E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Long-term follow-up (LTFU) phase - Immunogenicity assessment
•To evaluate persistence of humoral immunity after primary vaccination course.
Revaccination active phase - Immunogenicity assessment
•To evaluate humoral immunity of Herpes zoster subunit (HZ/su) vaccine post-revaccination Doses 1 & 2. |
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E.2.2 | Secondary objectives of the trial |
LTFU phase - Immunogenicity assessment
•To evaluate persistence of cellular immunity after primary vaccination course.
LTFU phase - safety assessment
•To evaluate safety of HZ/su vaccine from the study ZOSTER-041 last visit to study ZOSTER-073 Visit 3.
Revaccination active phase - Immunogenicity assessment
•To evaluate cell-mediated immunity post-revaccination Doses 1 & 2.
Revaccination follow-up phase – Immunogenicity assessment
•To evaluate persistence of humoral and cell-mediated immune responses post-revaccination Dose 2.
Revaccination active and follow-up phases - Safety assessment
•To evaluate reactogenicity and safety of the HZ/su vaccine after each revaccination. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for enrolment
•Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol or/and subjects’ Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
•Written informed consent obtained from the subject/LAR(s) of the subject prior to performance of any study-specific procedure.
•Subjects who previously participated in study ZOSTER-041 and completed the full 2 dose HZ/su primary vaccination course
Inclusion criteria for revaccination
•Subjects receiving maintenance CIS therapy for the prevention of allograft rejection for a minimum of one month prior to the first revaccination.
•Subjects without an episode of allograft rejection within 90 days prior to the first revaccination visit.
•Female subjects of non-childbearing potential may be revaccinated. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
•Female subjects of childbearing potential may be revaccinated, if the subject:
–has practiced adequate contraception for 30 days prior to revaccination, and
–has a negative pregnancy test on the day of revaccination, and
–has agreed to continue adequate contraception up to 2 months after completion of the revaccination series. |
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E.4 | Principal exclusion criteria |
Exclusion criteria for enrolment
Medical conditions
•Vaccination against HZ since completion of study ZOSTER-041
•Significant underlying illness that, in the opinion of the investigator, is expected to prevent completion of the study
•Any other condition that, in the opinion of the investigator, would interfere with the evaluations required by the study
Prior/Concurrent clinical study experience
•Concurrently participating in another interventional vaccine or immunosuppressive clinical study, in which the subject is exposed to an investigational or a non-investigational vaccine/product (drug) at any time during the ZOSTER-073 study
Exclusion criteria for revaccination
Medical conditions
•History of confirmed HZ within one year before revaccination visit (Visit 3)
•More than one organ transplanted
•Any additional confirmed or suspected immunosuppressive or immunodeficient condition
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine
•Any other condition that, in the opinion of the investigator, would interfere with the evaluations required by the study or make vaccination unsafe
Prior/Concomitant therapy
•Administration or planned administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first revaccination dose of study vaccine and ending at Visit 5 (Month 26)
•Use of anti-CD20 or other B-cell monoclonal antibody agents as maintenance and/or therapeutic immunosuppressive therapy for the prevention of allograft rejection within 9 months of first revaccination dose of study vaccine
•Evidence or high suspicion, in the opinion of the investigator, of noncompliance or nonadherence to use of maintenance immunosuppressive therapies
•Planned administration/administration of a live vaccine in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration
•Planned administration/administration of a non-replicating or subunit vaccine, not foreseen by the study protocol, in the period starting 8 days before and ending 30 days after each dose of study vaccine
Other exclusion criteria for revaccination
•Pregnant or lactating female
•Female planning to become pregnant or planning to discontinue contraceptive precautions up to 2 months post-revaccination Dose 2
•Any condition which, in the judgment of the investigator, would make intramuscular injection unsafe |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Evaluation of persistence of humoral immunity in terms of anti-glycoprotein E (anti-gE) antibody concentrations as determined by Enzyme-Linked Immunosorbent Assay (ELISA) at Day 1 in the LTFU phase
2. Anti-gE antibody concentrations as determined by ELISA at Month 12, in the LTFU phase
3. Anti-gE antibody concentrations as determined by ELISA at Month 24, in the LTFU phase
4. Anti-gE antibody concentrations as determined by ELISA at pre-revaccination, in the revaccination active phase
5. Anti-gE antibody concentrations as determined by ELISA at 1-month post-revaccination dose 1, in the revaccination active phase
6. Anti-gE antibody concentrations as determined by ELISA at 1-month post-revaccination Dose 2 in the revaccination active phase |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At Day 1
2. At Month 12
3. At Month 24
4. At Month 24 (pre-vaccination)
5. At Month 25
6. At Month 26 |
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E.5.2 | Secondary end point(s) |
1. Evaluation of cell-mediated immune (CMI) responses in terms of frequencies of gE-specific CD4+ T-cells as determined by Intracellular Cytokine Staining (ICS) at day 1, in the LTFU phase
2. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 12, in the LTFU phase
3. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 24 in the LTFU phase
4. Percentage of subjects with any Serious Adverse Events (SAEs) related to primary vaccination in the LTFU phase
5. Number of subjects with history of suspected or confirmed Herpes Zoster (HZ) episode in the LTFU phase
6. Number of subjects with a confirmed HZ episode in the LTFU phase
7. Number of subjects with a history of suspected or biopsy-proven allograft rejections in the LTFU phase
8. Number of subjects with biopsy-proven allograft rejections in the LTFU phase
9. Number of subjects with allograft dysfunction related to allograft rejection episodes in the LTFU phase
10. Number of subjects with allograft dysfunction related to HZ episodes in the LTFU phase
11. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at pre-vaccination in the Revaccination active phase
12. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 25 in the Revaccination active phase
13. Frequencies of gE-specific CD4+ T-cells as determined by ICS, at month 26 in the Revaccination active phase
14. Anti-gE antibody concentrations as determined by ELISA at 12 months post-revaccination Dose 2, in the Revaccination follow-up phase
15. Anti-gE antibody concentrations as determined by ELISA at 24 months post-revaccination Dose 2, in the Revaccination follow-up phase
16. Frequencies of gE-specific CD4+ T-cells as determined by ICS at month 37 in the Revaccination follow-up phase
17. Frequencies of gE-specific CD4+ T-cells as determined by ICS at month 49 in the Revaccination follow-up phase
18. Percentage of subjects with at least one solicited local Adverse event (AE) after each revaccination in the revaccination active and follow-up phases
19. Percentage of subjects with any solicited general AE after each revaccination in the revaccination active and follow-up phases
20. Percentage of subjects with any unsolicited AEs after each revaccination in the revaccination active and follow-up phases
21. Percentage of subjects with any SAE, in the Revaccination active phase
22. Percentage of subjects with any SAE, in the Revaccination follow-up phase
23. Percentage of subjects with any related SAE, in the Revaccination active phase
24. Percentage of subjects with any related SAE, in the Revaccination follow-up phase
25. Number of subjects with biopsy-proven allograft rejections in the Revaccination active phase
26. Number of subjects with biopsy-proven allograft rejections in the Revaccination follow-up phase
27. Percentage of subjects with any Potential immune-mediated diseases (pIMD) in the Revaccination active phase
28. Percentage of subjects with any Potential immune-mediated diseases (pIMD) in the Revaccination follow-up phase
29. Number of subjects with a confirmed HZ episode in the Revaccination active phase
30. Number of subjects with a confirmed HZ episode in the Revaccination follow-up phase
31. Number of subjects with allograft dysfunction following revaccination in the revaccination active phase
32. Number of subjects with allograft dysfunction following revaccination in the revaccination follow-up phase
33. Number of subjects with allograft dysfunction related to allograft rejection in the Revaccination active phase
34. Number of subjects with allograft dysfunction related to allograft rejection in the Revaccination follow-up phase
35. Number of subjects with allograft dysfunction related to HZ episodes in the Revaccination active phase
36. Number of subjects with allograft dysfunction related to HZ episodes in the Revaccination follow-up phase |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At Day 1
2. At Month 12
3. At Month 24
4. From Month 13 (last visit in study ZOSTER-041) to Month 24 (Visit 3 in study ZOSTER-073)
5 and 7. From Month 13 (last visit in study ZOSTER-041) to Day 1 (Visit 1 in study ZOSTER-073)
6 and 8. From Day 1 to Month 24
9 and 10. From Month 13 (last visit in study ZOSTER-041) to Month 24 (Visit 3 in study ZOSTER-073)
11. At Month 24 (pre-vaccination)
12. At Month 25
13. At Month 26
14, 16, 22 and 28. At Month 37
15 and 17. At Month 49
18 and 19. Within 7 days after each revaccination
20. Within 30 days after each revaccination
21, 23, 25, 27, 29, 31, 33 and 35. From Month 24 to Month 26
24 and 26. At Month 37 and Month 49
30, 34 and 36. From Month 26 to Month 49
32. From Month 26 to Month 37 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Finland |
Korea, Republic of |
Panama |
Spain |
Taiwan |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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No later than 8 months after LSLV |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 22 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 22 |