E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 20.0 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10019972 |
E.1.2 | Term | Herpes viral infections |
E.1.2 | System Organ Class | 100000005073 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10047438 |
E.1.2 | Term | Viral infectious disorders |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
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 persistence of humoral and cell mediated immune responses overall at Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577). |
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E.2.2 | Secondary objectives of the trial |
For the persistence phase Months 108 and 120 post first dose of initial vaccination in study Zoster-003 (NCT00434577): • To evaluate the persistence of humoral and cell mediated immune responses within each age cohort (60-69 YOA and ≥70 YOA at the time of the initial vaccination) at Months 108 and 120 post first dose of initial vaccination course. • To evaluate the safety of the study vaccine from Month 108 to Month 120 post first dose of initial vaccination course.
For the re-vaccination phase: • To evaluate humoral and cell mediated immune responses to a two dose re-vaccination course at one month after each dose (Months 121 and 123) and 12 months after last dose (Month 134) when administered 10 years after the initial vaccination course. • To evaluate the reactogenicity and safety of the study vaccine after re-vaccination with two additional doses. |
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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 (e.g., completion of the diary cards, return for follow-up visits, ability to have scheduled contacts to allow evaluation during the study). Or subjects with a care-giver who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, vaccination visits, availability for follow-up contacts). • Written informed consent obtained from the subject prior to performance of any study specific procedure. • Previous participation in study ZOSTER-003 (NCT00434577), in group 50 µg gE / AS01B, and who completed the vaccination course (2 doses of HZ/su) in study ZOSTER-003 (NCT00434577). • Subjects are expected to enter the study (or complete Visit 1) as of the time they turn 108 months after first vaccination of previous vaccination course with HZ/su and not later than 111 months. |
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E.4 | Principal exclusion criteria |
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine during the period starting 30 days before the first study visit (Day -29 to Day 0), or planned use during the study period. • 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 (>14 consecutive days of prednisone at a dose of ≥20 mg/day [or equivalent]), long-acting immune-modifying agents (e.g., infliximab) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders). • Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection). • 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* within 8 days prior to or within 14 days after either dose of study vaccine. *E.g., inactivated and subunit vaccines, including inactivated and subunit influenza vaccines and pneumococcal conjugate vaccines. • Previous vaccination against HZ since initial vaccination in Zoster-003. • Administration of immunoglobulins and/or any blood products during the period starting 3 months before the study start, or planned administration during the study period. • History of previous HZ. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Antigen-specific antibody (Ab) concentrations. - Anti-gE Ab concentrations as determined by ELISA 2. Cell-Mediated Immunity (CMI) in terms of frequencies of anti-gen-specific CD4 T-cells. - Frequencies of CD4+ T cells with antigen-specific Interferon gamma (IFN-γ) and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-α) and/or CD40 Ligand (CD40L) secretion/expression to gE as determined by Intracellular Cytokine Staining (ICS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 and 2. At Month 108 and Month 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577). |
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E.5.2 | Secondary end point(s) |
1. Antigen-specific antibody (Ab) concentrations. - Anti-gE Ab concentrations as determined by ELISA within each age cohort (60-69 YOA and ≥70 YOA at the time of initial vaccination) 2. Cell-Mediated Immunity (CMI) in terms of frequencies of anti-gen-specific CD4 T-cells. - Frequencies of CD4+ T cells with antigen-specific Interferon gamma (IFN-γ) and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-α) and/or CD40 Ligand (CD40L) secretion/expression to gE as determined by Intracellular Cytokine Staining (ICS) within each age cohort (60-69 YOA and ≥ 70 YOA at the time of initial vaccination) 3. Occurrence of all serious adverse events (SAEs) related to study participation or to a concurrent GSK medication/vaccine (including HZ/su administered during the Zoster-003 (NCT00434577) study). - Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. 4. Antigen-specific antibody (Ab) concentrations post re-vaccination. - Anti-gE antibody concentrations as determined by ELISA in all subjects 5. Cell-Mediated Immunity (CMI) in terms of frequencies of anti-gen-specific CD4 T- cells - Frequencies of CD4+ T cells with antigen-specific Interferon gamma (IFN-γ) and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-α) and/or CD40 Ligand (CD40L) secretion/expression to gE as determined by Intracellular Cytokine Staining (ICS) 6. Occurrence and intensity of each solicited local and general symptom in all subjects 7. Occurrence, intensity and relationship to vaccination of unsolicited AEs according to the Medical Dictionary for Regulatory Activities (MedDRA) classification in all subjects - An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, every-day activities. Related = AE assessed by the investigator as related to the vaccination. 8. Occurrence and relationship to vaccination of all SAEs Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. 9. Occurrence of any fatal SAEs - Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. 10. Occurrence and relationship to vaccination of any pIMDs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 and 2. At Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577). 3. Between Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577). 4 and 5. At 1 month post each vaccination dose, and at 12 months after the last vaccination dose in current study (corresponding to 121, 123 and 134 months post first dose of initial vaccination course in study Zoster-003 (NCT00434577)). 6. Within 7 days (Days 0-6) after each vaccination in the current study 7. During 30 days (Days 0-29) after each vaccination in the current study 8, 9 and 10. From Dose 1 of re-vaccination until study end at 14 months after the last dose of the vaccination in the current study |
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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 | 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 | No |
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 | No |
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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 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 | 9 |
E.8.9.1 | In the Member State concerned days | 17 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 17 |