E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers (Prevention of Herpes Zoster) |
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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 compare the incidence of HZ recurrence in the HZ/su group to the placebo group
A formal non-inferiority analysis will be performed.
Criterion: The objective is met if the upper limit (UL) of the 95% CI of the ratio of the incidence of HZ recurrence (HZ/su versus placebo) is below 5.
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E.2.2 | Secondary objectives of the trial |
•To evaluate the rate of HZ recurrence in HZ/su and placebo groups during the entire study period.
•To evaluate safety and reactogenicity following administration of HZ/su vaccine or placebo within 30 days after each dose.
•To evaluate safety following administration of HZ/su vaccine or placebo during the entire study period.
•To characterize anti-gE humoral immunogenicity response prior to the first vaccination (Day 1), at two months post first vaccination (Month 2) and at one month post last vaccination (Month 3) in both groups.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subjects and/or subject’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/subject’s LAR(s) prior to performance of any study specific procedure.
•A male or female ≥ 50 YOA at the time of the first vaccination.
•Subjects with a history of HZ. Confirmation of the prior HZ diagnosis can be done by one of the following three methods:
Clinically diagnosed HZ OR Laboratory diagnosed HZ OR HZ diagnosed by an adjudication committee
Female subjects of non-childbearing potential may be enrolled in the study.
(Non-childbearing potential is defined as current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy, bilateral salpingectomy or post-menopause).
•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 vaccination, and
has agreed to continue adequate contraception for 2 months after completion of the vaccination series.
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E.4 | Principal exclusion criteria |
•Subjects who at time of study entry or during the maximum period of anticipated study participation are/will become part of the population recommended to receive a zoster vaccine per existing local or national immunization practices will be excluded from study participation.
•Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period.
•Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
•Onset of HZ in the past 6 months or any ongoing symptoms from a prior HZ episode.
•Chronic antiviral use for HZ prophylaxis.
•History of >1 prior episode of HZ.
•A history of disseminated HZ, cutaneous or associated with visceral disease or associated with neurologic disease caused by VZV infection.
•Use or anticipated use of immunosuppressants or immune-modifying drugs during the period starting six months prior to study start and during the whole study period. This includes chronic administration of corticosteroids, long-acting immune-modifying agents or immunosuppressive/cytotoxic therapy
•Administration or planned administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine. However, licensed pneumococcal vaccines and non-replicating vaccines may be administered up until 8 days prior to dose 1 and/or dose 2 and/or at least 14 days after any dose of study vaccine.
•Concurrently participating 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 vaccine/product
•Previous vaccination against VZV or HZ.
•Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
•Acute disease and/or fever at the time of enrolment.
•Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
•Pregnant or lactating female.
•Female planning to become pregnant or planning to discontinue contraceptive precautions in the period up to 2 months after completion of the vaccination series.
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of confirmed Herpes Zoster (HZ) cases.
A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis.
A suspected case of HZ is confirmed by 2 ways:
• By PCR (Polymerase Chain Reaction)
• By the HZ Ascertainment Committee (HZAC)
The incidence of HZ recurrence in the HZ/su group versus placebo group is compared by performing a non-inferiority analysis.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From one-month post-dose 2 to study end (Month 26)
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E.5.2 | Secondary end point(s) |
Number of confirmed HZ cases
Number of subjects with any solicited local adverse events (AEs)
Number of subjects with any solicited general AEs
Number of subjects with any unsolicited AEs
Number of subjects with any serious adverse events (SAEs)
Number of subjects with any serious adverse events (SAEs)
Number of subjects with any related SAEs
Number of subjects with any potential immune-mediated diseases (pIMDs)
Number of subjects with any pIMDs
Vaccine response rate (VRR) for anti-glycoprotein E (Anti-gE) antibodies as determined by Enzyme Linked Immuno-sorbent Assay (ELISA)
Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs) as determined by ELISA |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From Visit Day 1 till study end (Month 26)
Within 7 days (Days 1-7) after each vaccination
Within 7 days (Days 1-7) after each vaccination
Within 30 days (Days 1-30) after each vaccination
From Visit Day 1 up to 30 days post last vaccination
From 30 days post last vaccination to 1 year post last vaccination.
During the entire study period (Visit day 1 to Month 26)
From Visit Day 1 up to 30 days post last vaccination
From 30 days post last vaccination to 1 year post last vaccination
At Month 2 and Month 3
At Day 1, Month 2 and Month 3 |
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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) | 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 |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Hong Kong |
Mexico |
Panama |
Russian Federation |
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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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After all the subjects complete their study conclusion contact, occurring within 30 days of the projected study conclusion date of the late enrolled subject, that is, 26 months (790 days) from the enrolment date of the last subject AND the release of all polymerase chain reaction (PCR) test results for the HZ rash lesion samples |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |