Study of the Transmission of Cytomegalovirus (CMV) Infection From Mother to Foetus

Cytomegalovirus Infections Clinical Trial

Official title:

Study of Maternal-foetal Cytomegalovirus (CMV) Transmission

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01251744
• Other study ID #: 113134
• Status: Completed
• Phase: N/A
• Start date: December 9, 2010
• Est. completion date: June 17, 2015

Study information

• Verified date: May 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate maternal virological and immunological parameters to determine their ability to predict congenital cytomegalovirus (CMV) infection. When a pregnant woman is infected with CMV, her immune system (which protects her from infection) is activated and the virus can be found in the woman's bodily fluids (blood, saliva, urine, vaginal secretions). The aim of this study is to find out if there is a link between either the pregnant woman's immune response or the presence of the virus in these bodily fluids and the child/foetus being infected with the virus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: June 17, 2015
• Est. primary completion date: November 6, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol .

• A pregnant female, 18 years of age or older at the time of study enrolment.

• Women with confirmed primary CMV infection.

• Written informed consent obtained from the subject.

Exclusion Criteria:

• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to study entry.

• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational pharmaceutical product.

• Previous vaccination against CMV infection.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history or physical examination

• Major congenital defects, serious chronic illness or organ transplantation.

• Administration of immunoglobulins and/or any blood products within the three months preceding study enrolment or during the pregnancy.

• Documented Human immunodeficiency virus (HIV)-positive subject.

• Gestational age of more than 34 weeks, as determined by foetal ultrasound.

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• Infection
• Infections, Cytomegalovirus

Intervention

Procedure:
• Blood sample
Blood sample at study entry, every two months during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion.
• Cord blood sample
Cord blood sample taken at the time of delivery.
• Saliva swab
Saliva swab taken at study entry, every month during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion.
• Urine sampling
Approximately 10 mL of urine will be sampled at study entry, every month during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion.
• Vaginal swab
Vaginal swab taken at study entry, every month during pregnancy and one month after pregnancy conclusion.

Locations

Country	Name	City	State
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Charleroi
Belgium	GSK Investigational Site	La Louvière
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Liège
Belgium	GSK Investigational Site	Mons
Belgium	GSK Investigational Site	Wilrijk

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Any Cytomegalovirus (CMV) Congenital Infection	The CMV congenital infections were assessed in newborns and foetuses of subjects who had a confirmed primary CMV infection during pregnancy.	At Month 0
Primary	Number of Subjects With CMV Presence in the Urine	Evidence of infection in urine was assessed by culture or by Polymerase Chain Reaction (PCR).	Within 10 days post-delivery (Days 0-9)
Primary	Number of Subjects With CMV Presence in the Amniotic Fluid	Evidence of infection in the amniotic fluid was assessed by culture or by Polymerase Chain Reaction (PCR).	Within 10 days post-delivery (Days 0-9)
Primary	Evidence of CMV DNA or CMV Inclusions in Tissues of an Aborted or Stillborn Foetus		Within 10 days post-delivery (Days 0-9)
Primary	Number of CMV DNA Copies in Saliva, Urine, Blood or Vaginal Secretions	The assessment focused on the presence of CMV DNA copies (by Quantitative Polymerase Chain Reaction [qPCR]) in saliva, urine, blood and vaginal secretions every month from study entry to, and including, pregnancy conclusion.	At Month 0
Primary	Number of CMV DNA Copies in Saliva, in Urine and in Blood or Vaginal Secretions	The assessment focused on the presence of CMV DNA copies (by Quantitative Polymerase Chain Reaction [qPCR]) in saliva, urine and blood every month from study entry to, and including, pregnancy conclusion.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	Descriptive Statistics of the Anti-CMV Immunoglobulin Type M (IgM) Status	Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.	At Month 0
Primary	Descriptive Statistics of the Anti-CMV IgM Status	Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.	At Month 2
Primary	Descriptive Statistics of the Anti-Cytomegalovirus (Anti-CMV) Immunoglobulin Type M (IgM) Status	Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.	At Month 4
Primary	Anti-CMV Immunoglobulin Type M (IgM) Status, Descriptive Statistics	Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects.	At Month 6
Primary	Descriptive Statistics for the Anti-CMV IgM Status	Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	Anti-glycoprotein B (gB) Immunoglobulin Type G (IgG) Antibody Concentrations	Anti-gB IgG concentrations were assessed by ELISA, presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EU/mL). The cut-off value was greater than or equal to (=) 54 EU/mL.	At Month 0
Primary	Anti-gB IgG Antibody Concentrations	Anti-gB IgG concentrations were assessed by ELISA, presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EU/mL). The cut-off value was greater than or equal to (=) 54 EU/mL.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	Descriptive Statistics of the Anti-glycoprotein B (gB) Immunoglobulin Type G (IgG) Avidity Index	The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.	At Month 0
Primary	Descriptive Statistics of the Anti-gB IgG Avidity Index	The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	CMV-specific Cluster of Differentiation 4 (CD4) T-cell Frequencies	Descriptive statistics of the frequency of CMV-specific CD4 T cells expressing at least two markers among: cluster of differentiation 40 ligand (CD40L), interleukin-2 (IL-2), interferon-gamma (IFN-?), tumor necrosis factor-alpha (TNF-a), as assessed by Intracellular Cytokine Staining [ICS], by stimulating agent (among Human Cytomegalovirus [HCMV] immediate-early gene [IE1] antigen, HCMV glicoprotein B [gB] antigen, HCMV lysate antigen and HCMV pp65 antigen).	At Month 0
Primary	CMV-specific CD4 T-cell Frequencies	Descriptive statistics of the frequency of CMV-specific CD4 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining [ICS], by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	CMV-specific Cluster of Differentiation 8 (CD8) T-cell Frequencies	Descriptive statistics of the frequency of CMV-specific CD8 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining [ICS], by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).	At Month 0
Primary	CMV-specific CD8 T-cell Frequencies	Descriptive statistics of the frequency of CMV-specific CD8 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining [ICS], by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	CMV-specific Proliferating Cluster of Differentiation (CD4) T Cells Frequencies	Labelled cells were quantified by flow cytometry, by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).	At Month 0
Primary	CMV-specific Proliferating CD4 T Cells Frequencies	Labelled cells were quantified by flow cytometry, by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).; Note: Results were retrieved by subtracting the background without imputing the negative and zero values, this generated negative values.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	Concentrations of Anti-CMV Tegument Protein Immunoglobulin G (IgG) Antibodies	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (=) 0.668 U/mL.	At Day 0 = study entry
Primary	Anti-CMV Tegument Protein Immunoglobulin G (IgG) Antibody Concentrations	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (=) 0.668 U/mL.	At Month 2
Primary	Concentrations of Anti-CMV Tegument Protein IgG Antibodies	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (=) 0.668 U/mL.	At Month 4
Primary	Anti-CMV Tegument Protein IgG Antibody Concentrations	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (=) 0.668 U/mL.	At Month 6
Primary	Concentrations of Anti-CMV IgG Antibodies	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (=) 0.668 U/mL.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	Descriptive Statistics of the Anti-CMV Tegument Protein Globulin Type B (gB) Immunoglobulin G (IgG) Avidity, by Congenital Infection Status	Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.	At Day 0 = study entry
Primary	Descriptive Statistics of the Anti-CMV Tegument Protein gB Immunoglobulin G (IgG) Avidity, by Congenital Infection Status	Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.	At Month 2
Primary	Descriptive Statistics of the Anti-CMV Tegument Protein gB IgG Avidity, by Congenital Infection Status	Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.	At Month 4
Primary	Descriptive Statistics of the Anti-CMV Tegument Protein Globulin Type B (gB) IgG Avidity, by Congenital Infection Status	Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.	At Month 6
Primary	Anti-CMV Tegument Protein Globulin Type B (gB) Immunoglobulin G (IgG) Avidity Descriptive Statistics, by Congenital Infection Status	Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 10 ED50.	At Month 0
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 10 ED50.	At Month 2
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 10 ED50.	At Month 4
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 10 ED50.	At Month 6
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 10 ED50.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 15 ED50.	At Month 0
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 15 ED50.	At Month 2
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 15 ED50.	At Month 4
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 15 ED50.	At Month 6
Primary	Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)	Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of = 10 ED50.	At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)