Evaluate Vaccine Against Chickenpox and a Combined Vaccine Against 4 Viral Childhood Diseases: Measles, Mumps, Rubella and Chickenpox

Varicella Clinical Trial

Official title:

Study in Healthy Children (<2 Years) to Evaluate the Safety and Efficacy of GSK Biologicals' Live Attenuated Varicella Vaccine (VarilrixTM) and of GSK Biologicals' Combined Measles-Mumps-Rubella-Varicella Vaccine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00226499
• Other study ID #: 100388
• Secondary ID: 104105 (EXT FU Y
• Status: Completed
• Phase: Phase 3
• Start date: September 1, 2005
• Est. completion date: October 12, 2006

Study information

• Verified date: August 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An observer-blind study to evaluate GlaxoSmithKline Biologicals' live attenuated varicella vaccine and GlaxoSmithKline Biologicals' combined measles-mumps-rubella-varicella vaccine in the prevention of varicella disease in children. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Description:

According to treatment group allocation, participants will receive study vaccines and be followed for antibody titres and occurrence of varicella disease.

This study is conducted in 2 phases. Phase A includes the vaccination period and an observation period for efficacy. The efficacy endpoints will be evaluated over at least two years after vaccination. During this period, the immunogenicity endpoints will be evaluated with respect to the immune response 43 days after vaccination and the persistence of antibodies over two years to varicella (for all subjects) and to measles, mumps and rubella (for a subset of subjects). Regarding the safety endpoints, SAEs (including any complicated varicella cases if observed) will be assessed for all subjects during the whole Phase A duration, whereas, solicited (local and general) and unsolicited adverse events will be assessed in a subset of subjects within a 43-day period after vaccination.

Phase B is an extension of Phase A. It is a long-term follow-up until Year 10 to examine the long-term efficacy of the study vaccines against clinical varicella disease as well as the long-term persistence of antibodies to varicella (for all subjects) and to measles, mumps and rubella (in a subset of subjects) after vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5803
• Est. completion date: October 12, 2006
• Est. primary completion date: October 12, 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 11 Months to 22 Months

Eligibility

Inclusion criteria:

• Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol for the whole duration of the study.

• Male or female subject between 12 and 22 months of age at the time of the first vaccination.

• Subjects free of obvious health problems, as established by medical history and physical examination before entering the study.

• Written informed consent obtained from the parents/guardians of the subject after they have been informed on the risks and benefits of the study, in a language they clearly understand and before performance of any study procedure.

• Subjects whose parents/guardians have direct access to telephone/mobile phone.

• Subjects:

1. with at least one sibling (with negative history of varicella disease/vaccination) at home, or

2. attending day care center, or

3. attending childminders, i.e. someone taking care of several children, or

4. who are in contact for at least once a week with other children without a known positive history of varicella disease/vaccination, while playing in close physical contact for more than 5 minutes.

Exclusion criteria:

• Previous vaccination against measles, mumps, rubella and/or varicella.

• History of previous measles, mumps, rubella and/or varicella/ herpes zoster diseases.

• Known exposure to measles, mumps, rubella and/or varicella/herpes zoster within 30 days prior to the start of the study.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.

• Administration of immunoglobulins and/or any blood products within three months prior to the first vaccine dose or planned administration during the study period.

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

• Family history of congenital or hereditary immunodeficiency.

• History of allergic diseases or reactions likely to be exacerbated by any component of the vaccines, including systemic allergy to egg proteins or neomycin.

• Major congenital defects or serious chronic illness.

• Residence in the same household as newborns (0-4 weeks of age), pregnant women who are varicella-susceptible, persons with a known immunodeficiency or any other persons at high risk for varicella.

• History of any neurologic disorders or seizures.

• Use of any investigational or non-registered product (drug/vaccine other than the study vaccines) within 14 days prior to vaccination and planned use during the study period.

Additional exclusion criteria for subjects included in the subset:

• Administration of a licensed vaccine within 14 days prior to vaccination and planned use until approximately 42 days after the last study vaccine dose (Day 84) with the exception of oral polio vaccine (OPV).

Related Conditions & MeSH terms

• Chickenpox
• Chickenpox Vaccines
• Herpes Zoster
• Rubella
• Varicella

Intervention

Biological:
• Priorix-tetra™
2 doses administered subcutaneously, one at Day 0 and the other at Day 42 to subjects in MMRV Group
• Priorix™
2 doses administered subcutaneously, one at Day 0 and the other at Day 42 to subjects in MMR Group and one dose administered subcutaneously at Day 0 to subjects in OKAH Group
• Varilrix™
1 dose administered subcutaneously at Day 42 to subjects in OKAH Group

Locations

Country	Name	City	State
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Chomutov
Czechia	GSK Investigational Site	Decin
Czechia	GSK Investigational Site	Havlickuv Brod
Czechia	GSK Investigational Site	Hradec Kralove
Czechia	GSK Investigational Site	Humpolec
Czechia	GSK Investigational Site	Jindrichuv Hradec
Czechia	GSK Investigational Site	Kolin
Czechia	GSK Investigational Site	Liberec
Czechia	GSK Investigational Site	Moravska Ostrava
Czechia	GSK Investigational Site	Nachod
Czechia	GSK Investigational Site	Ostrava
Czechia	GSK Investigational Site	Pardubice
Czechia	GSK Investigational Site	Plzen
Czechia	GSK Investigational Site	Praha 4
Czechia	GSK Investigational Site	Praha 4
Czechia	GSK Investigational Site	Praha 5
Czechia	GSK Investigational Site	Praha 6
Czechia	GSK Investigational Site	Praha 9
Czechia	GSK Investigational Site	Znojmo
Greece	GSK Investigational Site	Arta
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Giannitsa
Greece	GSK Investigational Site	Karditsa
Greece	GSK Investigational Site	Komotini
Greece	GSK Investigational Site	Ptolemaida
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Tripolis
Greece	GSK Investigational Site	Veria
Italy	GSK Investigational Site	Alghero (SS)	Sardegna
Italy	GSK Investigational Site	Ferrara	Emilia-Romagna
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Novara	Piemonte
Italy	GSK Investigational Site	Ozieri (SS)	Sardegna
Italy	GSK Investigational Site	Quarto (NA)	Campania
Italy	GSK Investigational Site	Udine	Friuli-Venezia-Giulia
Lithuania	GSK Investigational Site	Alytus
Lithuania	GSK Investigational Site	Kaunas
Lithuania	GSK Investigational Site	Klaipeda
Lithuania	GSK Investigational Site	Panevezys
Lithuania	GSK Investigational Site	Siauliai
Lithuania	GSK Investigational Site	Vilnius
Lithuania	GSK Investigational Site	Vilnius
Lithuania	GSK Investigational Site	Vilnius
Norway	GSK Investigational Site	Bekkestua
Norway	GSK Investigational Site	Moelv
Norway	GSK Investigational Site	Paradis
Norway	GSK Investigational Site	Skien
Norway	GSK Investigational Site	Trondheim
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Debica
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Olesnica
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Siemianowice Slaskie
Poland	GSK Investigational Site	Tarnow
Poland	GSK Investigational Site	Trzebnica
Poland	GSK Investigational Site	Wesola
Poland	GSK Investigational Site	Wroclaw
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Sibiu
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Ivanteevka Moscow Region
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Murmansk
Russian Federation	GSK Investigational Site	Novokuznetsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Samara
Russian Federation	GSK Investigational Site	Sankt-Peterburg
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Volgograd
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Dlha nad Oravou
Slovakia	GSK Investigational Site	Dolny Kubin
Slovakia	GSK Investigational Site	Dubnica Nad Vahom
Slovakia	GSK Investigational Site	Nova Dubnica
Slovakia	GSK Investigational Site	Nove Mesto nad Vahom
Slovakia	GSK Investigational Site	Nove Zamky
Slovakia	GSK Investigational Site	Puchov
Slovakia	GSK Investigational Site	Ruzomberok
Slovakia	GSK Investigational Site	Sturovo
Slovakia	GSK Investigational Site	Surany
Slovakia	GSK Investigational Site	Trencin
Sweden	GSK Investigational Site	Linköping
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Norrköping
Sweden	GSK Investigational Site	Örebro
Sweden	GSK Investigational Site	Umeå

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Czechia,  Greece,  Italy,  Lithuania,  Norway,  Poland,  Romania,  Russian Federation,  Slovakia,  Sweden, 

References & Publications (3)

Carryn S, Feyssaguet M, Povey M, Di Paolo E. Long-term immunogenicity of measles, mumps and rubella-containing vaccines in healthy young children: A 10-year follow-up. Vaccine. 2019 Aug 23;37(36):5323-5331. doi: 10.1016/j.vaccine.2019.07.049. Epub 2019 Jul 22. — View Citation

Henry O, Brzostek J, Czajka H, Leviniene G, Reshetko O, Gasparini R, Pazdiora P, Plesca D, Desole MG, Kevalas R, Gabutti G, Povey M, Innis B. One or two doses of live varicella virus-containing vaccines: Efficacy, persistence of immune responses, and safety six years after administration in healthy children during their second year of life. Vaccine. 2018 Jan 8;36(3):381-387. doi: 10.1016/j.vaccine.2017.11.081. Epub 2017 Dec 7. Erratum in: Vaccine. 2018 Oct 29;36(45):6894. — View Citation

Prymula R, Bergsaker MR, Esposito S, Gothefors L, Man S, Snegova N, Stefkovicova M, Usonis V, Wysocki J, Douha M, Vassilev V, Nicholson O, Innis BL, Willems P. Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial. Lancet. 2014 Apr 12;383(9925):1313-24. doi: 10.1016/S0140-6736(12)61461-5. Epub 2014 Jan 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase A: Number of Subjects With Confirmed Varicella Case	Confirmed varicella case = A case that met the clinical case definition [an illness with acute onset of diffuse, generalized maculopapulovesicular rash (i.e. spots, papules and/or vesicles) without other apparent cause] at least in the opinion of the investigator and was confirmed by laboratory test [Polymerase Chain Reaction (PCR) (+)] OR a case that met the clinical definition confirmed by the Independent Data Monitoring Committee (IDMC) and was epidemiologically linked [Epi (+)] to a valid index case.	From 42 days post dose 2 until the end of Phase A
Secondary	Phase A: Number of Subjects With Moderate or Severe Confirmed Varicella Case	Confirmed varicella case: A case that met the clinical case definition at least in the opinion of the investigator and was confirmed by laboratory test [PCR (+)] OR a case that met the clinical definition confirmed by the IDMC and was epidemiologically linked [Epi (+)] to a valid index case. Moderately severe disease: 8-15 points; severe disease: = 16 points (scored by IDMC using the modified Vázquez scale).	From 42 days post dose 2 until the end of Phase A
Secondary	Phase A: Number of Subjects With Probable or Confirmed Varicella Case	Probable or confirmed varicella case = A case that met the clinical case definition (as determined by the IDMC) but was not laboratory confirmed [PCR (-)] AND was not epidemiologically linked [Epi (-)] to another probable or confirmed case.	From 42 days post dose 2 until the end of Phase A
Secondary	Phase A: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations	Anti-VZV antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Secondary	Phase A: Number of Subjects With Seroconversion/Seroresponse to VZV	Seronegative (S-) = Subjects with antibody concentration less than (<) 25 mIU/mL prior to vaccination. Seropositive (S+) = Subjects with antibody concentration greater than or equal to (=) 25 mIU/mL prior to vaccination. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Secondary	Phase A: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations in a Subset of Subjects	Anti-measles antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Secondary	Phase A: Number of Subjects With Seroconversion/Seroresponse to Measles in a Subset of Subjects	Seronegative (S-) = Subjects with antibody concentration < 150 mIU/mL prior to vaccination. Seropositive (S+) = Subjects with antibody concentration = 150 mIU/mL prior to vaccination. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Secondary	Phase A: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations in a Subset of Subjects	Anti-mumps antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in units per milliliter (U/mL).	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Secondary	Phase A: Number of Subjects With Seroconversion/Seroresponse to Mumps in a Subset of Subjects	Seronegative (S-) = Subjects with antibody concentration < 231 U/mL prior to vaccination. Seropositive (S+) = Subjects with antibody concentration = 231 U/mL prior to vaccination. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Secondary	Phase A: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations in a Subset of Subjects	Anti-rubella antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in International Units per milliliter (IU/mL).	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Secondary	Phase A: Number of Subjects With a Seroconversion/Seroresponse to Rubella in a Subset of Subjects	Seronegative (S-) = Subjects with antibody concentration < 4 IU/mL prior to vaccination. Seropositive (S+) = Subjects with antibody concentration = 4 IU/mL prior to vaccination. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.	At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
Secondary	Phase A: Number of Subjects With Confirmed Cases of Herpes Zoster	The number of subjects with confirmed cases of herpes zoster is reported.	From Day 0 until the end of Phase A (Year 2)
Secondary	Phase A: Number of Subjects Reporting Fever	All fever = Occurrence of any fever (measured rectally) regardless of its intensity grade or relationship to vaccination. Related = fever (measured rectally) assessed by the investigator to be causally related to the study vaccination. Medical Advice = seek for medical advice.	Within 43 days (Day 0-42) post-vaccination period following each dose
Secondary	Phase A: Number of Subjects Reporting Fever	All fever = Occurrence of any fever (measured rectally) regardless of its intensity grade or relationship to vaccination. Related fever = fever (measured rectally) assessed by the investigator to be causally related to the study vaccination. Medical Advice = seek for medical advice.	Within 15 days (Day 0-14) post-vaccination period following each dose
Secondary	Phase A: Number of Subjects Reporting Solicited Local Symptoms	Solicited local symptoms assessed were pain, redness and swelling. Any solicited local symptom = Occurrence of any local symptom regardless of their intensity grade. Grade 3 pain = Cried when limb was moved/spontaneously painful. Grade 3 redness and swelling = greater than (>) 20 mm.	4 days post-vaccination period following each dose
Secondary	Phase A: Number of Subjects Reporting Meningism	Any = Occurrence of meningism regardless of its intensity grade. Grade 3 meningism = Prevented normal, everyday activities. Related = Assessed by the investigator to be causally related to the study vaccination.	Within 43 days (Day 0-42) post-vaccination period following each dose
Secondary	Phase A: Number of Subjects Reporting Parotitis	Any = Occurrence of parotitis regardless of its intensity grade. Grade 3 parotitis = Swelling with accompanying general symptoms. Related = Assessed by the investigator to be causally related to the study.	Within 43 days (Day 0-42) post-vaccination period following each dose
Secondary	Phase A: Number of Subjects Reporting Rash	Any = Occurrence of rash regardless of its intensity grade. Grade 3 rash = 101-500 lesions. Grade 4 rash = > 500 lesions. Related rash = Assessed by the investigator to be causally related to the study vaccination.	Within 43 days (Day 0-42) post-vaccination period following each dose
Secondary	Phase A: Number of Subjects With Suspected Sign of Meningism Including Febrile Convulsions	Any = Occurrence of meningism including febrile convulsions regardless of intensity grade.	Within 43 days (Day 0-42) post-vaccination period following each dose
Secondary	Phase A: Number of Subjects Reporting Unsolicited Adverse Events (AEs)	Unsolicited AE assessed included any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = Occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.	Within 43 days (Day 0-42) post-vaccination period following each dose
Secondary	Phase A: Number of Subjects Reporting Serious Adverse Events (SAEs)	SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalisation or prolongation of hospitalisation or resulted in disability/incapacity. Any SAE = occurrence of SAE regardless of intensity grade or relation to vaccination.	From Day 0 until the end of Phase A (Year 2)
Secondary	Phase A: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness	Parameters assessed: 1. Number of hours lost from work by parents/guardians as a result of taking care of their child due to varicella. 2. Number of hours the child lost attendance in: day care/childminder, school, or in any extra-curricular activities (e.g. sports or recreation or any type of organised leisure activities) due to varicella. 3. Number of hours spent by a nurse, a babysitter or any type of existing paid caregiver to look after the child (if applicable).	During Phase A (from Day 0 up to Year 2)
Secondary	Phase B: Number of Subjects With Confirmed Varicella Case	Confirmed varicella case = A case that met the clinical case definition at least in the opinion of the investigator and was confirmed by laboratory test [PCR (+)] OR a case that met the clinical definition confirmed by the IDMC and was epidemiologically linked [Epi (+)] to a valid index case.	From the beginning of Phase B (Year 2) up to study end (Year 10)
Secondary	Phase B: Number of Subjects With Moderate or Severe Confirmed Varicella Case	Confirmed varicella case = A case that met the clinical case definition at least in the opinion of the investigator and was confirmed by laboratory test [PCR (+)] OR a case that met the clinical definition confirmed by the IDMC and was epidemiologically linked [Epi (+)] to a valid index case. Moderately severe disease = 8-15 points; severe disease: = 16 points (scored by IDMC using the modified Vázquez scale).	From the beginning of Phase B (Year 2) up to study end (Year 10)
Secondary	Phase B: Number of Subjects With Probable or Confirmed Varicella Case	Probable or confirmed varicella = A case that met the clinical case definition (as determined by the IDMC) but was not laboratory confirmed [PCR (-)] AND was not epidemiologically linked [Epi (-)] to another probable or confirmed case.	From the beginning of Phase B (Year 2) up to study end (Year 10)
Secondary	Phase B: Characteristics of Varicella Cases	Varicella cases were characterized by type, number and character of lesions, duration of rash, incidence of fever, systemic signs, the assessment by investigator, complications, treatment, outcome and intensity of severity.	From the beginning of Phase B (Year 2) up to study end (Year 10)
Secondary	Phase B: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations	Anti-VZV antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).	At Year 4, Year 6, Year 8 and Year 10 time points
Secondary	Phase B: Number of Subjects With Anti-VZV Antibody Concentrations Above the Cut-off Value	The anti-VZV antibody concentration cut-off value assessed was greater than or equal to (=) 25 mIU/mL, in the sera of subjects seronegative before vaccination.	At Year 4, Year 6, Year 8 and Year 10 time points
Secondary	Phase B: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations	Anti-measles antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).	At Year 4, Year 6, Year 8 and Year 10 time points
Secondary	Phase B: Number of Subjects With Anti-measles Antibody Concentrations Above the Cut-off Value	The anti-measles antibody concentration cut-off value assessed was = 150 mIU/mL, in the sera of subjects seronegative before vaccination.	At Year 4, Year 6, Year 8 and Year 10 time points
Secondary	Phase B: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations	Anti-mumps antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in units per milliliter (U/mL).	At Year 4, Year 6, Year 8 and Year 10 time points
Secondary	Phase B: Number of Subjects With Anti-mumps Antibody Concentrations Above the Cut-off Value	The anti-mumps antibody concentration cut-off value assessed was = 231 U/mL, in the sera of subjects seronegative before vaccination.	At Year 4, Year 6, Year 8 and Year 10 time points
Secondary	Phase B: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations	Anti-rubella antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in international units per milliliter (IU/mL).	At Year 4, Year 6, Year 8 and Year 10 time points
Secondary	Phase B: Number of Subjects With Anti-rubella Antibody Concentrations Above the Cut-off Value	The anti-rubella antibody concentration cut-off value assessed was = 4 IU/mL, in the sera of subjects seronegative before vaccination.	At Year 4, Year 6, Year 8 and Year 10 time points
Secondary	Phase B: Characteristics of Zoster Cases	Zoster cases were characterized by number and character of lesions, duration of rash, incidence of fever, systemic signs, the assessment by investigator, complications, treatment, outcome and intensity of severity.	From 6 weeks after Dose 2 until study end (Year 10)
Secondary	Phase B: Number of Subjects Reporting Serious Adverse Events (SAEs)	SAEs assessed included medical occurrences that resulted in death, were life-threatening, required hospitalisation or prolongation of hospitalisation or resulted in disability/incapacity. Any SAE = occurrence of SAE regardless of intensity grade or relation to vaccination.	From the beginning of Phase B (Year 2) up to study end (Year 10)
Secondary	Phase B: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness	Parameters assessed: 1. Number of hours lost from work by parents/guardians as a result of taking care of their child due to varicella. 2. Number of hours the child lost attendance in: day care/childminder, school, or in any extra-curricular activities (e.g. sports or recreation or any type of organised leisure activities) due to varicella. 3. Number of hours spent by a nurse, a babysitter or any type of existing paid caregiver to look after the child (if applicable).	During Phase B

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