Immunogenicity and safety study of GlaxoSmithKline (GSK) Biologicals’ Herpes Zoster (HZ/su) vaccine in adults with solid tumours receiving chemotherapy.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2012-002966-11-GB
• Date of registration: 14/01/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: Immunogenicity and safety study of GlaxoSmithKline (GSK) Biologicals’ Herpes Zoster (HZ/su) vaccine in adults with solid tumours receiving chemotherapy.
• Scientific title: A phase II/III, randomised, observer-blind, placebo-controlled, multicentre, clinical trial to assess the immunogenicity and safety of GSK Biologicals’ herpes zoster HZ/su candidate vaccine when administered intramuscularly on a 0 and 1 to 2 months schedule to adults =18 years of age with solid tumours receiving chemotherapy. - ZOSTER-028
• Date of first enrolment: 13/02/2013
• Target sample size: 232
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002966-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Observer-blind; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Czech Republic, France, Korea, Republic of, Spain, United Kingdom

Contacts

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

Key inclusion & exclusion criteria

Inclusion criteria:
•Subjects who, in the opinion of the investigator, 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 (and has reached the age of legal consent) at the time of study entry (i.e., when informed consent is signed)
•Subject who has been diagnosed with one or more solid tumours (defined as a solid malignancy, i.e., not a blood element malignancy)
•Subject who is receiving or will receive a cytotoxic or immunosuppressive chemotherapy (such that the study vaccine can be administered at the latest at the start of the second cycle of chemotherapy)
•Life expectancy of greater than one year
•Female subjects of non-childbearing potential may be enrolled in the study;
-Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause;
•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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 142
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion criteria:
•Subjects receiving only newer, more targeted therapies if not taken together with a classical chemotherapy
•Chronic administration and/or planned administration of systemic glucocorticoids within one month prior to the first vaccine dose and up to Visit 3 (Month 2). Inhaled, intra-articularly injected, and topical steroids are allowed
•Previous vaccination against HZ or varicella within 12 months preceding the first dose of study vaccine/ placebo
•Planned administration during the study of a HZ vaccine (including an investigational or non-registered vaccine) other than the study vaccine
•Previous chemotherapy course less than one month before first study vaccination
•Occurrence of a varicella or HZ episode by clinical history within the 12 months preceding the first dose of study vaccine/ placebo
•History of allergic disease or reactions likely to be exacerbated by any component of the vaccine or study material and equipment
•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, or, administration or planned administration of a non-replicating vaccine within 8 days prior to or within 14 days after either dose of study vaccine.
•HIV infection by clinical history;
•Acute disease and/or fever at the time of vaccination. Acute disease is defined as the presence of a moderate or severe illness with or without fever, but excludes the underlying malignancy, as well as the expected symptoms/signs associated with that disease or its treatment;
-Fever is defined as temperature = 37.5°C /99.5°F on oral, axillary or tympanic setting, or = 38.0°C /100.4°F on rectal setting. The preferred route for recording temperature in this study will be oral.
-Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever, may receive the first dose of study vaccine/ placebo at the discretion of the investigator.
•Any condition which, in the judgment of the investigator would make intramuscular injection unsafe;
•Pregnant or lactating female;
•Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 3 (i.e., 2 months after the last dose of study vaccine/ placebo).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Herpes Zoster and related complications
MedDRA version: 17.0 Level: PT Classification code 10019974 Term: Herpes zoster System Organ Class: 10021881 - Infections and infestations
MedDRA version: 17.0 Level: HLT Classification code 10019972 Term: Herpes viral infections System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Herpes Zoster vaccine (GSK 1437173A)
Product Code: HZ/su
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: -
Current Sponsor code: gE
Other descriptive name: gE antigen
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Powder and solution for solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Secondary Objective: PreChemo groups only:
•To evaluate vaccine response rate (VRR) in anti-gE humoral immunogenicity responses at post-dose 2 of HZ/su vaccine (M2)
•To evaluate gE-specific CD4+ T-cell immunogenicity responses at post-dose 2 of HZ/su vaccine (M2), versus placebo (in CMI sub-cohort)
•To evaluate VRR in gE-specific CD4+ T-cell mediated immunogenicity at post-dose 2 of HZ/su vaccine (M2) (in CMI sub-cohort)
•To characterize gE-specific CD4+ T-cell mediated immunogenicity responses at M0, M1 and M13 (in CMI sub-cohort)

PreChemo and OnChemo groups:
•To evaluate the anti-gE humoral response at post-dose 2 of HZ/su vaccine (M2), versus placebo (all subjects)
•To evaluate VRR in anti-gE humoral immunogenicity responses at post-dose 2 of HZ/su vaccine (all subjects HZ/su)
•To evaluate safety following administration of HZ/su vaccine, versus placebo, from 30 days post last vaccination until study end
•To characterize anti-gE humoral immunogenicity responses at M0, M1, M2, M6 and M13

Timepoint(s) of evaluation of this end point: -At Month 2 (for A.)
Within 7 days (Days 0-6) after each vaccination (for B.)
-During 30 days (Days 0-29) after each vaccination (for C.)
-Up to 30 days post last vaccination (for D. and E.)

Main Objective: The study will be randomised into two groups based on the vaccination schedule in relation to the start of a chemotherapy cycle:
- The OnChemo group receives their first HZ/su vaccination at the start of a chemotherapy cycle
- The PreChemo group receives their first HZ/su vaccination at least 10 days before the start of a chemotherapy cycle

•To evaluate anti-gE humoral immune responses at Month 2 (M2), following a two-dose administration of the HZ/su vaccine (post-dose 2), as compared to placebo, in subjects with solid tumours receiving chemotherapy (PreChemo groups only)
•To evaluate the safety and reactogenicity following administration of the HZ/su vaccine as compared to placebo up to 30 days post last vaccination in subjects with solid tumours receiving chemotherapy

Primary end point(s): A. Anti-gE humoral immunogenicity with respect to components of the study/investigational vaccine.in terms of antibody (Ab) concentrations.
-Anti-gE Ab concentrations as determined by ELISA.
B. Occurrence of solicited local and general symptoms.
-Occurrence, intensity and duration of each solicited local symptom.
-Occurrence, intensity, duration and relationship to vaccination of each solicited general symptom.
C. 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.
D. Occurrence of Serious Adverse Events (SAEs).
-Occurrence and relationship to vaccination of SAEs.
E. Occurrence of AEs of specific interest.
-Occurrence and relationship to vaccination of any potential Immune Mediated Diseases (pIMDs).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: -At Month 0, Month 1, Month 6 (Visit 4, at the start of the last cycle of chemotherapy between months 4 and 13) and Month 13 (for A)
-During the period starting after 30 days post last vaccination until study end (Month 13) (for B and C)

Secondary end point(s): A. For immunogenicity with respect to components of the study/investigational vaccine
-Anti-gE Ab concentrations as determined by ELISA at Month 0, Month 1, Month2, Month 6 (Visit 4, at the start of the last cycle of chemotherapy between months 4 and 13) and Month 13
-Vaccine response for anti-gE Abs at Month 1, Month 2, Month 6 (Visit 4, at the start of the last cycle of chemotherapy between months 4 and 13) and Month 13
-Frequencies of gE-specific CD4+ T-cells, expressing at least 2 activation markers (from among IFN-?, IL-2, TNF-a and CD40 L), as determined by in vitro intracellular cytokine staining (ICS), at Month 0, Month 1, Month 2, and Month 13
-Vaccine response for gE-specific CD4+ T-cells expressing at least 2 activation markers (from among IFN-?, IL-2, TNF-a and CD40L), as determined by in vitro ICS, at Month 1, Month 2 and Month 13
B. Occurrence of Serious Adverse Events (SAEs)
-Occurrence and relationship to vaccination of SAEs during the period starting after 30 days post last vaccination until study end
C. Occurrence of AEs of specific interest
-Occurrence of any pIMDs during the period starting after 30 days post last vaccination until study end

Secondary ID(s)

116427

2012-002966-11-ES

Source(s) of Monetary Support

GlaxoSmithKline Biologicals

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 02/07/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002966-11/results