E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary immunization of subjects ≥ 70 YOA against Herpes Zoster (HZ). The study population includes males and females without severely immunocompromising conditions in the age ranges 70-79 YOA and ≥ 80 YOA. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019974 |
E.1.2 | Term | Herpes zoster |
|
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 |
* Co-primary Objectives for study ZOSTER-022 •To evaluate vaccine efficacy (VE) in the prevention of HZ compared to placebo in adults ≥ 70 YOA, as measured by the reduction in HZ risk; •To evaluate VE in the prevention of overall PHN compared to placebo in subjects ≥ 70 YOA.
*Primary objectives for pooled analysis of studies ZOSTER-006 (EudraCT nr 2008-000367-42; study 110390) and ZOSTER-022 •To evaluate VE in the prevention of overall PHN compared to placebo in subjects ≥ 50 YOA; •To consolidate VE estimation in the prevention of HZ compared to placebo in subjects ≥ 70 YOA across both phase III studies; •To consolidate VE estimation in the prevention of PHN compared to placebo in subjects ≥ 70 YOA across both phase III studies.
|
|
E.2.2 | Secondary objectives of the trial |
•To evaluate VE in reducing the total duration of severe ‘worst’ HZ-associated pain over the entire pain reporting period versus placebo (Pl) in subjects ≥70 YOA with confirmed HZ; •To evaluate VE in the reduction of overall and HZ-related mortality and hospitalizations versus Pl in subjects ≥70 YOA; •To evaluate VE in the reduction in incidence of HZ-associated complications versus Pl in subjects ≥70 YOA with confirmed HZ; •To evaluate VE in the reduction in use of pain medications versus Pl in subjects ≥70 YOA with confirmed HZ; •To evaluate vaccine safety and reactogenicity. *ZOSTER-006 and 022 pooled analysis: •To evaluate VE in the prevention of PHN versus Pl in subjects ≥50 YOA with confirmed HZ; •To evaluate VE in reducing the total duration of severe ‘worst’ HZ-associated pain over the entire pain reporting period versus Pl in subjects ≥70 YOA with confirmed HZ; •To evaluate vaccine safety and reactogenicity in subjects ≥ 70YOA.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subjects who the investigator believes will comply with the requirements of the protocol (e.g. completion of the diary cards/questionnaires, return for follow-up visits, have regular contact to allow evaluation during the study); •Written informed consent obtained from the subject; •A male or female aged 70 years or older at the time of the first vaccination.
|
|
E.4 | Principal exclusion criteria |
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use 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 (pharmaceutical product or device); •Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, HIV infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders); •History of HZ; •Previous vaccination against varicella or HZ (either registered product or participation in a previous vaccine study, and including previous vaccination with childhood varicella vaccine); •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Additionally, consider allergic reactions to other material or equipment related to study participation (such as materials that may possibly contain latex -gloves, syringes, etc). Please note, the vaccine and vials in this study do not contain latex; •Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to less than 4 years); •Receipt of immunoglobulins and/or any blood products within the 90 days preceding the first dose of study vaccine or planned administration during the study period; •Administration or planned administration of any other immunizations within 30 days before the first or second study vaccination or scheduled within 30 days after study vaccination. However, licensed non-replicating vaccines (i.e., inactivated and subunit vaccines, including inactivated and subunit influenza vaccines for seasonal or pandemic flu, with or without adjuvant) may be administered up to 8 days prior to each dose and/or at least 14 days after any dose of study vaccine; •Any other condition (e.g., extensive psoriasis, chronic pain syndrome, cognitive impairment, severe hearing loss) 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 enrolment; Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting, or ≥ 38.0°C (100.4°F) on rectal setting. 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. •Chronic administration (defined as more than 15 consecutive days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone < 20 mg/day, or equivalent, is allowed. Inhaled and topical steroids are allowed.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
•Confirmed HZ cases: Confirmed HZ cases during the study in the mTVc; •PHN cases: PHN cases in the mTVc. * For ZOSTER-006 and 022 pooled analysis: •Occurrence of overall PHN: Incidence of PHN calculated using the mTVc during the entire study period in subjects ≥50 YOA; •Occurrence of confirmed HZ: Occurrence of confirmed HZ during the entire study period in subjects ≥70 YOA; •Occurrence of overall PHN: Incidence of PHN calculated using the mTVc during the entire study period in subjects ≥70 YOA.
|
|
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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
reactogenicity, immunogenicity |
|
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 122 |
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 | Information not present in EudraCT |
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 | 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
|
Last subject last contact. Study end will take place when both conditions for final analysis are met and a minimum 90 days follow-up is completed for each HZ case that occurs up to the cut-off date for final analysis.
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 | 0 |