E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vaccination against HZ and its related complications in adults older than 50 years |
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E.1.1.1 | Medical condition in easily understood language |
Herpes zoster (Shingles) disease |
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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 | 14.1 |
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 |
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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-glyoprotein E (gE) humoral immune responses at one 1 month (mth) post-dose 2 (PD2) in the 0,6-mth and 0,12-mth schedule groups.
*Criterion:The lower limit of the 97,5% confidence interval (CI) of the VRR for anti-gE ELISA antibody concentrations at 1 mth PD2 in the 0,6-mth or 0,12-mth schedule groups is at least 60%
If the objectives are met for the 0,6-mth and 0,12-mth schedules, the following objective will be evaluated:
-Non-inferiority in terms of anti-gE humoral immune response 1 mth PD2 given according to a 0,6-mth schedule compared to a 0,2-mth schedule and a 0,12-mth schedule compared to a 0,2-mth schedule
Criteria for non-inferiority:
*The upper limit of the 97,5% CI for the anti-gE ELISA geometric mean concentration (GMC) ratio (0,2-mth schedule over 0,6-mth schedule) at 1 mth PD2 is <1.5
*The upper limit of the 97,5% CI for the anti-gE ELISA GMC ratio (0,2-mth schedule over 0,12-mth schedule) at 1 mth PD2 is <1.5 |
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E.2.2 | Secondary objectives of the trial |
- To characterise anti-gE humoral immune responses for all study groups at all sampling time points.
- To evaluate the safety and reactogenicity following administration of HZ/su vaccine up to one month post last vaccination, and during the whole follow-up period. |
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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 two months after completion of the vaccination series. |
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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. For corticosteroids, a prednisone dose of < 20 mg/day, or equivalent, 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 and ending 30 days after either dose of study vaccine.
- Administration or planned administration of a non-replicating vaccine within eight days prior to or within 14 days after either dose of study vaccine.
- Administration of long-acting immune-modifying drugs (e.g. infliximab) within six months prior to the first vaccine dose or expected administration at any time during the study period.
- Previous vaccination against varicella or HZ (either registered product or participation in a previous vaccine study).
- Planned administration during the study of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine.
- History of HZ.
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
- Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g. malignancy, human immunodeficiency virus [HIV] infection) or immunosuppressive/cytotoxic therapy (e.g. medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).
- Acute disease and/or fever at the time of enrolment.
*Fever is defined as temperature ≥ 37.5°C (99.5°F) for oral, axillary or tympanic route, or ≥ 38.0°C (100.4°F) for rectal route. The preferred route for recording temperature in this study will be oral.
*Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
- Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
- Significant underlying illness that, in the opinion of the investigator, would be expected to prevent completion of the study.
- Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study.
- Pregnant or lactating female.
- Female planning to become pregnant during the entire treatment period and for two months after completion of the vaccination series, or planning to discontinue contraceptive precautions (if of childbearing potential). |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Anti-gE humoral immunogenicity in terms of antibody concentration:
*Vaccine response for anti-gE humoral immunogenicity, as determined by ELISA
*Anti-gE antibody concentrations, as determined by ELISA in all subjects
The VRR for anti-gE is defined as the percentage of subjects who have at least:
*a 4-fold increase in the anti-gE antibodies concentration as compared to the pre vaccination anti-gE antibodies concentration, for subjects who are seropositive at baseline, or
*a 4-fold increase in the anti-gE antibodies concentration as compared to the anti gE antibodies cut-off value for seropositivity for subjects who are seronegative at baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Anti-gE humoral immunogenecity in terms of antibody concentrations:
*Anti-gE antibody concentrations as determined by ELISA in all subjects
- 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 AEs according to the Medical Dictionary for Regulatory Activities (MedDRA) classification
- Occurrence 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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Anti-gE humoral immunogenecity in terms of antibody concentrations: at Month 0, 3, 7, 13, 14, 18, 24 (depending on group)
- Solicited symptoms: within 7 days (Days 0 to 6) after each vaccination
- Unsolicited symptoms: during 30 days (Days 0 to 29) after each vaccination
- SAEs: from first vaccination until study end (Month 14, 18 and 24, depending on group)
- AEs of specific interest: from first vaccination until study end (Month 14, 18 and 24, depending on group) |
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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 | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 1 |
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 |
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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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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 | 5 |
E.8.9.1 | In the Member State concerned days | 29 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 29 |