Evaluation of the Long-term Persistence of GlaxoSmithKline (GSK) Biologicals' Candidate Cytomegalovirus (CMV) Vaccine

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01357915
• Collaborator: (none)
• Enrollment: 47
• Locations: 2
• Arms: 2
• Actual Duration (Months): 14.7
• Patients Per Site: 23.5
• Patients Per Site Per Month: 1.6

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Infections, Cytomegalovirus	Procedure: Blood sampling; Biological: GSK149203A	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Follow-up Study to Evaluate the Long-term Persistence of GSK Biologicals' Candidate CMV Vaccine Administered to Male Adults
• Actual Study Start Date: Jun 24, 2011
• Actual Primary Completion Date: Sep 13, 2012
• Actual Study Completion Date: Sep 13, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK149203A S- Group 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).	Procedure: Blood sampling; 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.; Biological: GSK149203A; GSK Biologicals' Recombinant CMV glycoprotein B Vaccine, Intramuscular injection, 3 doses
Other: GSK149203A S+ Group Male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).	Procedure: Blood sampling; 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.

Outcome Measures

Primary Outcome Measures

1. Concentrations of Antibodies Against Anti-Glycoprotein B (gB) Immunoglobulin G (IgG) [At Month 48 and Month 60]

   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.

2. Number of Subjects With Neutralizing Response Against Anti-Cytomegalovirus (CMV) Antibodies [At Month 48 and Month 60]

   The neutralizing antibodies were to be measured using an in-house micro-neutralization assay.

Secondary Outcome Measures

1. Descriptive Statistics on Avidity Index (%) of Anti-gB IgG Antibodies [At Month 48 and Month 60]

   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.

2. Descriptive Statistics on the Frequency of gB-specific Cluster of Differentiation (CD4+/CD8+) T-cells Expressing at Least Two Immune Markers [At Month 48 and Month 60]

   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).

3. Desciptive Statistics on the Frequency of gB-specific Memory B-cells (by ELISPOT) [At Month 48 and Month 60]

   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).

4. Number of Subjects With Response for Anti-CMV Tegument IgG Antibodies [At Month 48 and Month 60]

   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.

5. Assessment of CMV Infection by CMV Specific Desoxyribonucleic Acid (DNA) in Viral Load [At Month 48 and Month 60]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	La Louvière		Belgium	7100
2	GSK Investigational Site	Wilrijk		Belgium	2610

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01357915
• Other Study ID Numbers: 115429; 2011-002702-78
• First Posted: May 23, 2011
• Last Update Posted: Jan 13, 2020
• Last Verified: Dec 1, 2019

• Keywords provided by GlaxoSmithKline: Cytomegalovirus; Vaccine
• Additional relevant MeSH terms: Cytomegalovirus Infections

Study Results

Participant Flow

Recruitment Details	Subjects from the GSK149203A S+ Group participated only in the Month 60 time point of the study.

Arm/Group Title	GSK149203A S- Group	GSK149203A S+ Group
Arm/Group Description	Healthy 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).	Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
Period Title: Overall Study
STARTED	30	17
COMPLETED	27	17
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	GSK149203A S- Group	GSK149203A S+ Group	Total
Arm/Group Description	Healthy 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).	Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).	Total of all reporting groups
Overall Participants	30	17	47
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.3 (6.37)	35.5 (7.20)	34.73 (6.63)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	30 100%	17 100%	47 100%
Race/Ethnicity, Customized (Number) [Number]
White-Caucasian/European heritage	30 100%	16 94.1%	46 97.9%
Other: unknown	0 0%	1 5.9%	1 2.1%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK149203A S- Group	GSK149203A S+ Group
Arm/Group Description	Healthy 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).	Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
Measure Participants	27	16
Anti-gB IgG, M48	5091.4
Anti-gB IgG, M60	5495.1	2587.2

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The persistence of the functional antibodies for Month 48 and Month 60 could not be analysed, due to the general deterioration of CMV-001/CMV-008 samples.

Arm/Group Title	GSK149203A S- Group	GSK149203A S+ Group
Arm/Group Description	Healthy 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).	Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
Measure Participants	0	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK149203A S- Group	GSK149203A S+ Group
Arm/Group Description	Healthy 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).	Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
Measure Participants	27	16
Anti-gB IgG, M48	74
Anti-gB IgG, M60	68	76

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK149203A S- Group	GSK149203A S+ Group
Arm/Group Description	Healthy 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).	Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
Measure Participants	26	15
CD4-All doubles, M48	2169.00
CD4-All doubles, M60	1893.50	380.00
CD8-All doubles, M48	91.00
CD8-All doubles, M60	104.00	81.00

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK149203A S- Group	GSK149203A S+ Group
Arm/Group Description	Healthy 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).	Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
Measure Participants	27	16
Memory B-cells, M48	3158.00
Memory B-cells, M60	5784.00	210.50

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK149203A S- Group
Arm/Group Description	Healthy 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).
Measure Participants	30
Positive anti-CMV antibodies, M48	0 0%
Negative anti-CMV antibodies, M48	26 86.7%
Missing anti-CMV antibodies, M48	4 13.3%
Positive anti-CMV antibodies, M60	2 6.7%
Negative anti-CMV antibodies, M60	25 83.3%
Missing anti-CMV antibodies, M60	3 10%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK149203A S- Group
Arm/Group Description	Healthy 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).
Measure Participants	30
Count of Participants [Participants]	NA NaN

Adverse Events

Time Frame	Serious Adverse Events (SAEs) and other adverse events: during the entire study period (from Month 48 up to Month 60) there were no SAEs or other significant AEs reported in the study.
Adverse Event Reporting Description	Other (non-serious) Adverse Events were not collected in the study.
Arm/Group Title	GSK149203A S- Group		GSK149203A S+ Group
Arm/Group Description	Healthy 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).		Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).
All Cause Mortality
	GSK149203A S- Group		GSK149203A S+ Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/17 (0%)
Serious Adverse Events
	GSK149203A S- Group		GSK149203A S+ Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	GSK149203A S- Group		GSK149203A S+ Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.