Clinical trial NCT00871117: Immunogenicity and Safety of Kinrix + (Measles Mumps Rubella) MMR Vaccine With and Without Varicella Vaccine in Healthy Children 4-6 Years
Official title: Immunogenicity and Safety Study of Kinrix® Co-administered With Varivax®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tetanus
Acellular Pertussis
Diphtheria
Keywords: Co-administration
Immunization
Preschool
Booster
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-03-30
Enrollment: 478
Sex: ALL
Minimum age (years): 4
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to evaluate the immunogenicity and safety of Kinrix when co-administered with varicella (Varivax® \[varicella virus vaccine live\], Merck and Company) and (measles mumps rubella) MMR vaccines, compared to Kinrix co-administered with MMR vaccine alone. Both Kinrix and the second dose of Varivax are indicated in children 4-6 years of age, and there is great potential for the vaccines to be given concurrently. The aim of this trial is to demonstrate that co-administered Varivax does not negatively affect the immunogenicity or reactogenicity of Kinrix.

Detailed description: Subjects 4-6 years of age will be randomized into two groups to receive either Kinrix, Varivax and M-M-RII on day 0 (Group 1) or Kinrix and M-M-RII on day 0 and Varivax at month 1(Group 2).

All subjects in both groups to provide blood samples prior to vaccination on day 0 and at month 1 (for Group 2, blood sampling is prior to vaccination with Varivax).

Duration of the study will be approximately 6 months for each subject with a safety telephone contact 6 months after vaccinations.

Eligibility criteria: Inclusion Criteria:

* Subjects for whom the investigator believes that their parents/ guardians can and will comply with the requirements of the protocol.
* A male or female child between 4 and 6 years of age, inclusive.
* Written informed consent obtained from the parent or guardian of the subject.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Having received 4 doses of (Diphtheria, Tetanus Acellular Pertussis) DTaP vaccine using Pediarix and/or Infanrix, and 3 doses of poliovirus vaccine using Pediarix and/or (inactivated poliovirus vaccine, Aventis Pasteur) IPOL in the first 2 years of life.
* Previously received 1 dose of M-M-RII and Varivax (separate or combined) in the second year of life.

Exclusion Criteria:

* Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding the administration of study vaccines, or planned use during the study period.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or non-investigational product or device.
* History of previous or intercurrent diphtheria, tetanus, pertussis, polio, measles, mumps, rubella or varicella disease, or of vaccination against these diseases given after the second year of life.
* Known exposure to diphtheria, tetanus, pertussis, or polio, prior to vaccination.
* Poliovirus vaccination with one or more doses of (oral polio virus) OPV vaccine.
* Administration or planned administration of a vaccine not foreseen by the study protocol within 30 days of study vaccination and ending at Day 30.
* Chronic administration or planned administration of immunosuppressants or other immune modifying drugs within six months prior to study vaccination or planned administration during the study period ending at Day 30.
* Administration of immunoglobulins and/or any blood products at any time prior to study vaccination or planned administration during the study period ending at Day 30.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
* History of seizures or progressive neurological disorder, including infantile spasms, uncontrolled epilepsy or progressive encephalopathy.
* Major congenital defects or serious chronic illness.
* Acute disease at the time of enrolment.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
* History of anaphylactic reaction to egg proteins or previous doses of the vaccine(s).
* Encephalopathy within 7 days of administration of previous dose of Infanrix or Pediarix.
* Fever \>=40.5°C or 104.9°F (rectal temperature) (39.5°C or 103.1°F, oral/axillary) within 48 hours of previous dose of Infanrix or Pediarix not due to another identifiable cause.
* Collapse or shock-like state within 48 hours of previous dose of DTaP or DTaP-containing vaccine.
* Persistent, severe, inconsolable screaming or crying lasting ³3 hours occurring within 48 hours of administration of previous dose of DTaP or DTaP-containing vaccine.
* Thrombocytopenia following a previous dose of M-M-RII or its component vaccines
* Inability to contact a parent/guardian of the subject by telephone.
* Blood dyscrasias, leukemia, lymphomas or other malignant neoplasms affecting the bone marrow or lymphatic systems.
* Family history of congenital or hereditary immunodeficiency, unless the immune competence of the subject has been demonstrated.
* Residence in the same household as the following persons:
* New-born infants (0-4 weeks of age).
* Pregnant mother/women without documented positive history of chickenpox disease or laboratory evidence of prior varicella vaccination.
* Pregnant women at or beyond 28 weeks gestation regardless of varicella vaccination status or varicella disease history.
* Persons with known immunodeficiency.
* Active untreated tuberculosis.

Primary outcomes:
measure: Number of Subjects With Booster Responses to Diphteria and Tetanus
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL)
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Secondary outcomes:
measure: Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: Number of Subjects With an Anti-polio 1, 2, 3 Booster Response
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: Number of Subjects Seroprotected Against Diphteria and Tetanus
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: Number of Subjects Protected Against Poliovirus 1, 2 and 3
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies
timeFrame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
measure: Number of Subjects With Any Solicited Local Symptoms
timeFrame: Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
measure: Number of Subjects With Any Solicited General Symptoms
timeFrame: Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
measure: Number of Subjects With Unsolicited Adverse Events
timeFrame: Up to 31 days (Day 0 through Day 30) after booster vaccination * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (from Day 0 to 6 months post-vaccination)
Other outcomes:
Locations:
city: Antioch
country: United States
facility: GSK Investigational Site
state: California
city: Daly City
country: United States
facility: GSK Investigational Site
state: California
city: Hayward
country: United States
facility: GSK Investigational Site
state: California
city: Redwood City
country: United States
facility: GSK Investigational Site
state: California
city: Roseville
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: San Jose
country: United States
facility: GSK Investigational Site
state: California
city: Santa Rosa
country: United States
facility: GSK Investigational Site
state: California
city: Vallejo
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Klein NP, Weston WM, Kuriyakose S, Kolhe D, Howe B, Friedland LR, Van Der Meeren O. An open-label, randomized, multi-center study of the immunogenicity and safety of DTaP-IPV (Kinrix) co-administered with MMR vaccine with or without varicella vaccine in healthy pre-school age children. Vaccine. 2012 Jan 11;30(3):668-74. doi: 10.1016/j.vaccine.2011.10.065. Epub 2011 Nov 4.