E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vaccination against herpes zoster (HZ) in adult autologous HCT recipients |
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E.1.1.1 | Medical condition in easily understood language |
Vaccination against shingles in adult recipients of autologous blood stem cells |
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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 | 18.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate VE in the prevention of HZ in autologous HCT recipients 18 years of age and older |
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E.2.2 | Secondary objectives of the trial |
•To evaluate VE in reducing the total duration of ‘worst’ HZ-associated pain over the entire pain reporting period in autologous HCT recipients 18 years of age and older with confirmed HZ;
•To evaluate VE in the reduction of confirmed HZ-associated complications in autologous HCT recipients 18 years of age and older;
•To evaluate VE in the prevention of Postherpetic Neuralgia (PHN) in autologous HCT recipients 18 years of age and older;
•To evaluate humoral immune responses to the study vaccine, when administered according to a 2-dose schedule in a sub-cohort of subjects;
•To evaluate vaccine safety and reactogenicity in autologous HCT recipients 18 years of age and older.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Study entry (enrolment) occurs at the Pre-vaccination visit.
•Subjects who the investigator believes can and will comply with the requirements of the protocol ;
•Written informed consent obtained from the subject;
•A male or female aged 18 years or older at the time of study entry.
•Has undergone or will undergo autologous HCT within 50-70 days prior to the first vaccination with the study vaccine/placebo, and there are no plans for additional HCTs;
•Female subjects of non-childbearing potential may be enrolled in the study;
For this study population, non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause.
OR
Female subjects of childbearing potential may be enrolled in the study, if the subject has practiced adequate contraception for 30 days prior to vaccination with the study vaccine/placebo, 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 12 months after completion of the vaccination series (i.e., until Month 13).
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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/placebo, or planned use during the study period. However, the investigational use of a registered or non-registered product to treat the subject’s underlying disease for which the HCT was undertaken, or a complication of the underlying disease, is allowed;
•Previous vaccination against HZ or varicella within the 12 months preceding the first dose of study vaccine/placebo;
•Planned administration during the study of a HZ vaccineother than the study vaccine;
•Occurrence of a varicella or HZ episode by clinical history within the 12 months preceding the first dose of study vaccine/placebo;
•History of allergic disease or reactions likely to be exacerbated by any component of the vaccine or study material and equipment;
•Prophylactic antiviral therapy with activity against Varicella Zoster Virus (VZV) expected to last more than 6 months after transplantation;
•Administration and/or planned administration of a vaccine not foreseen by the study protocol between HCT and 30 days after the last dose of study vaccine/placebo. However, licensed non-replicating vaccines may be administered up to 8 days prior to dose 1and/or 2, and/or at least 14 days after any dose of study vaccine/placebo;
•HIV infection by clinical history;
•Pregnant or lactating female;
•Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 13 (i.e., one year after the last dose of study vaccine/placebo).
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E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of confirmed HZ cases:
Incidence of confirmed HZ cases. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Month 0 until study end (4 years approximately) |
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E.5.2 | Secondary end point(s) |
1. Duration of ‘worst’ HZ-associated pain:Duration of HZ-associated pain rated as 3 or greater on the ‘worst pain’ Zoster Brief Pain Inventory (ZBPI) question, following the onset of a confirmed HZ rash over the entire pain reporting period in subjects with confirmed HZ.
2. Occurrence of confirmed HZ-associated complications: Incidence of confirmed HZ complications following the onset of HZ.
3. Occurrence of PHN: Incidence of PHN.
4. Antigen-specific Antibody (Ab) concentrations in a sub-cohort of subjects:Anti- gE Ab concentrations as determined by ELISA in a sub-cohort of subjects.
5. Occurrence of solicited local and general symptoms:-Occurrence and intensity of each solicited local symptom in all subjects
-Occurrence, intensity and relationship to vaccination of each solicited general symptom in all subjects.
6. Occurrence of unsolicited adverse events (AEs):Occurrence, intensity and relationship to vaccination of unsolicited AEs, according to the Medical Dictionary for Regulatory Activities (MedDRA) classification in all subjects.
7. Occurrence of Serious Adverse Events (SAEs):- Occurrence and relationship to vaccination of all SAEs in all subjects;
-Occurrence of SAEs related to the GSK study vaccine/placebo in all subjects;
-Occurrence of SAEs related to study participation or to a concurrent GSK medication/vaccine in all subjects;
-Occurrence of any fatal SAEs in all subjects.
8. Occurrence of AEs of specific interest:Occurrence of AEs of specific interest: -Occurrence and relationship to vaccination of any potential Immune Mediated Diseases (pIMDs)
-Occurrence of relapse cases in all subjects.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From Month 0 until study end (4 years approximately), from the onset of a confirmed HZ rash over the entire pain reporting period.
2. From Month 0 up until study end (4 years approximately.
3. From Month 0 until study end (4 years approximately).
4. At Month 0, Month 1, Month 2, Month 13 and Month 25.
5. Within 7 days (Days 0-6) after each vaccination.
6. During 30 days (Days 0-29) after each vaccination.
7. From the Pre-vaccination visit (Up to 110 days prior Month 0) until study end (4 years approximately).
8. From Month 0 until study end (4 years, approximately). |
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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 | 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 89 |
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 |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
Czech Republic |
Estonia |
Finland |
France |
Germany |
Greece |
Hong Kong |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Netherlands |
New Zealand |
Panama |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Taiwan |
Turkey |
United Kingdom |
United States |
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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
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Study end will take place when the conditions for final triggered analysis are met and follow-up is completed for each suspected HZ case that occurs up to the time that the study site is informed that the cut-off date for final analysis is established. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |