E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Herpes Zoster
Renal transplant
Pediatric population
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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 |
•To evaluate reactogenicity (up to Day 7) and safety (up to Month 2) following administration of PED-HZ/su in each age category (1-11 and 12-17 years)
•To evaluate humoral immune responses following administration of PED-HZ/su in each age category (1-11 and 12-17 years) at Month 2
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E.2.2 | Secondary objectives of the trial |
•To evaluate safety following administration of PED-HZ/su in each age category (1-11 and 12-17 years) from Day 1 up to Month 13
•To describe the occurrence of cases of HZ in each age category (1-11 and 12-17 years)
•To evaluate reactogenicity and safety for the entire study population (1-17 years) following administration of PED-HZ/su
•To characterise humoral immune responses following administration of PED-HZ/su
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subjects’ parent(s)/Legally Acceptable Representative(s) [LAR(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol
•Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
•Written informed assent obtained from the subjects when applicable according to local requirements.
•A male or female between, and including, 1 and 17 years of age at the time of randomisation (Visit Day 1)
•Body weight ≥ 6 kg/13.23 pounds.
•A subject is eligible if they meet at least one of the following criteria:
-Documented previous VZV vaccination OR
-Medically verified varicella OR
-Seropositive for VZV prior to transplantation.
•Subjects with renal transplant more than six months (180 days) prior randomization (Visit Day 1)
•Subject who has received an ABO compatible allogeneic renal transplant (allograft).
•Subject with stable renal function with stability defined as <20% variability between the last two creatinine measurements or calculated glomerular filtration rate (GFR) or based on investigator opinion after review of multiple creatinine measurements or calculated GFRs.
•Subject receiving maintenance immunosuppressive therapy for the prevention of allograft rejection for a minimum of one month (30 days) prior to randomization (Visit Day 1).
•Female subjects of childbearing potential may be enrolled in the study, if the subject
-has practiced adequate contraception for 30 days prior to Visit Day 1 and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series
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E.4 | Principal exclusion criteria |
Medical conditions
•Any primary kidney disease with a high incidence of recurrent primary kidney disease within the allograft
•Evidence of recurrent primary kidney disease within the current allograft
•Previous allograft loss secondary to recurrent primary kidney disease
•History of more than one organ transplanted
•Subjects with an episode of acute allograft rejection over the six months (180 days) prior to enrolment or receipt of treatment for rejection during the six months (180 days) prior to enrolment
•Panel Reactive Antibodies (PRA) calculated PRA (cPRA) or Calculated Reaction Frequency (cRF) score that is unknown at the time of transplant
•VZV serostatus unknown prior to transplant
•Subjects with advanced chronic kidney disease
•Evidence of significant proteinuria
•Subjects without multiple dialysis options in the event acute or chronic dialysis needed.
•History of unstable or progressive neurological disorder.
•Subjects <= 5 years of age with a history of one or more simple or complex febrile seizures
•Subjects > 5 years with history of one or more complex febrile seizures
•Occurrence of a varicella or HZ episode by clinical history within the 6 months (180 days) preceding Visit Day 1
•Any autoimmune disease, with the following exceptions which do not constitute an exclusion criterion:
-IgA nephropathy
-Rapidly progressive glomerulonephritis
-Membranous glomerulonephritis
-Idiopathic Type I membranoproliferative glomerulonephritis
-Diabetes mellitus (type 1 and 2) with diabetic nephropathy
•Confirmed or suspected Human Immunodeficiency Virus or primary immunodeficiency disease
•Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine
•Any condition which, in the judgement of the investigator would make intramuscular injection unsafe
Prior/Concomitant therapy
•Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before Visit Day 1 (Day -29 to Day -1), or planned use during the study period. Subjects on treatment for rejection with ongoing treatment with T-cell depleting Ab or IL2R Ab
•Use of anti-CD20 or other B-cell monoclonal antibody agents within 1 year of Visit Day 1 or planned administration during the duration of the study
•Administration of blood products prior to 3 months (90 days) of enrolment or planned administration during the duration of the study
•Administration of immunoglobulins prior to 6 months (180 days) of enrolment or planned administration of immunoglobulins during the duration of the study
•Administration or planned administration of a vaccine in the period starting 30 days before Visit Day 1 up to Visit Month 2
•Previous vaccination against HZ
•Varicella vaccination within the 6 months (180 days) preceding Visit Day 1
•Planned administration during the study of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine
Prior/Concurrent clinical study experience
•Concurrent or planned participation in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product
-available locally through compassionate use programs,
-submitted for and pending local/country registration,
-approved and registered for use in other countries with well-documented Summary of Product Characteristics or Prescribing Information
-The name of the active component(s) of these immunosuppressants must be provided in the concomitant medication listing
Other exclusions
•Child in care
•Pregnant or lactating female
•Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) between one month (30 days) prior to Visit Day 1 through two months (60 days) after Visit Month 1.
•Evidence or high suspicion, in the opinion of the investigator, of non-compliance or non-adherence to use of induction and/or maintenance immunosuppressive therapies.
•Failure to fully complete the 7-day pre-vaccination diary card distributed at the Pre-vaccination visit
-Completion must cover the 7 days immediately prior to randomisation (Visit Day 1)
-Completion is defined as a minimum of 6 days completed
-Subjects with less than 6 days completed may be offered a new date for Visit Day 1 and the opportunity to comply with the completion of the 7-day pre-vaccination diary card prior to the new planned Visit Day 1
•Any study personnel or their immediate dependants, family, or household member |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Number of subjects from the interventional groups, with solicited local adverse events (AEs)
2. Number of subjects from the interventional groups, with solicited general AEs
3. Number of subjects from the control groups with solicited general symptoms
4. Number of subjects from the control groups with solicited general symptoms
5. Number of subjects from the interventional groups with unsolicited AEs after each vaccination
6. Number of subjects from the control groups with unsolicited symptoms
7. Number of subjects from the control groups with unsolicited symptoms
8. Number of subjects with serious adverse events (SAEs), potential immune mediated diseases (pIMDs) and biopsy confirmed renal allograft rejection
9. Number of subjects from the interventional groups with seizures
10. Number of subjects from the non-interventional groups with seizures
11. Number of subjects from the non-interventional groups with seizures
12. Number of subjects from the interventional groups with generalized convulsive seizures
13. Number of subjects from the non-interventional groups with generalized convulsive seizures
14. Number of subjects from the non-interventional groups with generalized convulsive seizures
15. Percentage of subjects with Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Within 7 days after each vaccination
2. Within 7 days after each vaccination
3. Within 7 days after Visit Day 1
4. Within 7 days after Visit Month 1
5. Within 30 days after each vaccination
6. Within 30 days after Visit Day 1
7. Within 30 days after Visit Month 1
8. From Visit Day 1 up to Visit Month 2
9. Within 30 days after each vaccination
10. Within 30 days after Visit Day 1
11. Within 30 days after Visit Month 1
12. Within 7 days after each vaccination
13. Within 7 days after Visit Day 1
14. Within 7 days after Visit Month 1
15. At Month 2 (one-month post-dose 2) |
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E.5.2 | Secondary end point(s) |
1. Number of subjects with SAEs, pIMDs and biopsy confirmed renal allograft rejections from day 1 to month 13
2. Occurrence of Herpes Zoster cases
3. Number of subjects from the interventional pooled age group with solicited local AEs
4. Number of subjects from the interventional pooled age group with solicited general AEs
5. Number of subjects from the non-interventional pooled age group with solicited general symptoms
6. Number of subjects from the interventional pooled age group with unsolicited AEs after each vaccination
7. Number of subjects from the non-interventional pooled age group with unsolicited symptoms
8. Number of subjects from the pooled age groups with any SAEs, pIMDs and biopsy confirmed renal allograft rejections
9. Number of subjects from the pooled age groups with HZ
10. Number of subjects from the interventional pooled age group with seizures
11. Number of subjects from the non-interventional pooled age group with seizures
12. Number of subjects from the interventional pooled age group with generalized convulsive seizures
13. Number of subjects from the non-interventional pooled age group with generalized convulsive seizures
14. Vaccine Response Rate (VRR) for Anti-glycoprotein (Anti-gE) antibody concentrations
15. Median fold increase of anti-gE antibody concentrations
16. Percentage of subjects with anti-gE antibody concentrations in terms of GMCs
17. Percentage of subjects in the interventional pooled age group, with Anti-gE antibody concentrations in terms of GMCs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From Visit Day 1 up to Visit Month 13
2. From Visit Day 1 until Visit Month 13
3. Within 7 days after each vaccination
4. Within 7 days after each vaccination
5. Within 7 days after Visit Day 1 and visit Month 1
6. Within 30 days after each vaccination
7. Within 30 days after Visit Day 1 and Visit Month 1
8. From Visit Day 1 until Visit Month 2 and From Visit Day 1 until Visit Month 13
9. From Visit Day 1 until Visit Month 13
10. Within 30 days after each vaccination
11. Within 30 days after Visit Day 1 and Visit Month 1
12. Within 7 days after each vaccination
13. Within 7 days after Visit Day 1 and Visit Month 1
14. At Month 2 and Month 13
15. At Month 2 and Month 13
16. At Day 1 (pre-vaccination) and Month 13
17. At Day 1, Month 2 and Month 13 |
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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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
No study vaccination, treatment according to local standard of care, including routine vaccination |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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Last testing results released of samples collected at Visit Month 13 |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |