Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00226499
Recruitment Status : Completed
First Posted : September 27, 2005
Results First Posted : September 23, 2019
Last Update Posted : September 23, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Varicella Chickenpox Vaccines Biological: Priorix-tetra™ Biological: Priorix™ Biological: Varilrix™ Phase 3

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5803 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : September 1, 2005
Actual Primary Completion Date : October 12, 2006
Actual Study Completion Date : October 12, 2006

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MMRV Group
Subjects in this group received 2 doses of Priorix-Tetra vaccine, administered subcutaneously in the deltoid region of the left arm, one at Day 0 (Visit 1) and the other at Day 42 (Visit 2).
Biological: Priorix-tetra™
2 doses administered subcutaneously, one at Day 0 and the other at Day 42 to subjects in MMRV Group

Experimental: OKAH Group
Subjects in this group received 1 dose of Priorix at Day 0 (Visit 1) and 1 dose of Varilrix at Day 42 (Visit 2). Both vaccines were administered subcutaneously in the deltoid region of the left arm.
Biological: 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

Biological: Varilrix™
1 dose administered subcutaneously at Day 42 to subjects in OKAH Group

Active Comparator: MMR Group
Subjects in this group received 2 doses of Priorix, administered subcutaneously in the deltoid region of the left arm, one at Day 0 (Visit 1) and the other at Day 42 (Visit 2).
Biological: 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




Primary Outcome Measures :
  1. Phase A: Number of Subjects With Confirmed Varicella Case [ Time Frame: From 42 days post dose 2 until the end of Phase A ]
    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.


Secondary Outcome Measures :
  1. Phase A: Number of Subjects With Moderate or Severe Confirmed Varicella Case [ Time Frame: From 42 days post dose 2 until the end of Phase A ]
    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).

  2. Phase A: Number of Subjects With Probable or Confirmed Varicella Case [ Time Frame: From 42 days post dose 2 until the end of Phase A ]
    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.

  3. Phase A: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations [ Time Frame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points ]
    Anti-VZV antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).

  4. Phase A: Number of Subjects With Seroconversion/Seroresponse to VZV [ Time Frame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points ]
    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.

  5. Phase A: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations in a Subset of Subjects [ Time Frame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points ]
    Anti-measles antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).

  6. Phase A: Number of Subjects With Seroconversion/Seroresponse to Measles in a Subset of Subjects [ Time Frame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points ]
    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.

  7. Phase A: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations in a Subset of Subjects [ Time Frame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points ]
    Anti-mumps antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in units per milliliter (U/mL).

  8. Phase A: Number of Subjects With Seroconversion/Seroresponse to Mumps in a Subset of Subjects [ Time Frame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points ]
    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.

  9. Phase A: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations in a Subset of Subjects [ Time Frame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points ]
    Anti-rubella antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in International Units per milliliter (IU/mL).

  10. Phase A: Number of Subjects With a Seroconversion/Seroresponse to Rubella in a Subset of Subjects [ Time Frame: At Day 0, Day 42, Day 84, Year 1 and Year 2 time points ]
    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.

  11. Phase A: Number of Subjects With Confirmed Cases of Herpes Zoster [ Time Frame: From Day 0 until the end of Phase A (Year 2) ]
    The number of subjects with confirmed cases of herpes zoster is reported.

  12. Phase A: Number of Subjects Reporting Fever [ Time Frame: Within 43 days (Day 0-42) post-vaccination period following each dose ]
    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.

  13. Phase A: Number of Subjects Reporting Fever [ Time Frame: Within 15 days (Day 0-14) post-vaccination period following each dose ]
    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.

  14. Phase A: Number of Subjects Reporting Solicited Local Symptoms [ Time Frame: 4 days post-vaccination period following each dose ]
    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.

  15. Phase A: Number of Subjects Reporting Meningism [ Time Frame: Within 43 days (Day 0-42) post-vaccination period following each dose ]
    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.

  16. Phase A: Number of Subjects Reporting Parotitis [ Time Frame: Within 43 days (Day 0-42) post-vaccination period following each dose ]
    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.

  17. Phase A: Number of Subjects Reporting Rash [ Time Frame: Within 43 days (Day 0-42) post-vaccination period following each dose ]
    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.

  18. Phase A: Number of Subjects With Suspected Sign of Meningism Including Febrile Convulsions [ Time Frame: Within 43 days (Day 0-42) post-vaccination period following each dose ]
    Any = Occurrence of meningism including febrile convulsions regardless of intensity grade.

  19. Phase A: Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: Within 43 days (Day 0-42) post-vaccination period following each dose ]
    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.

  20. Phase A: Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: From Day 0 until the end of Phase A (Year 2) ]
    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.

  21. Phase A: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness [ Time Frame: During Phase A (from Day 0 up to Year 2) ]
    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).

  22. Phase B: Number of Subjects With Confirmed Varicella Case [ Time Frame: From the beginning of Phase B (Year 2) up to study end (Year 10) ]
    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.

  23. Phase B: Number of Subjects With Moderate or Severe Confirmed Varicella Case [ Time Frame: From the beginning of Phase B (Year 2) up to study end (Year 10) ]
    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).

  24. Phase B: Number of Subjects With Probable or Confirmed Varicella Case [ Time Frame: From the beginning of Phase B (Year 2) up to study end (Year 10) ]
    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.

  25. Phase B: Characteristics of Varicella Cases [ Time Frame: From the beginning of Phase B (Year 2) up to study end (Year 10) ]
    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.

  26. Phase B: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations [ Time Frame: At Year 4, Year 6, Year 8 and Year 10 time points ]
    Anti-VZV antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).

  27. Phase B: Number of Subjects With Anti-VZV Antibody Concentrations Above the Cut-off Value [ Time Frame: At Year 4, Year 6, Year 8 and Year 10 time points ]
    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.

  28. Phase B: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations [ Time Frame: At Year 4, Year 6, Year 8 and Year 10 time points ]
    Anti-measles antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milliinternational units per milliliter (mIU/mL).

  29. Phase B: Number of Subjects With Anti-measles Antibody Concentrations Above the Cut-off Value [ Time Frame: At Year 4, Year 6, Year 8 and Year 10 time points ]
    The anti-measles antibody concentration cut-off value assessed was ≥ 150 mIU/mL, in the sera of subjects seronegative before vaccination.

  30. Phase B: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations [ Time Frame: At Year 4, Year 6, Year 8 and Year 10 time points ]
    Anti-mumps antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in units per milliliter (U/mL).

  31. Phase B: Number of Subjects With Anti-mumps Antibody Concentrations Above the Cut-off Value [ Time Frame: At Year 4, Year 6, Year 8 and Year 10 time points ]
    The anti-mumps antibody concentration cut-off value assessed was ≥ 231 U/mL, in the sera of subjects seronegative before vaccination.

  32. Phase B: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations [ Time Frame: At Year 4, Year 6, Year 8 and Year 10 time points ]
    Anti-rubella antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in international units per milliliter (IU/mL).

  33. Phase B: Number of Subjects With Anti-rubella Antibody Concentrations Above the Cut-off Value [ Time Frame: At Year 4, Year 6, Year 8 and Year 10 time points ]
    The anti-rubella antibody concentration cut-off value assessed was ≥ 4 IU/mL, in the sera of subjects seronegative before vaccination.

  34. Phase B: Characteristics of Zoster Cases [ Time Frame: From 6 weeks after Dose 2 until study end (Year 10) ]
    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.

  35. Phase B: Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: From the beginning of Phase B (Year 2) up to study end (Year 10) ]
    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.

  36. Phase B: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness [ Time Frame: During Phase B ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   11 Months to 22 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00226499


  Show 104 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline

Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 100388
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 100388
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 100388
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 100388
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 100388
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 100388
For additional information about this study please refer to the GSK Clinical Study Register

Publications:
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00226499     History of Changes
Other Study ID Numbers: 100388
104105 (EXT FU Y2) ( Other Identifier: GSK )
103494 (EXT FU Y1) ( Other Identifier: GSK )
104106 (EXT FU Y4-Y6-Y8-Y10) ( Other Identifier: GSK )
2004-002676-41 ( EudraCT Number )
First Posted: September 27, 2005    Key Record Dates
Results First Posted: September 23, 2019
Last Update Posted: September 23, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Chickenpox
Herpes Zoster
Rubella
RNA Virus Infections
Virus Diseases
Varicella Zoster Virus Infection
Herpesviridae Infections
DNA Virus Infections
Rubivirus Infections
Togaviridae Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs