A Study in Adolescent Females to Explore Cytomegalovirus Infection

Study Overview
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Brief Summary
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The purpose of this study is to estimate the incidence of Cytomegalovirus (CMV) secondary infections (re-infections/re-activations) and the incidence of CMV primary infections in adolescent females.

Official Title
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A Study in Adolescent Females to Explore Cytomegalovirus Infection

Conditions
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Infections, Cytomegalovirus

Intervention / Treatment
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* Procedure: Blood collection
* Procedure: Urine collection
* Procedure: Saliva collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A female adolescent between, and including 10 and 17 years at the time of enrolment regardless of pregnancy status and contraception method used or not used. Subjects who the investigator believes that the subject and/or the subject's parent(s)/Legally Acceptable Representative(s) (LAR[s]) can and will comply with the requirements of the protocol. Written informed assent and/or consent obtained from the subject and/or the parent(s)/LAR(s) of the subject. Subject is likely to remain in the area and/or return for required study Site Visits and complete Sample Collection Visits. Exclusion Criteria: Child in care. Use or planned use of any investigational or non-registered antiviral drug or vaccine during the study period. Known medical history of any recurrent clinical herpes episodes requiring episodic or chronic suppressive treatment with oral or parenteral antiviral treatment such as acyclovir, famciclovir, valacyclovir or any other anti-herpes virus anti-viral during the year preceding enrolment. Topical anti-viral are allowed. Subjects with history of previous vaccination against CMV. Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to Visit 1 or planned administration during the study. Inhaled and topical steroids are allowed. Administration of immunoglobulins and/or any blood products within 3 months prior to Visit 1 or planned administration during the study. Any confirmed or suspected immunosuppressive or immunodeficient condition including HIV-infection, based on medical history and physical examination (no laboratory testing required). Any major congenital defects, serious chronic illness or organ transplantation.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group S+<br>Cytomegalovirus (CMV) seropositive subjects aged between 10-17 years at enrollment in the study. | Procedure: Blood collection<br>* Samples collected at Months 0, 4, 8, 12, 16, 20, 24, 28, 32, and 36.<br>Procedure: Urine collection<br>* Samples collected at Months 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36.<br>Procedure: Saliva collection<br>* Samples collected at Months 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36.<br>|
| Experimental: Group S-<br>Cytomegalovirus (CMV) seronegative subjects aged between 10-17 years at enrollment in the study. | Procedure: Blood collection<br>* Samples collected at Months 0, 4, 8, 12, 16, 20, 24, 28, 32, and 36.<br>Procedure: Urine collection<br>* Samples collected at Months 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36.<br>Procedure: Saliva collection<br>* Samples collected at Months 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36.<br>|
| Experimental: Missing serostatus Group<br>Subjects with no confirmed serostatus, aged between 10-17 years at enrollment in the study. | Procedure: Blood collection<br>* Samples collected at Months 0, 4, 8, 12, 16, 20, 24, 28, 32, and 36.<br>Procedure: Urine collection<br>* Samples collected at Months 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36.<br>Procedure: Saliva collection<br>* Samples collected at Months 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV Immunoglobulin G (IgG) concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 4 | 
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV IgG concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 8 | 
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV IgG concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 12 | 
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV IgG concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 16 | 
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV IgG concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 20 | 
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV IgG concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 24 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point). | At Month 8 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point). | At Month 12 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point). | At Month 16 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point). | At Month 20 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point). | At Month 24 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point) | At Month 28 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point). | At Month 32 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point). | At Month 36 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV Deoxyribonucleic Acid (DNA) Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR), for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL) and for CMV seropositive subjects with increase of CMV DNA (≥6720 copies/mL) and 0<DNA copies <LLOQ (6720 copies/mL) in prior urine sample (category name= ≥6720 copies/mL). | At Month 4 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV DNA Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR),for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL) and for CMV seropositive subjects with increase of CMV DNA (≥6720 copies/mL) and 0<DNA copies <LLOQ (6720 copies/mL) in prior urine sample (category name= ≥6720 copies/mL). | At Month 8 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV DNA Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR),for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL). | At Month 12 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV DNA Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR),for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL). | At Month 16 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV DNA Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR),for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL). | At Month 20 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV DNA Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR),for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL). | At Month 24 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV DNA Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR),for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL) and for CMV seropositive subjects with increase of CMV DNA (≥6720 copies/mL) and 0<DNA copies <LLOQ (6720 copies/mL) in prior urine sample (category name= ≥6720 copies/mL). | At Month 28 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV DNA Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR),for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL). | At Month 32 | 
| Geometric Mean CMVpp65 Antibody Concentration in Subjects Based on Number of CMV DNA Copies (pp65 Gene) in Urine | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. The concentration of DNA copies was assessed by quantitative Polymerase Chain Reaction (qPCR),for CMV seropositive subjects with appearance of CMV DNA (>0 copies/mL) and DNA copies=0 in prior urine sample (category=> 0 Copies/mL). | At Month 36 | 
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV IgG concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 28 | 
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV IgG concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 32 | 
| Number of CMV Seropositive Subjects With Appearance or Increase of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. Two-fold and above increases category = subjects that had two-fold and above increases of anti-CMV IgG concentration. Four-fold and above increases = subjects that had four-fold and above increases of anti-CMV IgG concentration. The cut-off of the assay = 1.136 ELISA unit (EU)/mL. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. | At Month 36 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. | At Month 0 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration in Serum (ELISA). | This outcome was part of the assessment of occurrence of CMV secondary infections determined in all seropositive subjects. A seropositive subject is a subject for whom anti-CMV IgG antibodies were detected in serum sample collected at Month 0. CMV secondary infections are defined as either a viral reactivation or a re-infection with a new strain of CMV. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. GMC was calculated on subjects meeting a two-fold increase or above (i.e.: subjects that had two-fold and above increases [including four-fold] of CMV anti-tegument IgG compared with previous time point). | At Month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of CMV Seronegative Subjects With Appearance of Anti-CMV Tegument Protein IgG Antibodies in Serum. | This outcome was part of the assessment of occurrence of CMV primary infections determined in all seronegative subjects, on samples collected during the 4-month site visits until study conclusion. A seronegative subject is a subject for whom anti-CMV IgG antibodies were not detected in serum sample collected at Month 0. CMV primary infection is defined as the first infection with CMV in subjects who were seronegative at enrollment. | From study Month 0 to Month 36 | 
| Anti-CMV Tegument Protein IgG Antibody Concentration of Seronegative Subjects | This outcome is part of the assessment of occurrence of CMV primary infections determined in all seronegative subjects, on samples collected during the 4-month site visits until study conclusion. A seronegatve subject is a subject for whom anti-CMV IgG antibodies were not detected in serum sample collected at Month 0. CMV primary infection is defined as the first infection with CMV in subjects who were seronegative at enrollment. Antibody concentrations were tabulated as geometric mean concentrations (GMC) and expressed as ELISA units (EU)/mL. The cut-off of the assay = 1.136 EU/mL. | From study Month 0 to Month 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescent females, Cytomegalovirus (CMV)