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Study to Assess the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine in Adults Aged 18 Years and Older With Blood Cancers

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01767467
First Posted: January 14, 2013
Last Update Posted: May 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
The purpose of this study is to evaluate the safety and immunogenicity of GSK Biologicals' vaccine GSK1437173A in subjects aged 18 years and older with blood cancers. The study will evaluate safety-related events and antibody and cellular immune responses to the study vaccine, as compared to placebo.

Condition Intervention Phase
Herpes Zoster Biological: Herpes zoster vaccine (GSK 1437173A) Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Study to Evaluate Safety and Immunogenicity of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults Aged 18 Years and Older With Haematologic Malignancies

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Vaccine Response Rates (VRR) for Anti-gE Antibody ELISA Concentrations [ Time Frame: At Month 2 ]

    Vaccine response rate was the number of subjects with a vaccine response. Vaccine response was defined as:

    For initially seronegative subjects, antibody concentration at Month 2 ≥ 4 fold the cut-off for Anti-gE (4x97 mIU/mL) For initially seropositive subjects, antibody concentration at Month 2 ≥ 4 fold the pre-vaccination antibody concentration This analysis was performed in subjects with haematologic malignancies excluding subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.


  • Adjusted Geometric Mean Concentration of Anti-gE Antibodies [ Time Frame: At Month 2 ]
    The Adjusted geometric mean concentration was measured in all subjects excluding those with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms. [ Time Frame: Up to 7 days (Days 0-6) after each vaccination ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. Since the study is ongoing, results for the individual groups are blinded. Hence results were presented per the total number of subjects.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: during the 7-day (Days 0-6) post-vaccination period ]
    Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache, myalgia, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). [ Time Frame: Up to 30 days (Days 0-29) after each vaccination ]
    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 first vaccination up to 30 days post last vaccination ]
    Serious adverse events (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 Reporting Any Potential Immune-mediated Diseases (pIMDs) [ Time Frame: Up to 30 days post last vaccination ]
    Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

  • Number of Days With Solicited Local Symptoms [ Time Frame: within 7 days (Days 0-6) after each vaccination ]
  • Number of Days With Solicited General Symptoms [ Time Frame: within the 7 days (Day 0-6) after each vaccination ]

Secondary Outcome Measures:
  • Occurrence of Confirmed HZ Cases [ Time Frame: From Month 0 until study end ]
  • Number of Subjects With Antibody Titer Equal to or Above Cut-off [ Time Frame: At Month 2 ]
    This parameter was assessed in all vaccinated subjects excluding subjects with Non-Hodgkin B-cell Lymphoma. The cut-off value is 97 mIU/mL.

  • Anti-gE Antibody Concentration [ Time Frame: At Month 2 ]
    Concentrations were presente as geometeric mean concentrations (GMCs) and expressed as milli-international units per milliliter (mIU/mL).This parameter was assessed in all vaccinated subjects excluding subjects with Non-Hodgkin B-cell Lymphoma.

  • Concentrations of Anti-gE Antibodies [ Time Frame: At Month 0, Month 1, Month 2 and Month 13 ]

    Antibody concentrations given in enzyme linked immunosorbent assay (ELISA) units per millilitre (EU/mL) were expressed as Geometric Mean Concentrations (GMCs) in all subjects.

    Note: results for Month 13 were not yeat available at the time of this posting.We will update them once they become available.


  • Vaccine Response Rates (VRR) for Anti-gE Antibody ELISA Concentrations [ Time Frame: At Month 1, Month 2 and Month 13 ]
    The vaccine response rate (VRR) was defined as the percentage of subjects who have at least a 4-fold increase in the anti-gE Ab concentration as compared to the pre-vaccination anti-gE Ab concentration, for subjects who are seropositive at baseline or, at least a 4-fold increase in the anti-gE Ab concentration as compared to the anti-gE Ab cut-off value for seropositivity, for subjects who are seronegative at baseline. Vaccine response was measured in all subjects.

  • Frequency of gE -Specific Cluster of Differentiation 4+ T Cells (CD4+) Expressing at Least 2 Activation Markers [ Time Frame: At Month 0, Month 1, Month 2 and Month 13 ]
    Among markers expressed were interferon-gamma (IFN-γ), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 ligand (CD40L), as determined by in vitro intracellular cytokine staining (ICS). Note: results for Month 13 were not yeat available at the time of this posting.We will update them once they become available.

  • Vaccine Response Rates (VRR) for gE-specific CD4 [2+] T-cells, Expressing at Least 2 Activation Markers. [ Time Frame: At Month 1, Month 2 and Month 13 ]

    Among markers expressed were IFN-γ, IL-2, TNF-α and CD40L, as determined by in vitro ICS. 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 (2x<320> Events/106 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


  • Anti-gE Humoral Immunogenicity in Subjects With Confirmed HZ and Matched Controls [ Time Frame: At Month 0 and at Month 2 ]
  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From first vaccination up to 6 months post last vaccination ]
    Serious adverse events (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 Reporting Any Potential Immune-mediated Diseases (pIMDs) [ Time Frame: From first vaccination up to 6 months post last vaccination ]
    Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology


Enrollment: 568
Study Start Date: March 1, 2013
Study Completion Date: January 6, 2017
Primary Completion Date: January 7, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccine Group
Subjects will receive the candidate HZ vaccine (GSK 1437173A).
Biological: Herpes zoster vaccine (GSK 1437173A)
2 doses administered intramuscularly (IM) in deltoid region of non-dominant arm. Dose 1 administered at Day 0. Dose 2 administered 1-2 months post Dose 1.
Placebo Comparator: Placebo Group
Subjects will receive the placebo vaccine.
Drug: Placebo
2 doses administered intramuscularly (IM) in deltoid region of non-dominant arm. Dose 1 administered at Day 0. Dose 2 administered 1-2 months post Dose 1.

Detailed Description:

Amendment to protocol posting:

Increase in sample size, update of country/region-specific information (Sections 5, 6 and 9).

Promotion of secondary to primary objective; related update of primary and secondary outcome measures (Sections 4 and 7).

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

    • Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
  • Female subjects of childbearing potential may be enrolled inthe 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:

  • 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).
  • Human immunodeficiency virus (HIV) infection by clinical history.
  • Use of any investigational or non-registered product 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.
  • 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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01767467


  Show 86 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01767467     History of Changes
Other Study ID Numbers: 116428
2012-003438-18 ( EudraCT Number )
First Submitted: January 10, 2013
First Posted: January 14, 2013
Results First Submitted: January 5, 2017
Results First Posted: May 25, 2017
Last Update Posted: May 25, 2017
Last Verified: March 2017

Keywords provided by GlaxoSmithKline:
Immunogenicity
Safety
Herpes zoster
Vaccination
Haematologic malignancies

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