E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vaccination against HZ in adults with haematologic malignancies. |
|
E.1.1.1 | Medical condition in easily understood language |
Vaccination against shingles in adults with blood cancers. |
|
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 | 20.0 |
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 |
|
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 the safety and reactogenicity following administration of
the HZ/su vaccine compared to placebo from the first vaccination up to
30 days post last vaccination in subjects with haematologic
malignancies, aged 18 years and older.
- To evaluate vaccine response rate for anti-gE humoral immune
responses at Month 2 following a two-dose administration of the HZ/su
vaccine in subjects with haematologic malignancies excluding subjects
with Non-Hodgkin B-cell Lymphoma (NHBCL) and Chronic Lymphocytic
Leukaemia (CLL).
- To evaluate anti-gE humoral immune responses at Month 2 following a
two-dose administration of the HZ/su vaccine, as compared to placebo,
in subjects with haematologic malignancies excluding subjects with
NHBCL and CLL. |
|
E.2.2 | Secondary objectives of the trial |
In subjects with haematologic malignancies aged 18 years and older:
- Evaluate safety following administration of HZ/su vaccine compared to
placebo: from 1st vaccination up to 6 months post vaccination in at least
50% of the total vaccinated cohort, and, from 30 days post vaccination
until study end.
- Evaluate anti-gE humoral immune responses at Month 2 following two
doses of the HZ/su vaccine: compared to placebo, excluding subjects
with NHBCL; and VRR, excluding subjects with NHBCL.
- Evaluate incidence of confirmed HZ cases.
- Characterize anti-gE humoral immune responses at Month 0, 1, 2 and
13 within HZ/su and placebo groups by underlying disease strata.
- Characterize gE-specific CD4+ T-cell mediated immune responses at
Month 0, 1, 2 and 13 within HZ/su and placebo groups in the CMI subcohort
and by underlying disease strata.
- Assess correlation of HZ/su vaccine-induced humoral immune
responses with protection against HZ. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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;
- Subject who has been diagnosed with one or more haematologic malignancies prior to the first vaccination and who is receiving, is scheduled to receive or has just finished immunosuppressive cancer therapy to treat this condition;
- Life expectancy greater than or equal to 12 months, as assessed by the investigator;
- Female subjects of non-childbearing potential may be enrolled in the study;
For this study population, non-childbearing potential is defined as pre-menarche, 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, 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 2 months after completion of the vaccination series. |
|
E.4 | Principal exclusion criteria |
- Subject diagnosed with chronic lymphocytic leukaemia (CLL) who is receiving only oral cancer therapy (subject receiving intra-venous cancer therapy for CLL or intra-venous cancer therapy in combination with oral therapy may be enrolled);
- Subject receiving radiotherapy alone as treatment for his/her haematologic malignancy;
- Planned haematopoietic stem cell transplant (HCT) during the study period. (If a HCT occurred prior to enrolment in the study, the subject may not receive study vaccine until at least 50 days after the transplant procedure.);
- HIV infection by clinical history;
- Use of any investigational or non-registered product (drug or vaccine) 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 product to treat the subject’s 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 or varicella vaccine (including an investigational or non-registered vaccine) other 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 any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine;
- Administration or planned administration of a live vaccine in the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine;
- Administration or planned administration of a non-replicating vaccine* within 8 days prior to or within 14 days after either dose of study vaccine (* inactivated and subunit vaccines, including inactivated and subunit influenza vaccines and pneumococcal conjugate vaccines):
- Pregnant or lactating female;
- Female planning to become pregnant or planning to discontinue contraceptive precautions before Month 3 (i.e., 2 months after the last dose of study vaccine/placebo). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
* Occurrence of solicited local and general symptoms.
- Occurrence, intensity and duration of each solicited local symptom in
all subjects.
- Occurrence, intensity, duration and relationship to vaccination of each
solicited general symptom in all subjects.
* 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.
* Occurrence of serious adverse events (SAEs).
- Occurrence and relationship to vaccination of all SAEs in all subjects.
* Occurrence of AEs of specific interest.
- Occurrence and relationship to vaccination of any potential Immune-
Mediated Diseases (pIMDs) in all subjects.
* Anti gE humoral immunogenicity in all vaccinated subjects excluding
subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic
Leukaemia.
- Vaccine response for anti-gE humoral immunogenicity, as determined
by ELISA.
- Anti-gE antibody concentrations, as determined by ELISA. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Solicited symptoms: Up to 7 days (Days 0-6) after each vaccination
Unsolicited AEs: Up to 30 days (Days 0-29) after each vaccination
SAEs and AEs of specific interest: Up to 30 days post last vaccination
Anti-gE humoral immunogenicity: At Month 2 |
|
E.5.2 | Secondary end point(s) |
* Occurrence of SAEs
1. Occurrence and relationship to vaccination of all SAEs in at least 50%
of the total vaccinated cohort.
2. Occurrence and relationship to vaccination of all SAEs in all subjects.
* Occurrence of AEs of specific interest.
1. Occurrence of any pIMDs in at least 50% of the total vaccinated
cohort.
2. Occurrence of any pIMDs in all subjects.
* Anti gE humoral immunogenicity in all vaccinated subjects excluding
subjects with Non-Hodgkin B-cell Lymphoma.
- Vaccine response for anti-gE humoral immunogenicity, as determined
by ELISA.
- Anti-gE antibody concentrations, as determined by ELISA.
* Occurrence of confirmed HZ cases
* Anti-gE humoral immunogenicity in all vaccinated subjects.
1. Anti-gE antibody concentrations, as determined by ELISA.
2. Vaccine response for anti-gE humoral immunogenicity, as determined
by ELISA.
* gE-specific CD4+ T-cell-mediated immunogenicity response in the CMI
sub-cohort.
1. Frequencies of gE-specific CD4+ T-cells, expressing at least 2
activation markers (from among IFN-γ, IL-2, TNF-α and CD40L), as
determined by in vitro intracellular cytokine staining (ICS).
2. Vaccine response for gE-specific CD4+ T-cells expressing at least 2
activation markers (from among IFN-γ, IL-2, TNF-α and CD40L), as
determined by in vitro ICS
* Anti-gE humoral immunogenicity in subjects with confirmed HZ and
matched controls.
- Anti-gE antibody concentrations, as determined by ELISA. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
SAEs and AEs of specific interest:
1. From first vaccination up to 6 months post last vaccination,
2. From 30 days post last vaccination until study end
Anti-gE humoral immunogenicity excluding subjects with Non-Hodgkin
b-cell Lymphoma: At Month 2
HZ cases: From Month 0 until study end
Anti-gE humoral immunogenicity in all vaccinated subjects and CMI in
the CMI sub-cohort:
1. At Month 0, Month 1, Month 2 and Month 13,
2. At Month 1, Month 2 and Month 13
Anti-gE humoral immunogenicity in subjects with confirmed HZ cases
and matched controls: At Month 0 and at Month 2 |
|
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 | No |
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 |
|
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 |
|
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 | 42 |
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 |
Canada |
Czech Republic |
Finland |
France |
Hong Kong |
India |
Italy |
Korea, Republic of |
New Zealand |
Pakistan |
Panama |
Poland |
Russian Federation |
Singapore |
Spain |
Sweden |
Taiwan |
Turkey |
United Kingdom |
United States |
|
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
|
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 20 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 20 |