Clinical trial NCT00226499: Evaluate Vaccine Against Chickenpox and a Combined Vaccine Against 4 Viral Childhood Diseases: Measles, Mumps, Rubella and Chickenpox
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Varicella
Chickenpox Vaccines
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-27
Enrollment: 5803
Sex: ALL
Minimum age (years): 11
Maximum age (years): 22
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Phase A: Number of Subjects With Confirmed Varicella Case
timeFrame: From 42 days post dose 2 until the end of Phase A
Secondary outcomes:
measure: Phase A: Number of Subjects With Moderate or Severe Confirmed Varicella Case
timeFrame: From 42 days post dose 2 until the end of Phase A
measure: Phase A: Number of Subjects With Probable or Confirmed Varicella Case
timeFrame: From 42 days post dose 2 until the end of Phase A
measure: Phase A: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations
timeFrame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
measure: Phase A: Number of Subjects With Seroconversion/Seroresponse to VZV
timeFrame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
measure: Phase A: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations in a Subset of Subjects
timeFrame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
measure: Phase A: Number of Subjects With Seroconversion/Seroresponse to Measles in a Subset of Subjects
timeFrame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
measure: Phase A: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations in a Subset of Subjects
timeFrame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
measure: Phase A: Number of Subjects With Seroconversion/Seroresponse to Mumps in a Subset of Subjects
timeFrame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
measure: Phase A: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations in a Subset of Subjects
timeFrame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
measure: Phase A: Number of Subjects With a Seroconversion/Seroresponse to Rubella in a Subset of Subjects
timeFrame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points
measure: Phase A: Number of Subjects With Confirmed Cases of Herpes Zoster
timeFrame: From Day 0 until the end of Phase A (Year 2)
measure: Phase A: Number of Subjects Reporting Fever
timeFrame: Within 43 days (Day 0-42) post-vaccination period following each dose
measure: Phase A: Number of Subjects Reporting Fever
timeFrame: Within 15 days (Day 0-14) post-vaccination period following each dose
measure: Phase A: Number of Subjects Reporting Solicited Local Symptoms
timeFrame: 4 days post-vaccination period following each dose
measure: Phase A: Number of Subjects Reporting Meningism
timeFrame: Within 43 days (Day 0-42) post-vaccination period following each dose
measure: Phase A: Number of Subjects Reporting Parotitis
timeFrame: Within 43 days (Day 0-42) post-vaccination period following each dose
measure: Phase A: Number of Subjects Reporting Rash
timeFrame: Within 43 days (Day 0-42) post-vaccination period following each dose
measure: Phase A: Number of Subjects With Suspected Sign of Meningism Including Febrile Convulsions
timeFrame: Within 43 days (Day 0-42) post-vaccination period following each dose
measure: Phase A: Number of Subjects Reporting Unsolicited Adverse Events (AEs)
timeFrame: Within 43 days (Day 0-42) post-vaccination period following each dose
measure: Phase A: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: From Day 0 until the end of Phase A (Year 2)
measure: Phase A: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness
timeFrame: During Phase A (from Day 0 up to Year 2)
measure: Phase B: Number of Subjects With Confirmed Varicella Case
timeFrame: From the beginning of Phase B (Year 2) up to study end (Year 10)
measure: Phase B: Number of Subjects With Moderate or Severe Confirmed Varicella Case
timeFrame: From the beginning of Phase B (Year 2) up to study end (Year 10)
measure: Phase B: Number of Subjects With Probable or Confirmed Varicella Case
timeFrame: From the beginning of Phase B (Year 2) up to study end (Year 10)
measure: Phase B: Characteristics of Varicella Cases
timeFrame: From the beginning of Phase B (Year 2) up to study end (Year 10)
measure: Phase B: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations
timeFrame: At Year 4, Year 6, Year 8 and Year 10 time points
measure: Phase B: Number of Subjects With Anti-VZV Antibody Concentrations Above the Cut-off Value
timeFrame: At Year 4, Year 6, Year 8 and Year 10 time points
measure: Phase B: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations
timeFrame: At Year 4, Year 6, Year 8 and Year 10 time points
measure: Phase B: Number of Subjects With Anti-measles Antibody Concentrations Above the Cut-off Value
timeFrame: At Year 4, Year 6, Year 8 and Year 10 time points
measure: Phase B: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations
timeFrame: At Year 4, Year 6, Year 8 and Year 10 time points
measure: Phase B: Number of Subjects With Anti-mumps Antibody Concentrations Above the Cut-off Value
timeFrame: At Year 4, Year 6, Year 8 and Year 10 time points
measure: Phase B: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations
timeFrame: At Year 4, Year 6, Year 8 and Year 10 time points
measure: Phase B: Number of Subjects With Anti-rubella Antibody Concentrations Above the Cut-off Value
timeFrame: At Year 4, Year 6, Year 8 and Year 10 time points
measure: Phase B: Characteristics of Zoster Cases
timeFrame: From 6 weeks after Dose 2 until study end (Year 10)
measure: Phase B: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: From the beginning of Phase B (Year 2) up to study end (Year 10)
measure: Phase B: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness
timeFrame: During Phase B
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Chomutov
country: Czechia
facility: GSK Investigational Site
city: Decin
country: Czechia
facility: GSK Investigational Site
city: Havlickuv Brod
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Humpolec
country: Czechia
facility: GSK Investigational Site
city: Jindrichuv Hradec
country: Czechia
facility: GSK Investigational Site
city: Kolin
country: Czechia
facility: GSK Investigational Site
city: Liberec
country: Czechia
facility: GSK Investigational Site
city: Moravska Ostrava
country: Czechia
facility: GSK Investigational Site
city: Nachod
country: Czechia
facility: GSK Investigational Site
city: Ostrava
country: Czechia
facility: GSK Investigational Site
city: Pardubice
country: Czechia
facility: GSK Investigational Site
city: Plzen
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Praha 5
country: Czechia
facility: GSK Investigational Site
city: Praha 6
country: Czechia
facility: GSK Investigational Site
city: Praha 9
country: Czechia
facility: GSK Investigational Site
city: Znojmo
country: Czechia
facility: GSK Investigational Site
city: Arta
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Giannitsa
country: Greece
facility: GSK Investigational Site
city: Karditsa
country: Greece
facility: GSK Investigational Site
city: Komotini
country: Greece
facility: GSK Investigational Site
city: Ptolemaida
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Tripolis
country: Greece
facility: GSK Investigational Site
city: Veria
country: Greece
facility: GSK Investigational Site
city: Quarto (NA)
country: Italy
facility: GSK Investigational Site
state: Campania
city: Ferrara
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Udine
country: Italy
facility: GSK Investigational Site
state: Friuli-Venezia-Giulia
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Novara
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Alghero (SS)
country: Italy
facility: GSK Investigational Site
state: Sardegna
city: Ozieri (SS)
country: Italy
facility: GSK Investigational Site
state: Sardegna
city: Firenze
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Alytus
country: Lithuania
facility: GSK Investigational Site
city: Kaunas
country: Lithuania
facility: GSK Investigational Site
city: Klaipeda
country: Lithuania
facility: GSK Investigational Site
city: Panevezys
country: Lithuania
facility: GSK Investigational Site
city: Siauliai
country: Lithuania
facility: GSK Investigational Site
city: Vilnius
country: Lithuania
facility: GSK Investigational Site
city: Vilnius
country: Lithuania
facility: GSK Investigational Site
city: Vilnius
country: Lithuania
facility: GSK Investigational Site
city: Bekkestua
country: Norway
facility: GSK Investigational Site
city: Moelv
country: Norway
facility: GSK Investigational Site
city: Paradis
country: Norway
facility: GSK Investigational Site
city: Skien
country: Norway
facility: GSK Investigational Site
city: Trondheim
country: Norway
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Debica
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Olesnica
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Siemianowice Slaskie
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Trzebnica
country: Poland
facility: GSK Investigational Site
city: Wesola
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Sibiu
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Ivanteevka Moscow Region
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Murmansk
country: Russian Federation
facility: GSK Investigational Site
city: Novokuznetsk
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: Sankt-Peterburg
country: Russian Federation
facility: GSK Investigational Site
city: Saratov
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Volgograd
country: Russian Federation
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Dlha nad Oravou
country: Slovakia
facility: GSK Investigational Site
city: Dolny Kubin
country: Slovakia
facility: GSK Investigational Site
city: Dubnica Nad Vahom
country: Slovakia
facility: GSK Investigational Site
city: Nova Dubnica
country: Slovakia
facility: GSK Investigational Site
city: Nove Mesto nad Vahom
country: Slovakia
facility: GSK Investigational Site
city: Nove Zamky
country: Slovakia
facility: GSK Investigational Site
city: Puchov
country: Slovakia
facility: GSK Investigational Site
city: Ruzomberok
country: Slovakia
facility: GSK Investigational Site
city: Sturovo
country: Slovakia
facility: GSK Investigational Site
city: Surany
country: Slovakia
facility: GSK Investigational Site
city: Trencin
country: Slovakia
facility: GSK Investigational Site
city: Linköping
country: Sweden
facility: GSK Investigational Site
city: Malmö
country: Sweden
facility: GSK Investigational Site
city: Norrköping
country: Sweden
facility: GSK Investigational Site
city: Umeå
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
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.
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):1313-1324. doi: 10.1016/S0140-6736(12)61461-5. Epub 2014 Jan 29.
citation: 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.
citation: Habib MA, Prymula R, Carryn S, Esposito S, Henry O, Ravault S, Usonis V, Wysocki J, Gillard P, Povey M. Correlation of protection against varicella in a randomized Phase III varicella-containing vaccine efficacy trial in healthy infants. Vaccine. 2021 Jun 8;39(25):3445-3454. doi: 10.1016/j.vaccine.2021.02.074. Epub 2021 Mar 16.
citation: Povey M, Henry O, Riise Bergsaker MA, Chlibek R, Esposito S, Flodmark CE, Gothefors L, Man S, Silfverdal SA, Stefkovicova M, Usonis V, Wysocki J, Gillard P, Prymula R. Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: 10-year follow-up of a phase 3 multicentre, observer-blind, randomised, controlled trial. Lancet Infect Dis. 2019 Mar;19(3):287-297. doi: 10.1016/S1473-3099(18)30716-3. Epub 2019 Feb 11.