Evaluate Vaccine Against Chickenpox and a Combined Vaccine Against 4 Viral Childhood Diseases: Measles, Mumps, Rubella and Chickenpox
- Conditions
- Chickenpox VaccinesVaricella
- Interventions
- Biological: Priorix™Biological: Priorix-tetra™Biological: Varilrix™
- Registration Number
- NCT00226499
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5803
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OKAH Group Varilrix™ 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. MMR Group Priorix™ 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). MMRV Group Priorix-tetra™ 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). OKAH Group Priorix™ 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.
- Primary Outcome Measures
Name Time Method Phase A: Number of Subjects With Confirmed Varicella Case 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
Name Time Method Phase A: Number of Subjects With Seroconversion/Seroresponse to VZV 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.
Phase A: Number of Subjects With Moderate or Severe Confirmed Varicella Case 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).
Phase A: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations 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).
Phase A: Number of Subjects With Probable or Confirmed Varicella Case 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.
Phase A: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations in a Subset of Subjects 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).
Phase A: Number of Subjects With Suspected Sign of Meningism Including Febrile Convulsions Within 43 days (Day 0-42) post-vaccination period following each dose Any = Occurrence of meningism including febrile convulsions regardless of intensity grade.
Phase A: Number of Subjects Reporting Serious Adverse Events (SAEs) 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.
Phase A: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations in a Subset of Subjects 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).
Phase A: Number of Subjects With Seroconversion/Seroresponse to Mumps in a Subset of Subjects 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.
Phase A: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations in a Subset of Subjects 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).
Phase B: Number of Subjects With Probable or Confirmed Varicella Case 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.
Phase B: Number of Subjects With Anti-rubella Antibody Concentrations Above the Cut-off Value 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.
Phase B: Number of Subjects Reporting Serious Adverse Events (SAEs) 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.
Phase A: Number of Subjects With Seroconversion/Seroresponse to Measles in a Subset of Subjects 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.
Phase A: Number of Subjects With Confirmed Cases of Herpes Zoster From Day 0 until the end of Phase A (Year 2) The number of subjects with confirmed cases of herpes zoster is reported.
Phase A: Number of Subjects Reporting Solicited Local Symptoms 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.
Phase A: Number of Subjects Reporting Unsolicited Adverse Events (AEs) 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.
Phase B: Characteristics of Varicella Cases 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.
Phase B: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations 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).
Phase A: Number of Subjects With a Seroconversion/Seroresponse to Rubella in a Subset of Subjects 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.
Phase A: Number of Subjects Reporting Meningism 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.
Phase A: Number of Subjects Reporting Parotitis 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.
Phase A: Number of Subjects Reporting Rash 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.
Phase A: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness 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).
Phase B: Number of Subjects With Moderate or Severe Confirmed Varicella Case 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).
Phase B: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness 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).
Phase A: Number of Subjects Reporting Fever 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.
Phase B: Number of Subjects With Confirmed Varicella Case 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.
Phase B: Number of Subjects With Anti-VZV Antibody Concentrations Above the Cut-off Value 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.
Phase B: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations 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).
Phase B: Characteristics of Zoster Cases 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.
Phase B: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations 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).
Phase B: Number of Subjects With Anti-measles Antibody Concentrations Above the Cut-off Value 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.
Phase B: Number of Subjects With Anti-mumps Antibody Concentrations Above the Cut-off Value 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.
Phase B: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations 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).
Trial Locations
- Locations (1)
GSK Investigational Site
🇸🇪Örebro, Sweden