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Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster (HZ/su) Vaccine in Adults With Solid Tumours Receiving Chemotherapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01798056
First received: February 14, 2013
Last updated: October 5, 2016
Last verified: July 2016
  Purpose
The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' HZ/su vaccine in adults with solid tumours undergoing chemotherapy.

Condition Intervention Phase
Herpes Zoster
Biological: GSK 1437173A
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: An Observer-blind Study to Evaluate Immunogenicity and Safety of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults 18 Years of Age or Older With Solid Tumours Receiving Chemotherapy

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Adjusted geometric means (GMC) of GSK1437173A over placebo for anti-glycoprotein E (gE) antibody enzyme-linked immunosorbent assay (ELISA) concentrations in PreChemo Groups only [ Time Frame: At Month 2 ] [ Designated as safety issue: No ]
  • GMCs for anti-Varicella Zoster Virus (VZV) gE antibodies [ Time Frame: At Month 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of subjects with anti-gE antibody concentrations as determined by ELISA above the cut-off value (97 mIU/mL) [ Time Frame: At Month 2 ] [ Designated as safety issue: No ]
  • Number of subjects with vaccine responses for anti-gE antibody ELISA concentrations [ Time Frame: At Months 1 and 2 ] [ Designated as safety issue: No ]
    Vaccine response defined as: For initially seronegative subjects, antibody concentration at post-vaccination ≥ 4 fold the cut-off for Anti-gE (4x97 mIU/ml); For initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration.

  • Descriptive statistics of the frequency of gE-specific CD4[2+] T-cells [ Time Frame: At Months 0, 1 and 2 ] [ Designated as safety issue: No ]
    Descriptive statistics were tabulated for CD4[2+] cells, which are gE-specific CD4+ T-cells with at least 2 activation markers ([2+]) expressed from the activation markers IFN-γ, IL-2, TNF-α and CD40 L, as determined by intra-cellular staining (ICS) method.

  • Number of subjects with vaccine responses for gE-specific CD4[2+] T-cells [ Time Frame: At Months 1 and 2 ] [ Designated as safety issue: No ]
    Vaccine response defined as: For initially subjects with pre-vaccination T cell frequencies below the threshold, at least a 2-fold increase as compared to the threshold (2x320 Events/10E6 CD4+ T cells); For initially subjects with pre-vaccination T cell frequencies above the threshold, at least a 2-fold increase as compared to pre-vaccination T cell frequencies.

  • Number of subjects with unsolicited adverse events (AEs) [ Time Frame: During the 30-day (Days 0-29) post-vaccination period ] [ Designated as safety issue: No ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  • Number of subjects with serious adverse events (SAEs) [ Time Frame: From the first dose up to 30 days post last vaccination period ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  • Number of subjects with potential Immune Mediated Diseases (pIMDs) [ Time Frame: From first vaccination up to 30 days post last vaccination ] [ Designated as safety issue: No ]

Enrollment: 237
Study Start Date: March 2013
Study Completion Date: May 2016
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HZ/su-PreChemo
Subjects will receive the first dose of GSK 1437173A at least 10 days (up to 1 month) before start of chemotherapy cycle. The second dose of GSK 1437173A vaccine will be administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy.
Biological: GSK 1437173A
2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.
Other Names:
  • HZ/su
  • GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine
Experimental: HZ/su-OnChemo
Subjects will receive the first dose of GSK 1437173A vaccine at the first day (allowing a window of +/- 1 day) of the first (or second) chemotherapy cycle. The second dose of GSK 1437173A vaccine will be administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy.
Biological: GSK 1437173A
2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.
Other Names:
  • HZ/su
  • GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine
Placebo Comparator: Placebo-PreChemo
Subjects will receive the first dose of placebo at least 10 days (up to 1 month) before start of chemotherapy cycle. The second dose of placebo will be administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy.
Drug: Placebo
2 doses administered by IM injection into the deltoid muscle of the non-dominant arm.
Placebo Comparator: Placebo-OnChemo
Subjects will receive the first dose of placebo at the first day (allowing a window of +/- 1 day) of the first (or second) chemotherapy cycle. The second dose of placebo will be administered between 1 and 2 months after the first vaccination and at the first day (allowing a window of +/- 1 day) of a subsequent cycle of chemotherapy.
Drug: Placebo
2 doses administered by IM injection into the deltoid muscle of the non-dominant arm.

Detailed Description:

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.

The protocol summary has been updated following Protocol Amendment 2, August 2014, leading to the increase of the enrolment.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01798056

Locations
Canada, British Columbia
GSK Investigational Site
Kelowna, British Columbia, Canada, V1Y 5L3
Canada, Nova Scotia
GSK Investigational Site
Halifax, Nova Scotia, Canada, B3K 6R8
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M4C 3E7
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H4J 1C5
Czech Republic
GSK Investigational Site
Praha 8, Czech Republic, 180 00
France
GSK Investigational Site
Besançon cedex, France, 25030
GSK Investigational Site
Ferolles-Attilly, France, 77150
GSK Investigational Site
Lyon Cedex 08, France, 69373
GSK Investigational Site
Montpellier, France, 34070
GSK Investigational Site
Nîmes cedex 9, France, 30029
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 02841
GSK Investigational Site
Seoul, Korea, Republic of, 03080
GSK Investigational Site
Seoul, Korea, Republic of, 05505
Spain
GSK Investigational Site
Badajoz, Spain, 6080
GSK Investigational Site
Barcelona, Spain, 08035
GSK Investigational Site
Madrid, Spain, 28007
GSK Investigational Site
Madrid, Spain, 28034
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Madrid, Spain, 28041
GSK Investigational Site
Madrid, Spain, 28050
GSK Investigational Site
Majadahonda (Madrid), Spain, 28222
GSK Investigational Site
Móstoles, Spain, 28935
GSK Investigational Site
Pozuelo de Alarcón/Madrid, Spain, 28223
GSK Investigational Site
San Sebastian de los Reyes, Spain, 28702
United Kingdom
GSK Investigational Site
Cheltenham, Gloucestershire, United Kingdom, GL53 7AN
GSK Investigational Site
Woolwich, London, United Kingdom, SE18 4QH
GSK Investigational Site
Swindon, Wiltshire, United Kingdom, SN3 6BB
GSK Investigational Site
Exeter, United Kingdom, EX2 5DW
GSK Investigational Site
Sheffield, United Kingdom, S10 2SJ
GSK Investigational Site
York, United Kingdom, YO31 8HE
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01798056     History of Changes
Other Study ID Numbers: 116427  2012-002966-11 
Study First Received: February 14, 2013
Last Updated: October 5, 2016
Health Authority: Canada: Health Products and Food Branch of Health Canada
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Korea: Korea Food and Drug Administration (KFDA)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: Statni ustav pro kontrolu leciv

Keywords provided by GlaxoSmithKline:
≥18 years of age
Chemotherapy
Solid tumours
Immunogenicity
Herpes Zoster
Safety
Shingles

Additional relevant MeSH terms:
Herpes Zoster
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 07, 2016