed with malignant tumor or treated with systemic steroids, immunosuppressive drugs or immunomodulators from the time of provisional registration and the time of registration
24. Subjects who received a hematopoietic stem cell transplant or any kind of organ donation between the time of provisional registration and the time of registration
25. Subjects who are found to be pregnant or premenopausal women who refused to consent to contraception between the time of provisional registration and the time of registration
26. Subjects who have participated in other intervention studies between the time of provisional registration and the time of registration
27. Other, subjects whose attending physician determines that they are not eligible to participate in this study
* If the measurement was performed under regular medical care within one month prior to the time of consent, the most recent test result at the time of consent is used to determine the eligibility criteria. If the measurement has not been performed under regular medical care within one month prior to obtaining consent, a screening test will be performed after provisional enrollment, and the results of that screening test will be used to determine eligibility criteria. If data are available for both tests, the subject will be excluded if any of the exclusion criteria are met by either test.

Both

Herpes Zoster

Vaccination of dry recombinant Herpes Zoster vaccine (Shingrix)

Herpes Zoster, Diabetes mellitus, End-Stage Renal Disease

dry recombinant Herpes Zoster vaccine

Each Vaccine Response Rate (VRR)* at observation points 2 (2 months), 3 (3 months), 4 (8 months) and 5 (14 months)
*VRR: Proportion of cases meeting the following criteria
- Serum anti-varicella-zoster virus (VZV) glycoprotein E (gE) antibody level (anti-VZV gE antibody level) at Observation Point 1 (baseline) less than 97 milli-International Units (mIU)/ml: Anti-VZV gE antibody level at this Observation Point was 388mIU/ml or higher
- Anti-VZV gE antibody level at Observation Point 1 (baseline) is greater than or equal to 97mIU/ml: Anti-VZV gE antibody level at this Observation Point is greater than or equal to 4 times the level at Observation Point 1 (baseline)

1. Summary statistics of anti-VZV gE antibody levels at each observation point.
2. Seroconversion rates at each observation point (percentage of cases with anti-VZV gE antibody levels of 97mIU/ml or higher).
3. Summary statistics of VZV-specific cellular and humoral immunity at each observation point (VZV-specific T cell and B cell profiles measured by flow cytometry)

+81-3-5363-3503

Feb. 13, 2024

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