E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 the heat-treated varicella-zoster vaccine (VZV) vaccine in recipients of autologous hematopoietic cell transplant (HCT).
To assess the impact of the heat-treated 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 the heat-treated VZV vaccine on the development of postherpetic neuralgia (PHN) [defined as a worst pain in the last 24 hours of 3 or greater (on a 0-to-10 scale) on the Zoster Brief Pain Inventory (ZBPI)] that persists or appears more than 90 days after the onset of the HZ rash] post-autologous HCT.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient is ≥18 years of age on day of signing informed consent. Patient has prior history of varicella, antibodies to VZV (documented prior to receipt of blood products), or residence in a country with endemic VZV infection for ≥30 years or if patient is 30 years old, attended primary or secondary school in a country with endemic VZV infection. Patient is scheduled to undergo autologous HCT for treatment of lymphoma or non-lymphoma cancer (i.e., any other malignancy) within 60 days of enrolment.
Patient is highly unlikely to conceive during the time period starting 2 weeks prior to enrollment through 6 months from last vaccination dose, as indicated by at least one “yes” answer to the following questions: Patient is a male. Patient is a surgically sterilized female. Patient is a postmenopausal female. Postmenopausal status is defined as ≥43 years of age and 1) no menses for >1 year but <3 years and confirmed by follicle stimulating hormone (FSH) levels elevated into the postmenopausal range or 2) no menses for at least 3 years. Patient is a nonsterilized premenopausal female who is not heterosexually active (and does not plan to become heterosexually active for the duration of the study) or is willing to use 2 adequate barrier methods of contraception to prevent pregnancy throughout the study, starting at least 2 weeks prior to enrollment.
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E.4 | Principal exclusion criteria |
Patient has a history of hypersensitivity reaction to any vaccine component, including gelatin or neomycin (a history of contact dermatitis to neomycin is not a criterion for study exclusion). Patient has a prior history of HZ within 1 year of enrollment. Patient has a prior history of receipt of any varicella or zoster vaccine. Patient has a cancer other than Hodgkin’s lymphoma and has had more than 2 relapses of the underlying cancer. Patient is expected to undergo a tandem transplant procedure. Patient is pregnant or breastfeeding or expecting to conceive within the period of 2 weeks prior to enrollment through 6 months from last vaccination dose. Patient has received a live virus vaccine or is scheduled to receive a live virus vaccine in the period from 4 weeks prior to Dose 1 through 28 days Postdose 4. Patient has received an inactivated vaccine or is scheduled to receive an inactivated vaccine in the period between 7 days prior to and 28 days following Dose 1.
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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. Blood samples will be collected from all patients to test for VZV-specific antibody responses as measured by gpELISA prior to Dose 1 (the pre-HCT dose), as well 60 days (prior to Dose 3), 90 days (prior to Dose 4), 120 days, 6 months, 12 months, 18 months and 24 months after HCT and annually thereafter until study completion. The primary safety endpoint of the study will be safety and tolerability following all 4 vaccine doses and will be based on the incidence of vaccine-related serious adverse experiences observed during the four 28-day follow-up periods in each vaccination group.
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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 |
Tolerability and Immunogenicity |
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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 | 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 | 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.8.4.1 | 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 | 6 |
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 |
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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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The study will continue until ~200 confirmed cases of herpes zoster (HZ) have accrued, or when the decision is made to stop the study earlier based on the recommendations of the Data Safety Monitoring Board (DSMB) if the results of the interim analysis indicate the vaccine is effective. When the required number of confirmed HZ cases has accrued, the study will enter the close-out phase. |
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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 | 3 |
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 | 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 |