Back to resultsEvaluation of the Long-term Persistence of GlaxoSmithKline (GSK) Biologicals' Candidate Cytomegalovirus (CMV) Vaccine
Primary Purpose
Infections, Cytomegalovirus
Status
Completed
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Blood sampling
GSK149203A
Sponsored by
About this trial
This is an interventional prevention trial for Infections, Cytomegalovirus focused on measuring Cytomegalovirus, Vaccine
Eligibility Criteria
Inclusion Criteria:
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol (e.g., return for follow-up visits) should be enrolled in the study.
- Written informed consent obtained from the subject.
- Healthy subjects as established by clinical evaluation (medical history and physical examination) before entering in the study.
Subjects of the vaccine group should in addition satisfy the following criterion:
• Subjects who participated in the primary study 108890 (NCT00435396), having received 3 doses of the GSK's CMV candidate vaccine and having completed the Year 2 follow-up study 109211 (NCT00435396).
Subjects of the seropositive reference group should in addition satisfy the following criterion:
• Subjects who participated in the screening visit of the primary study 108890 (NCT00435396), and whose blood sample taken at this visit was tested CMV positive.
Exclusion Criteria:
- Use, or planned use, of any investigational or non-registered product (drug or vaccine) during the study period.
- Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to study visit(s). For corticosteroids, this will mean prednisone, 20mg/day, or equivalent. Inhaled and topical steroids are allowed.
- Administration of immunoglobulins and/or any blood products within three months preceding study visit(s).
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
For subjects in the vaccine group, the following exclusion criterion should be checked in addition:
• Administration of any additional CMV vaccine since end of primary study 108890 (NCT00435396).
For subjects in the seropositive reference group, the following exclusion criterion should be checked in addition:
• Administration of any CMV vaccine since the screening visit of primary study 108890 (NCT00435396).
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
GSK149203A S- Group
GSK149203A S+ Group
Arm Description
Male subjects who received 3 doses of GSK Biologicals' candidate GSK149203A vaccine according to a 0-1-6 month schedule in the primary study 108890 (NCT00435396).
Male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
Outcomes
Primary Outcome Measures
Concentrations of Antibodies Against Anti-Glycoprotein B (gB) Immunoglobulin G (IgG)
Anti-gB IgG antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL), as assessed by Enzyme-linked Immunosorbent Assay (ELISA). Data were collected at Month 48 (M48) and Month 60 (M60) from all subjects.
Number of Subjects With Neutralizing Response Against Anti-Cytomegalovirus (CMV) Antibodies
The neutralizing antibodies were to be measured using an in-house micro-neutralization assay.
Secondary Outcome Measures
Descriptive Statistics on Avidity Index (%) of Anti-gB IgG Antibodies
Avidity for anti-gB IgG antibodies was assessed by the ELISA Avidity index method in all subjects, at Month 48 (M48) and Month 60 (M60).
This assay has been developed according to Souza et al (Rev.Inst.med.Trop.S.Paulo 45;323-326; 2003) using an elution step with urea to remove low-avidity antibodies from CMV antigen. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes are exposed to urea divided by the mean absorbance of reactions in which the immune complexes are not exposed to urea, expressed as a percentage.
Descriptive Statistics on the Frequency of gB-specific Cluster of Differentiation (CD4+/CD8+) T-cells Expressing at Least Two Immune Markers
Among the immune markers determined by the Intracellular cytokine staining (ICS) were Interferon-gamma (INF-γ), Interleukin-2 (IL-2), Tumor necrosis factor-alpha (TNF-α), and CD40-Ligand (CD40-L). Data were collected for all subjects at Month 48 (M48) and Month 60 (M60).
Desciptive Statistics on the Frequency of gB-specific Memory B-cells (by ELISPOT)
Memory B cells specific to the CMV gB antigen, as assessed by the Enzyme-linked Immunosorbent Spot (ELISPOT) method, were expressed as a frequency of the specific memory B-cells per million memory B-cells. Data were collected for all subjects at Month 48 (M48) and Month 60 (M60).
Number of Subjects With Response for Anti-CMV Tegument IgG Antibodies
CMV infection was determined by the anti-CMV proteins antibody response, using ELISA. Data were collected for all subjects at Month 48 (M48) and Month 60 (M60) in the Vaccine group (GSK149203A S- Group). All subjects from the Reference group (GSK149203A S+ Group) were positive for the anti-CMV tegument IgG antibodies at the screening visit.
Assessment of CMV Infection by CMV Specific Desoxyribonucleic Acid (DNA) in Viral Load
CMV DNA viral loads were assessed using quantitative Polymerase Chain Reaction (qPCR). Data were presented for subjects included in the Vaccine group (GSK149203A S- Group).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01357915
Brief Title
Evaluation of the Long-term Persistence of GlaxoSmithKline (GSK) Biologicals' Candidate Cytomegalovirus (CMV) Vaccine
Official Title
A Follow-up Study to Evaluate the Long-term Persistence of GSK Biologicals' Candidate CMV Vaccine Administered to Male Adults
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
June 24, 2011 (Actual)
Primary Completion Date
September 13, 2012 (Actual)
Study Completion Date
September 13, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to evaluate the persistence of the vaccine induced immune responses at Month 48 (Year 4) and Month 60 (Year 5) in healthy subjects who received 3 doses of GSK Biologicals' candidate CMV vaccine according to a 0-1-6 month schedule during the primary study 108890 (NCT00435396) (vaccine group). The immune response to CMV infection in naturally infected subjects who participated in the screening visit of the primary study 108890 (NCT00435396) and who were tested CMV-seropositive, will be used as a reference value (seropositive reference group). In addition, this study will continue to assess the occurrence of CMV infections as well as the continued development and validation of read-outs in the CMV project.
The primary vaccination phase and Year 2 follow-up were posted as a separate protocol posting (NCT00435396).
Detailed Description
During the long-term follow-up study, all subjects who received 3 doses of GSK Biologicals' candidate CMV vaccine according to a 0-1-6 month schedule during the primary study 108890 (NCT00435396) will be invited to participate at Visit 8 (Year 4) and Visit 9 (Year 5) as the vaccine group. In addition, the healthy subjects who participated in the screening visit of the primary study 108890 (NCT00435396) and who were tested CMV-seropositive will be invited to Visit 9 (Year 5) of this study as the seropositive reference group.This Protocol Posting has been updated following Protocol Amendment 1, March 2012, leading to the update of brief summary, intervention model, enrolment, outcome measures, eligibility and arms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infections, Cytomegalovirus
Keywords
Cytomegalovirus, Vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSK149203A S- Group
Arm Type
Experimental
Arm Description
Male subjects who received 3 doses of GSK Biologicals' candidate GSK149203A vaccine according to a 0-1-6 month schedule in the primary study 108890 (NCT00435396).
Arm Title
GSK149203A S+ Group
Arm Type
Other
Arm Description
Male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
Intervention Type
Procedure
Intervention Name(s)
Blood sampling
Intervention Description
Blood samples will be collected at 2 time points:
At the long-term follow-up at approximately Month 48 of study (= ± 42 months post dose 3) from all subjects in the vaccine group.
At the long-term follow-up at approximately Month 60 of study (= ± 54 months post dose 3) from all subjects.
Intervention Type
Biological
Intervention Name(s)
GSK149203A
Intervention Description
GSK Biologicals' Recombinant CMV glycoprotein B Vaccine, Intramuscular injection, 3 doses
Primary Outcome Measure Information:
Title
Concentrations of Antibodies Against Anti-Glycoprotein B (gB) Immunoglobulin G (IgG)
Description
Anti-gB IgG antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL), as assessed by Enzyme-linked Immunosorbent Assay (ELISA). Data were collected at Month 48 (M48) and Month 60 (M60) from all subjects.
Time Frame
At Month 48 and Month 60
Title
Number of Subjects With Neutralizing Response Against Anti-Cytomegalovirus (CMV) Antibodies
Description
The neutralizing antibodies were to be measured using an in-house micro-neutralization assay.
Time Frame
At Month 48 and Month 60
Secondary Outcome Measure Information:
Title
Descriptive Statistics on Avidity Index (%) of Anti-gB IgG Antibodies
Description
Avidity for anti-gB IgG antibodies was assessed by the ELISA Avidity index method in all subjects, at Month 48 (M48) and Month 60 (M60).
This assay has been developed according to Souza et al (Rev.Inst.med.Trop.S.Paulo 45;323-326; 2003) using an elution step with urea to remove low-avidity antibodies from CMV antigen. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes are exposed to urea divided by the mean absorbance of reactions in which the immune complexes are not exposed to urea, expressed as a percentage.
Time Frame
At Month 48 and Month 60
Title
Descriptive Statistics on the Frequency of gB-specific Cluster of Differentiation (CD4+/CD8+) T-cells Expressing at Least Two Immune Markers
Description
Among the immune markers determined by the Intracellular cytokine staining (ICS) were Interferon-gamma (INF-γ), Interleukin-2 (IL-2), Tumor necrosis factor-alpha (TNF-α), and CD40-Ligand (CD40-L). Data were collected for all subjects at Month 48 (M48) and Month 60 (M60).
Time Frame
At Month 48 and Month 60
Title
Desciptive Statistics on the Frequency of gB-specific Memory B-cells (by ELISPOT)
Description
Memory B cells specific to the CMV gB antigen, as assessed by the Enzyme-linked Immunosorbent Spot (ELISPOT) method, were expressed as a frequency of the specific memory B-cells per million memory B-cells. Data were collected for all subjects at Month 48 (M48) and Month 60 (M60).
Time Frame
At Month 48 and Month 60
Title
Number of Subjects With Response for Anti-CMV Tegument IgG Antibodies
Description
CMV infection was determined by the anti-CMV proteins antibody response, using ELISA. Data were collected for all subjects at Month 48 (M48) and Month 60 (M60) in the Vaccine group (GSK149203A S- Group). All subjects from the Reference group (GSK149203A S+ Group) were positive for the anti-CMV tegument IgG antibodies at the screening visit.
Time Frame
At Month 48 and Month 60
Title
Assessment of CMV Infection by CMV Specific Desoxyribonucleic Acid (DNA) in Viral Load
Description
CMV DNA viral loads were assessed using quantitative Polymerase Chain Reaction (qPCR). Data were presented for subjects included in the Vaccine group (GSK149203A S- Group).
Time Frame
At Month 48 and Month 60
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects who the investigator believes that they can and will comply with the requirements of the protocol (e.g., return for follow-up visits) should be enrolled in the study.
Written informed consent obtained from the subject.
Healthy subjects as established by clinical evaluation (medical history and physical examination) before entering in the study.
Subjects of the vaccine group should in addition satisfy the following criterion:
• Subjects who participated in the primary study 108890 (NCT00435396), having received 3 doses of the GSK's CMV candidate vaccine and having completed the Year 2 follow-up study 109211 (NCT00435396).
Subjects of the seropositive reference group should in addition satisfy the following criterion:
• Subjects who participated in the screening visit of the primary study 108890 (NCT00435396), and whose blood sample taken at this visit was tested CMV positive.
Exclusion Criteria:
Use, or planned use, of any investigational or non-registered product (drug or vaccine) during the study period.
Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to study visit(s). For corticosteroids, this will mean prednisone, 20mg/day, or equivalent. Inhaled and topical steroids are allowed.
Administration of immunoglobulins and/or any blood products within three months preceding study visit(s).
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
For subjects in the vaccine group, the following exclusion criterion should be checked in addition:
• Administration of any additional CMV vaccine since end of primary study 108890 (NCT00435396).
For subjects in the seropositive reference group, the following exclusion criterion should be checked in addition:
• Administration of any CMV vaccine since the screening visit of primary study 108890 (NCT00435396).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
La Louvière
ZIP/Postal Code
7100
Country
Belgium
Facility Name
GSK Investigational Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
12. IPD Sharing Statement
Learn more about this trial
Evaluation of the Long-term Persistence of GlaxoSmithKline (GSK) Biologicals' Candidate Cytomegalovirus (CMV) Vaccine
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