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 | 17.0 |
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 demonstrate lot-to-lot consistency in terms of anti-gE humoral immunogenicity between three production lots of the HZ/su vaccine one month after the second dose (Month 3). |
|
E.2.2 | Secondary objectives of the trial |
- To demonstrate the consistency of three manufacturing lots of HZ/su vaccine in terms of vaccine response rates one month after the second vaccine dose.
Criteria:
For each pair-wise comparison, the two-sided 95% confidence interval (CI) on the lot difference in vaccine response rate (VRR) to the HZ/su vaccine (in terms of the humoral anti-gE immune response) one month after the second vaccine dose is within the [-10%; +10%] margin.
This secondary objective will be assessed in a hierarchical manner i.e. it can only be met if the statistical criteria for this objective are met as well as the statistical criteria for the primary objective.
- To characterize anti-gE humoral immune responses for all study groups at Month 0 and Month 3.
- To evaluate the safety and reactogenicity following administration of HZ/su vaccine up to one month post last vaccination and until study end (Month 14). |
|
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 50 years or older at the time of the first vaccination.
- Written informed consent obtained from the subject.
- Female subjects of non-childbearing potential may be enrolled in the study.
* Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy 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 during the entire treatment period and for 2 months after completion of the vaccination series.
• Female subjects of childbearing potential may be enrolled in the study, if the subject: |
|
E.4 | Principal exclusion criteria |
- Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
- Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. A prednisone dose of <20 mg/day is allowed. Inhaled, topical and intra-articular corticosteroids are allowed.
- Administration or planned administration of a live vaccine in the period starting 30 days before 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 (E.g. inactivated and subunit vaccines) within 8 days prior to or within 14 days after either dose of study vaccine.
- Administration of long-acting immune-modifying drugs within six months prior to the first vaccine dose or expected administration at any time during the study period.
- 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 product.
- Previous vaccination against HZ or varicella.
- Planned administration during the study of an HZ or varicella vaccine other than the study vaccine.
- History of HZ.
- Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy.
- 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.
* 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.
- Administration of immunoglobulins and/or any blood products within 3 months preceding the first dose of study vaccine or planned administration during the study period.
- Pregnant or lactating females.
- Females planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 4
- Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.
- Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study
- Any condition which, in the judgment of the investigator would make intramuscular injection unsafe. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Anti-gE humoral immunogenicity.
* Anti-gE antibody concentrations, as determined by enzyme-linked immunosorbent assay (ELISA). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Anti-gE antibody concentrations at Month 3. |
|
E.5.2 | Secondary end point(s) |
- Anti-gE humoral immunogenicity.
* Anti-gE antibody concentrations, as determined by ELISA.
* Vaccine response for anti-gE humoral immunogenicity, as determine 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 Medical Dictionary for Regulatory Activities (MedDRA) classification.
- Occurrene of Serious Adverse Events (SAEs)
* Occurrence and relationship to vaccination of all SAEs.
- Occurrence of AEs of specific interest.
* Occurrence of any potential Immune Mediated Diseases (pIMDs). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Anti-gE antibody concentrations at Month 0 and Month 3.
- Vaccine response for anti-gE humoral immunogenicity at Month 3.
- 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 first vaccination up to 30 days post last vaccination (Month 0-Month 3).
* From 30 days post last vaccination until study end (Month 4 - Month 14).
- pIMDs:
* From first vaccination up to 30 days post last vaccination. (Month 0-Month 3)
* During the period starting after 30 days post last vaccination until study end. (Month 4 –Month 14) |
|
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 | Yes |
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 |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 20 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 20 |