Immunogenicity and Safety of Kinrix + (Measles Mumps Rubella) MMR Vaccine With and Without Varicella Vaccine in Healthy Children 4-6 Years - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00871117

Purpose

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.

Condition	Intervention	Phase
Diphtheria Pertussis and/or Poliomyelitis Diseases Tetanus	Biological: GSK Biologicals'Kinrix® Biological: Merck and Company's MMRII Biological: Merck and Company's Varivax	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Immunogenicity and Safety Study of Kinrix® Co-administered With Varivax®

Resource links provided by NLM:

MedlinePlus related topics: Chickenpox Diphtheria Measles Mumps Polio and Post-Polio Syndrome Rubella Shingles Tetanus Whooping Cough

Drug Information available for: Chickenpox Vaccine

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Number of Subjects With Booster Responses to Diphteria and Tetanus [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Anti-diphteria (anti-D) and anti-tetanus (anti-T) booster response was defined as:
- initially seronegative subjects (sero-) (pre-booster antibody concentration below cut-off of < 0.1 international units per milliliter (IU/mL)) with an increase of at least four times the cut-off one month after vaccination (post-booster antibody concentration ≥0.4 IU/mL)
- initially seropositive subjects (sero+) (pre-booster antibody concentration ≥0.1 IU/mL) with an increase of at least four times the pre-booster antibody concentration one month after vaccination
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) [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
anti-PT, anti-FHA and anti-PRN booster response :
- initially sero- (pre-booster antibody concentration below cut-off < 5.0 EL.U/mL) with increase of at least four times cut-off one month after vaccination (concentration post-booster ≥20.0 EL.U/mL)
- initially sero+ with pre-booster antibody concentration ≥5.0 EL.U/mL and < 20.0 EL.U/mL with increase of at least four times pre-booster concentration one month post-booster
- initially sero+ with pre-booster antibody concentration ≥20.0 EL.U/mL with an increase of at least two times the pre-booster antibody concentration one month post-booster
Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3 [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Titers are expressed as GMTs.

Secondary Outcome Measures:

Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Cut-off value was defined as greater than or equal to 1.0 international units per milliliter (IU/mL).
Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Concentrations were expressed as GMCs in IU/mL.
GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Concentrations are expressed as GMCs in Enzyme-Linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
Number of Subjects With an Anti-polio 1, 2, 3 Booster Response [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Anti-poliovirus 1, anti-poliovirus 2 and anti-poliovirus 3 booster response:
- initially seronegative subjects (pre-booster antibody titer below cut-off of 8 ED50) with an antibody titer ≥ 32 ED50 one month after vaccination
- initially seropositive subjects (pre-booster antibody titers ≥ 8 ED50) with an increase at least four times the pre-booster antibody titer one month after vaccination.
ED50 is defined here as the reverse of the dilution resulting in 50% inhibition. The lowest dilution at which serum samples were tested is 1:8 from which a test was considered positive.
Number of Subjects Seroprotected Against Diphteria and Tetanus [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Seroprotection status was defined as:
- anti-D antibody concentration greater than or equal to 0.1 IU/mL
- anti-T antibody concentration greater than or equal to 0.1 IU/mL
Number of Subjects Protected Against Poliovirus 1, 2 and 3 [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Seroprotection was defined:

* anti-poliovirus type 1, 2 or 3 antibody titer greater than or equal to 8 ED50.

ED50 is defined here as the reverse of the dilution resulting in 50% inhibition.
Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ] [ Designated as safety issue: No ]
Seropositivity was defined as a concentration greater than or equal to 5.0 EL.U/mL
Number of Subjects With Solicited Local and General Symptoms [ Time Frame: Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax ] [ Designated as safety issue: No ]
Solicited local symptoms included pain, redness and swelling at the injection site. Solicited general symptoms included fever (temperature equal to or greater than 37.5 degrees Celsius), drowsiness and loss of appetite.
Number of Subjects With Unsolicited Adverse Events [ Time Frame: Up to 31 days (Day 0 through Day 30) after booster vaccination * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax ] [ Designated as safety issue: No ]
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.
Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (from Day 0 to 6 months post-vaccination) ] [ Designated as safety issue: No ]
Serious adverse events are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

Enrollment:	478
Study Start Date:	March 2009
Study Completion Date:	January 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Kinrix + M-M-R II + Varivax Subjects received at Day 0 one dose of Kinrix, intramuscularly in the deltoid region of the left upper arm, co-administered with one dose of M-M-R II and Varivax each, subcutaneously in the deltoid of the right upper and lower arm, respectively.	Biological: GSK Biologicals'Kinrix® One dose as intramuscular injection at visit 1 Biological: Merck and Company's MMRII One dose as subcutaneous injection at visit 1 Biological: Merck and Company's Varivax One dose as subcutaneous injection at visit 1 or at visit 2
Active Comparator: Kinrix + M-M-R II -> Varivax Subjects received at Day 0 one dose of Kinrix, intramuscularly in the deltoid region of the left upper arm, co-administered with one dose of M-M-R II, subcutaneously in the deltoid of the right upper arm. At Day 30 they received one dose of Varivax subcutaneously in the deltoid region of the right upper arm.	Biological: GSK Biologicals'Kinrix® One dose as intramuscular injection at visit 1 Biological: Merck and Company's MMRII One dose as subcutaneous injection at visit 1 Biological: Merck and Company's Varivax One dose as subcutaneous injection at visit 1 or at visit 2

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

Ages Eligible for Study:	4 Years to 6 Years
Genders Eligible for Study:	Both
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.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00871117

Locations

United States, California
GSK Investigational Site
Antioch, California, United States, 94509
GSK Investigational Site
Daly City, California, United States, 94015
GSK Investigational Site
Hayward, California, United States, 94545
GSK Investigational Site
Redwood City, California, United States, 94063
GSK Investigational Site
Roseville, California, United States, 95661
GSK Investigational Site
Sacramento, California, United States, 95823
GSK Investigational Site
Sacramento, California, United States, 95815
GSK Investigational Site
San Jose, California, United States, 95119
GSK Investigational Site
Santa Rosa, California, United States, 95403
GSK Investigational Site
Vallejo, California, United States, 94589
GSK Investigational Site
Walnut Creek, California, United States, 94596

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00871117 History of Changes
Other Study ID Numbers:	111852
Study First Received:	March 26, 2009
Results First Received:	January 13, 2011
Last Updated:	February 17, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

Co-administration
Immunization
Preschool
Booster

Additional relevant MeSH terms:

Diphtheria
Whooping Cough
Poliomyelitis
Tetanus
Corynebacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bordetella Infections
Gram-Negative Bacterial Infections
Respiratory Tract Infections
Infection
Respiratory Tract Diseases

Myelitis
Central Nervous System Viral Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Spinal Cord Diseases
Neuromuscular Diseases
Clostridium Infections

ClinicalTrials.gov processed this record on May 23, 2012