Clinical trial NCT00148941: Immune Response and Safety Comparison of 3 Lots of GSK Biologicals' DTaP-IPV Candidate Vaccine to DTaP + IPV Vaccines
Official title: Safety, Immunogenicity and Consistency of 3 Manufacturing Lots of DTaP-IPV Vaccine Versus Separate Injections of GSK Biologicals' DTaP + Aventis Pasteur's IPV Administered as Booster Doses to Healthy Children 4-6 Years, Each Co-administered With Merck's MMR Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tetanus
Acellular Pertussis
Diphtheria
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-08
Enrollment: 4209
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 aims of this trial are to demonstrate the consistency of three manufacturing lots of GSK Biologicals' DTaP-IPV candidate vaccine in terms of immunogenicity and to evaluate the non-inferiority of GSK Biologicals' DTaP-IPV vaccine with respect to immunogenicity and safety compared to the control vaccines (separate injections of GSK Biologicals' DTaP vaccine \[Infanrix\] and Aventis Pasteur's IPV vaccine \[IPOL\]) when administered as a 5th dose of DTaP and a 4th dose of inactivated poliovirus vaccine in subjects 4 to 6 years of age. Vaccines will be co-administered with the second dose of M-M-RII, which is recommended at this age. Concomitant administration of a US-licensed influenza vaccine will be allowed according to seasonal availability of vaccine and at the discretion of the investigator.

Detailed description: * Investigational groups: 3, each receive one of 3 lots of DTaP-IPV vaccine.
* Control: US-licensed DTaP (Infanrix) + US-licensed IPV (IPOL) vaccines administered in separate injections.
* Two study visits one month apart for a subset of subjects (Safety and Immunogenicity subset) with a blood draw at each visit. All other subjects will have one visit.
* A telephone contact 4-6 days after vaccination for all subjects, a telephone contact 31-38 days after vaccination for the Safety only subset and a telephone contact for all subjects during the extended safety follow-up phase (5 months following the active phase).

Eligibility criteria: Inclusion criteria:

* Male or female child between and including 4 and 6 years of age at the time of vaccination.
* Free of obvious health problems as established by medical history and brief medical evaluation before entering into the study.
* Received 4 doses of Infanrix and 3 doses of IPOL during the first 2 years of life.
* Vaccination against measles, mumps, and rubella in the second year of life.
* Subjects whom the investigator believed would comply with the requirements of the protocol.
* Written informed consent obtained before study entry from the parent(s) or guardian(s) of the subject.

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.
* History of previous or intercurrent diphtheria, tetanus, pertussis, polio, measles, mumps, or rubella 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 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 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 within three months 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 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 enrollment.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s), including allergic reactions to 2-phenoxyethanol, formaldehyde, neomycin, polymyxin B, streptomycin, gelatin, and/or latex.
* 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.
* 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 not due to another identifiable cause.
* Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of previous dose of Infanrix.
* Persistent, severe, inconsolable screaming or crying lasting ≥ 3 hours which occurred within 48 hours of administration of previous dose of Infanrix.
* 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 (including current thrombocytopenia), 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 was demonstrated.

Primary outcomes:
measure: Geometric Mean Concentrations (GMCs) for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Geometric Mean Concentrations (GMCs) for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Geometric Mean Titers (GMTs) for Anti-poliovirus Types 1, 2 and 3 Antibodies in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Number of Subjects With Booster Response Against Diphtheria Toxoid (D) and Tetanus Toxoid (T) Antigens in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Number of Subjects With Booster Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Number of Subjects With Circumferential Swelling at the Injection Site
timeFrame: Within 4 days (Day 0-3) after vaccination
Secondary outcomes:
measure: Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Antigens in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Number of Seroprotected Subjects Against Poliovirus Types 1, 2 and 3 Antigens in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Number of Seropositive Subjects Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Number of Subjects With Anti-D and Anti-T Antibody Concentrations Greater Than or Equal to (≥) 1 IU/mL
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Number of Subjects With Booster Response for Poliovirus Types 1, 2 and 3 Antigens in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Geometric Mean Titers (GMTs) for Serum Haemagglutination-inhibition (HI) Anti-H1N1, Anti-H3N2 and Anti-B Antibodies in a Subset of Subjects
timeFrame: At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination)
measure: Number of Seroconverted Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects
timeFrame: At Month 1 (i.e. one month after vaccination)
measure: Number of Seroprotected Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects
timeFrame: At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 4-day (Day 0-3) post-vaccination period
measure: Number of Subjects With Any and Grade 3 Increase in the Mid-upper Arm Circumference at the Injection Site
timeFrame: During the 4-day (Day 0-3) post-vaccination period
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 4-day (Day 0-3) post-vaccination period
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Specific to M-M-R II Vaccination
timeFrame: During the 15-day (Day 0-14) post-vaccination period
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within 31 days (Days 0-30) post-vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (from Day 0 through 6 months [minimum 182 days post-vaccination])
measure: Number of Subjects With Onset of Chronic Illness(es) and AE(s) Leading to Emergency Room (ER) or to Physician Office Visits
timeFrame: During the extended safety follow-up phase (i.e. 5 months following the active phase [from Day 31 up to minimum 182 days post-vaccination])
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Antioch
country: United States
facility: GSK Investigational Site
state: California
city: Daly City
country: United States
facility: GSK Investigational Site
state: California
city: Fairfield
country: United States
facility: GSK Investigational Site
state: California
city: Fremont
country: United States
facility: GSK Investigational Site
state: California
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: Hayward
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Pleasanton
country: United States
facility: GSK Investigational Site
state: California
city: Redwood City
country: United States
facility: GSK Investigational Site
state: California
city: Richmond
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 Francisco
country: United States
facility: GSK Investigational Site
state: California
city: San Jose
country: United States
facility: GSK Investigational Site
state: California
city: San Ramon
country: United States
facility: GSK Investigational Site
state: California
city: Santa Clara
country: United States
facility: GSK Investigational Site
state: California
city: Santa Rosa
country: United States
facility: GSK Investigational Site
state: California
city: Vacaville
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
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Mechanicsville
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Black S, Friedland LR, Ensor K, Weston WM, Howe B, Klein NP. Diphtheria-tetanus-acellular pertussis and inactivated poliovirus vaccines given separately or combined for booster dosing at 4-6 years of age. Pediatr Infect Dis J. 2008 Apr;27(4):341-6. doi: 10.1097/INF.0b013e3181616180.
citation: Weston WM, Klein NP. Kinrix: a new combination DTaP-IPV vaccine for children aged 4-6 years. Expert Rev Vaccines. 2008 Nov;7(9):1309-20. doi: 10.1586/14760584.7.9.1309.