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

A Follow-up Study to Evaluate the Long-term Persistence of GSK Biologicals' Candidate CMV Vaccine Administered to Male Adults

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01357915

Enrollment

Registered

2011-05-23

Start date

2011-06-24

Completion date

2012-09-13

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Infections, Cytomegalovirus

Keywords

Cytomegalovirus, Vaccine

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.

Interventions

PROCEDUREBlood 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.

BIOLOGICALGSK149203A

GSK Biologicals' Recombinant CMV glycoprotein B Vaccine, Intramuscular injection, 3 doses

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 45 Years

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).

Design outcomes

Primary

Measure	Time frame	Description
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.
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

Measure	Time frame	Description
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).
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.
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).
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.
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).

Countries

Belgium

Participant flow

Recruitment details

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

Participants by arm

Arm	Count
GSK149203A S- Group 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).	30
GSK149203A S+ Group Healthy male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396).	17
Total	47

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	3	0

Baseline characteristics

Characteristic	GSK149203A S- Group	GSK149203A S+ Group	Total
Age, Continuous	34.3 Years STANDARD_DEVIATION 6.37	35.5 Years STANDARD_DEVIATION 7.2	34.73 Years STANDARD_DEVIATION 6.63
Race/Ethnicity, Customized Other: unknown	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized White-Caucasian/European heritage	30 Participants	16 Participants	46 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	30 Participants	17 Participants	47 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 17
other Total, other adverse events	0 / 0	0 / 0
serious Total, serious adverse events	0 / 30	0 / 17

Outcome results

Primary

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.