E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Herpes Zoster (HZ) and its related complications |
|
E.1.1.1 | Medical condition in easily understood language |
Herpes zoster (Shingles) disease |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019974 |
E.1.2 | Term | Herpes zoster |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 |
- To evaluate vaccine response rate (VRR) for anti-gE humoral immune responses at Month 2, following a two-dose administration of the HZ/su vaccine, in all subjects.
- To evaluate the safety and reactogenicity following administration of HZ/su vaccine as compared to placebo from the first vaccination up to 30 days post last vaccination in all subjects. |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the anti-gE humoral immune response at Month 2, following a two-dose administration of the HZ/su vaccine, as compared to placebo, in all subjects.
- To characterise anti-gE humoral immune responses at Months 0, 1, 2, 7 and 13, within the HZ/su and placebo groups, in all subjects.
- To evaluate VRR for gE-specific CD4+ T-cell mediated immune responses at Month 2, following a two-dose administration of the HZ/su vaccine, in the CMI sub-cohort.
- To evaluate gE-specific CD4+ T-cell mediated immune (CMI) response at Month 2 following a two-dose administration of the HZ/su vaccine, as compared to placebo, in the CMI sub-cohort.
- To characterise gE-specific CD4+ T-cell mediated immune responses at Months 0, 2 and 13, within the HZ/su and placebo groups, in the CMI sub-cohort.
- To evaluate safety following administration of HZ/su vaccine, as compared to placebo, from 30 days post last vaccination until study end in all subjects. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- A male or female, aged 18 years or older, and having reached the age of legal consent, on the date the informed consent is signed.
- Written informed consent obtained from the subject.
- Subject who has received an ABO compatible allogeneic renal transplant.
- Subject receiving maintenance immunosuppressive therapy for the prevention of allograft rejection for a minimum of one month (30 days) prior to the first vaccination.
- Subject without an episode of allograft rejection over the previous three months (90 days) prior to the first vaccination.
- Subject with stable renal function. Stability defined as: - less than 20% variability between last two creatinine measurements or calculated glomerular filtration rate [GFR]; - or in the opinion of the investigator after investigator review of more than the last two creatinine measurements or calculated GFRs.
- Subject not less than 4 months (120 days) and not more than 18 months (547 days) after allograft transplantation at the time of the first vaccination.
- Subjects with multiple dialysis options (peritoneal and/or more than one anatomical access site for haemodialysis) in the event acute or chronic dialysis is needed.
- Female subjects of non-childbearing potential may be enrolled in the study.
- Female subjects of childbearing potential may be enrolled in the study, if the subject:
*has practiced adequate contraception for 30 days prior to vaccination, and
*has a negative pregnancy test on the day of the first vaccination, and
*has agreed to continue adequate contraception during the primary treatment period and for 2 months after completion of the vaccination series. |
|
E.4 | Principal exclusion criteria |
- Any primary kidney disease with a high incidence of recurrent primary kidney disease.
- Evidence of recurrent primary kidney disease within the current allograft.
- Previous allograft loss secondary to recurrent primary kidney disease.
* Multiple kidney transplants are allowed if the reason for a previous alograft's loss is not recurrent primary kidney disease.
- More than one organ transplanted (i.e., kidney-liver, double-kidney or kidney-other organ(s) transplanted).
- History of events that, in the opinion of the investigator, may put subject at increased risk for chronic allograft dysfunction (e.g., delayed graft function, peri-operative complications).
- Histologic reports of chronic allograft injury (e.g., transplant glomerulopathy, arteriopathy, C4d deposition).
- Evidence of significant proteinuria in the opinion of the investigator.
- Panel reactive antibody score (PRA or cPRA) that is unknown at the time of transplant.
- Any autoimmune or potential immune-mediated disease, including primary kidney disease.
- Any confirmed or suspected HIV, primary immunodeficiency disease, disseminated or untreated malignancy, or systemic infection.
- Use of anti-CD20 or other B-cell monoclonal antibody agents (e.g., rituximab) as induction, maintenance and/or therapeutic immunosuppressive therapy for the prevention of allograft rejection within 9 months (274 days) of first dose of study vaccine/placebo.
- Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine/placebo, or planned use during the study period.
- Concurrent or planned participation in another clinical study, at any time during the study period, which has exposed or will expose the subject to an investigational or a non-registered product.
- Administration or planned administration of a live vaccine within 30 days prior to the first dose of study vaccine and ending 30 days after the last dose of study vaccine, or, administration or planned administration of a non-replicating vaccine within 8 days prior to or within 14 days after either dose of study vaccine.
- Planned administration during the study of a varicella or HZ vaccine other than the study vaccine.
- Previous vaccination against HZ or varicella within the 12 months preceding the first dose of study vaccine/placebo.
- Occurrence of varicella or HZ per clinical history, within the 12 months preceding the first dose of study vaccine/placebo.
- Failure to fully complete the 7-day pre-vaccination diary card distributed at the Pre-vaccination visit.
- Evidence or high suspicion, in the opinion of the investigator, of noncompliance or nonadherence to use of induction and/or maintenance immunosuppressive therapies.
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or study material and equipment.
- Any condition which, in the judgment of the investigator, would make intramuscular injection unsafe.
- Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study.
- Acute disease and/or fever at the time of vaccination.
*Fever is defined as temperature ≥ 37.5°C /99.5°F by oral route. The preferred route for recording temperature in this study will be oral.
*Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
- Pregnant or lactating female.
- Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 3. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Evaluation of anti-gE humoral immunogenicity, in all subjects, in terms of vaccine response:
*Vaccine response for anti-gE humoral immunogenicity, as determined by ELISA.
- Occurrence of solicited local and general symptoms:
*Occurrence, intensity and duration of each solicited local symptom.
*Occurrence, intensity, duration and relationship to vaccination of each solicited general symptom.
- Occurrence of unsolicited symptoms:
*Occurrence, intensity and relationship to vaccination of unsolicited adverse events (AEs), according to the MedDRA classification.
- Occurrence of serious adverse events (SAEs):
*Occurrence and relationship to vaccination of all SAEs.
- Occurrence of adverse events of specific interest (AESIs):
*Occurrence of any potential Immune-Mediated Diseases (pIMDs).
*Occurrence of biopsy-confirmed renal allograft rejection.
- Evaluation of allograft function:
*Allograft function as measured by serum creatinine. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Anti-gE humoral immunogenicity: Month 2
- Solicited local and general symptoms: within 7 days (Days 0-6) after each vaccination
- Unsolicited symptoms: during 30 days (Days 0-29) after each vaccination
- SAEs: from the first vaccination up to 30 days post last vaccination
- AESIs: from first vaccination up to 30 days post last vaccination
- Allograft function: from first vaccination up to 30 days post last vaccination |
|
E.5.2 | Secondary end point(s) |
- Evaluation of anti-gE humoral immunogenicity in terms of antibody concentrations:
*Anti-gE Ab concentrations, as determined by ELISA in all subjects.
*Vaccine response for anti-gE humoral immunogenicity, as determined by ELISA in all subjects.
- gE-specific CD4+ T-cell mediated immunogenicity, in the CMI sub-cohort:
*Frequencies of gE-specific CD4+ T-cells, expressing at least two activation markers, as determined by in vitro ICS.
*Vaccine response for gE-specific CD4+ T-cells expressing at least two activation markers, as determined by in vitro ICS.
- Occurrence of SAEs:
*Occurrence and relationship to vaccination of all SAEs.
- Occurrence of AESIs:
*Occurrence of any pIMDs.
*Occurrence of biopsy confirmed renal allograft rejection.
- Evaluation of allograft function:
*Allograft function as measured by serum creatinine.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Anti-gE Ab concentrations: at Months 0, 1, 2, 7 and 13
- Vaccine response for anti-gE humoral immunogenicity: at Months 1, 7 and 13
- Frequencies of gE-specific CD4+ T cells: at Months 0, 2 and 13
- Vaccine response for gE-specific CD4+ T cells: at Months 2 and 13
- SAEs: from 30 days post last vaccination until study end (Month 13)
- AESIs: from 30 days post last vaccination until study end (Month 13)
- Allograft function: from 30 days post last vaccination until study end (Month 13)
|
|
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 |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Colombia |
Czech Republic |
Korea, Republic of |
Panama |
Spain |
Taiwan |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 11 |