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 |
|
E.1.1.1 | Medical condition in easily understood language |
Incidence of Herpes Zoster in adults with solid tumor |
|
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 |
|
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 V212 (inactivated VZV vaccine) in adults with solid tumor (STM) and to assess the impact of inactivated VZV vaccine on the development of herpes zoster (HZ) in adults with solid tumor. |
|
E.2.2 | Secondary objectives of the trial |
To assess the impact of V212 on the development of
- moderate to severe HZassociated pain at any time from HZ onset through the end of the 6 month HZ followup
period.
- 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.
- postherpetic neuralgia (PHN). |
|
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-gamma ELISPOT) assay. |
|
E.3 | Principal inclusion criteria |
1. Patient has been diagnosed with a solid tumor or hematologic malignancy AND is not likely to undergo hematopoietic cell transplant (HCT) and meets one of the criteria specified below.
- Is 18 years of age or older and is receiving a cytotoxic or immunosuppressive chemotherapy regimen
- Is 50 years of age or older with a hematologic malignancy, not in remission, regardless of whether the patient is or is not receiving chemotherapy
2. Life expectancy ≥ 12 months.
3. Signed an informed consent prior to any study procedures.
4. Patient has prior history of varicella, antibodies to VZV (documented prior to receipt of blood products), or residence (for ≥30 years) in a country with endemic VZV infection, or if participant is 30 years old, attended primary or secondary school in a country with endemic VZV infection (see Section 3.2.8 for more details).
5. All female patients of childbearing potential (as defined below under #7) must have a negative serum or urine pregnancy test (sensitive to 25IU β-hCG).
6. 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":
- Patient is male.
- Patient is female who agrees to remain abstinent or use (or have their partner use) adequate contraception during the time period starting 2 weeks prior to enrollment through 6 months from the last vaccination dose. Note that simultaneous use of two reliable forms of contraception is recommended.
- Patient is a female who is not of reproductive potential. A female patient who is
not of reproductive potential is defined as: one who has either (1) reached natural
menopause (defined as 6 months of spontaneous amenorrhea with serum follicle
stimulating hormone [FSH] levels in the postmenopausal range as determined by
a laboratory, or 12 months of spontaneous amenorrhea), (2) post-surgical bilateral
oophorectomy and/or hysterectomy, or (3) bilateral tubal ligation.
7. Patients with STM will be eligible for enrollment if they have not received (nor are expected to require receipt of) blood products within 3 months prior to enrollment through 28 days Postvaccination 4. |
|
E.4 | Principal exclusion criteria |
1. A history of allergic reaction to any vaccine component (including gelatin) or an anaphylactic/anaphylactoid reaction to neomycin (a history of contact dermatitis to neomycin is not a criterion for study exclusion).
2. Prior history of HZ within 1 year of enrollment.
3. Prior or expected receipt of any varicella or non-study zoster vaccine.
4. Patient is currently receiving or expected to receive long-term antiviral prophylaxis (greater than 4 weeks duration) with activity against herpes simplex virus (HSV),VZV or cytomegalovirus (CMV).
5. Patient is pregnant or breastfeeding or expecting to conceive within the period of 2 weeks prior to enrollment throughout 6 months after last vaccination dose.
6. Any live virus vaccine administered or scheduled in the period from 4 weeks prior to Dose 1 through 28 days postvaccination dose 4.
7. Any inactivated vaccine administered or scheduled within the period from 7 days prior to, through 7 days following, any dose of study vaccine.
8. Patients with STM will be excluded from the ELISPOT substudy if they have received (or are expected to require receipt of) blood products within 3 months prior to enrollment through 28 days Postvaccination 4. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: incidence of HZ in the vaccine and placebo groups in the STM population
Safety: Incidence of serious adverse experiences following 4 doses of vaccination for the STM-population
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy: number of HZ cases per 1000 person-years of follow-up from study enrollment to the end of study.
Safety: Vaccination Day 1 through 28 days Postdose 4
|
|
E.5.2 | Secondary end point(s) |
- incidence of moderate to severe HZ-associated pain
- composite efficacy endpoint of the incidence of HZ complications during the study
-the incidence of PHN |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Entire duration of the study
|
|
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 |
|
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.8.2.4 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Colombia |
Croatia |
Czech Republic |
Ecuador |
Estonia |
France |
Germany |
Greece |
Honduras |
Hong Kong |
India |
Italy |
Korea, Republic of |
Lebanon |
Lithuania |
Mexico |
New Zealand |
Panama |
Peru |
Philippines |
Romania |
Russian Federation |
Saudi Arabia |
Singapore |
Slovakia |
South Africa |
Spain |
Taiwan |
Thailand |
Turkey |
United Arab Emirates |
United Kingdom |
United States |
Jordan |
Venezuela, Bolivarian Republic of |
|
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
|
Accrual of the required number of confirmed HZ cases (approx. 232)
|
|
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 |