E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Incidence of Herpes Zoster in adults with solid tumor or hematologic malignancy |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.1 |
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 |
1. To assess the safety and tolerability of V212 when administered to adults with STM.
2. To assess the impact of V212 on the development of HZ in adults with STM. |
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E.2.2 | Secondary objectives of the trial |
1. To assess the impact of V212 on the development of moderate to severe HZ-associated pain at any time from HZ onset through the end of the 6-mnth HZ follow-up period. Moderate to severe HZ-associated pain is defined as 2 or more occurrences of a score of 3 or greater on the Zoster Brief Pain Inventory (ZBPI).
2. To assess the impact of V212 on the development of HZ complications defined as the occurrence of any of the following during the study: hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, or administration of intravenous acyclovir therapy for treatment of HZ.
3. To assess the impact of V212 on the development of PHN. PHN is defined as a worst pain score (in the previous 24 hr) of 3 or greater on the ZBPI, that persists or appears greater than or equal to 90d after the onset of HZ rash.
The above objectives will be evaluated for STM only. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ELISPOT substudy will enroll a subset of patients (~1000 patients of the total ~5264) to measure immune response by interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay. |
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E.3 | Principal inclusion criteria |
Patient is ≥18 years of age with a solid tumor or hematologic malignancy receiving immunosuppressive or cytotoxic chemotherapy, has a prior history of varicella, antibodies to VZV, or residence in a country with endemic VZV infection for >30 years (if patient is <30 years old, attended primary or secondary school in a country with endemic VZV infection), is not likely to undergo hematopoietic cell transplant, and has not/will not be treated with rituximab in the time period from 3 months prior to enrollment through 28 days following the last dose of study vaccine, is not likely to received long-term antiviral prophylaxis of greater than 4 weeks duration, with activity against VZV, cytomegalovirus or herpes simplex virus.
Patient is ≥50 years of age with a hematologic malignancy not in remission, may or may not be receiving chemotherapy, has a prior history of varicella, antibodies to VZV, or residence in a country with endemic VZV infection for >30 years, is not likely to undergo hematopoietic cell transplant, and has not/will not be treated with rituximab from 3 months prior to enrolment through 28 days following the last dose of study vaccine is not likely to received long-term antiviral prophylaxis of greater than 4 weeks duration, with activity against VZV, cytomegalovirus or herpes simplex virus.
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E.4 | Principal exclusion criteria |
Patient has a prior history of HZ within 1-year of enrolment, a prior history of receipt of any varicella or zoster vaccine, is likely to undergo hematopoietic cell transplant, and has been treated with rituximab or is expected to be treated with rituximab in the period from 3 months prior to enrolment through 28 days following the last dose of study vaccine and is likely to receive long term antiviral prophylaxis (greater than 4 weeks duration) with activity against varicella-zoster virus zoster, cytomegalovirus, or herpes simplex virus. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary clinical efficacy endpoint is the incidence of herpes zoster. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study will use an adaptive design based on pre-specified criteria, using an independent, external Data Monitoring Committee to monitor safey and efficacy. The study will be conducted based on 2 key efficacy milestones:
- When at least 50% of the required confirmed HZ cases accrued for each population, HM and STM, interim futility analysis will be done for each group (completed 29Oct2014).
- When 90 confirmed HZ cases accrued in STM population, the database will be unblinded, the final efficacy analysis will be done. NB! if observed HZ case accrual rate indicates that more than 5 yrs of patient follow-up (FU) will be necessary to accrue targeted number of confirmed cases, then SPONSOR will consider it beyond adjustment cap and terminate study after appr. 5yrs of patient FU have occurred. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 |
immunogenic response to vaccine |
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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 | Yes |
E.8.1.5 | Parallel group | Yes |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Colombia |
Croatia |
Czech Republic |
Ecuador |
Estonia |
France |
Germany |
Greece |
Honduras |
Hong Kong |
Italy |
Korea, Republic of |
Lebanon |
Lithuania |
Mexico |
New Zealand |
Panama |
Peru |
Philippines |
Puerto Rico |
Romania |
Russian Federation |
Saudi Arabia |
Singapore |
Slovakia |
South Africa |
Spain |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
Jordan |
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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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See Protocol 3.2.19 Study Completion Procedures |
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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 | 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 |