E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Incidence of Herpes Zoster in recipients of Autologous HCTs |
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E.1.1.1 | Medical condition in easily understood language |
Incidence of Herpes Zoster in Recipients of Autologous Hematopoietic Cell Transplants |
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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 | 16.1 |
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 assess the safety and tolerability of inactivated VZV vaccine in recipients of autologous HCT and to assess the impact of inactivated VZV vaccine on the development of HZ following autologous HCT |
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E.2.2 | Secondary objectives of the trial |
To assess the impact of inactivated VZV vaccine on: 1) the development of moderate to severe HZ-associated pain at any time from HZ onset through the end of the 6 month HZ follow-up period, 2) the development of HZ complications, and 3) the development of PHN. |
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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 |
IFN-γ ELISPOT substudy will enroll a subset of patients (~420 patients of the total ~1200) to measure immune responses measured by interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay.
In the Netherlands, all patients will participate in the substudy. |
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E.3 | Principal inclusion criteria |
Patient is >18 years of age who 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 coutry with endemic VZV infection) who is scheduled to undergo an autologous HCT for treatment of lymphoma or other indication (malignancy or an indication that is not malignancy) within 60 days of enrolment. |
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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, or has had more than 2 relapses of their underlying cancer (If the patient’s underlying cancer is Hodgkin’s lymphoma, more than 2 relapses are permitted). Patients expected to undergo a tandem transplant procedure or expected to receive >6 months (>180 days) of prophylactic antiviral therapy post-HCT. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary clinical efficacy endpoint will be the incidence of HZ. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Event-Driven study relying on the accrual of ~252 confirmed HZ cases
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E.5.2 | Secondary end point(s) |
To assess the impact of inactivated VZV vaccine on the development of moderate to severe HZ-associated pain at any time from HZ onset through the end of the 6 month HZ follow-up period. Moderate to severe HZ-associated pain is defined as 2 or more occurrences of a score of 3 or greater (0-to-10 scale) on the Zoster Brief Pain Inventory (ZBPI) post-autologous HCT.
To assess the impact of inactivated VZV vaccine 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 post-autologous HCT.
To assess the impact of inactivated VZV vaccine on the development of PHN. PHN is defined as pain in the area of the HZ rash with a pain in the last 24 hours score of 3 or greater (on a 0 to 10 scale) on the ZBPI that persists or appears greater than or equal to 90 days after HZ rash onset post-autologous HCT
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Event-Driven study relying on the accrual of ~252 confirmed HZ cases
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Belgium |
Canada |
France |
Italy |
Austria |
Croatia |
Netherlands |
Portugal |
Sweden |
Argentina |
Brazil |
Colombia |
Czech Republic |
Ecuador |
Germany |
Korea, Democratic People's Republic of |
Lithuania |
Puerto Rico |
Spain |
Israel |
Mexico |
Panama |
Peru |
Russian Federation |
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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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 | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |