Immune Response and Safety Comparison of 3 Lots of GSK Biologicals' DTaP-IPV Candidate Vaccine to DTaP + IPV Vaccines

NCT00148941 | Completed Phase 3 Results

• 1 other identifier: 213503/048
• Study Type: interventional
• Target: 4,209
• Locations: 1 country
• Sites: 24

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.

Conditions

Tetanus; Acellular Pertussis; Diphtheria

Outcome Measures

Primary Outcomes (6)

• Geometric Mean Concentrations (GMCs) for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies in a Subset of Subjects

  GMCs were measured by Enzyme-Linked Immunosorbent assay (ELISA), expressed in international units per milliliter (IU/mL).

  At Month 1 (i.e. one month after vaccination)

• 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

  GMCs were measured by Enzyme-Linked Immunosorbent assay (ELISA), expressed in ELISA units per milliliter (EL.U/mL).

  At Month 1 (i.e. one month after vaccination)

• Geometric Mean Titers (GMTs) for Anti-poliovirus Types 1, 2 and 3 Antibodies in a Subset of Subjects

  GMTs were measured by Neutralization assay and expressed in titers.

  At Month 1 (i.e. one month after vaccination)

• Number of Subjects With Booster Response Against Diphtheria Toxoid (D) and Tetanus Toxoid (T) Antigens in a Subset of Subjects

  Vaccine response defined as: For initially seronegative subjects \[pre-booster antibody concentration below (\<) cut-off of 0.1 international units per milliliter (IU/mL)\] with an increase of at least four times the cut-off one month after vaccination \[post-booster antibody concentration greater than or equal to (≥) 0.4 IU/mL\]. For initially seropositive subjects (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.

  At Month 1 (i.e. one month after vaccination)

• Number of Subjects With Booster Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens in a Subset of Subjects

  Vaccine response defined as: For initially seronegative subjects \[pre-booster antibody concentration below (\<) cut-off of 5 EL.U/mL\] with an increase of at least four times the cut-off one month after vaccination (post-booster antibody concentration ≥ 20 EL.U/mL). For initially seropositive subjects with pre-booster antibody concentration ≥ 5 EL.U/mL and \< 20 EL.U/mL with an increase of at least 4 times the pre-booster antibody concentration one month after vaccination. For initially seropositive subjects with pre-booster antibody concentration ≥ 20 EL.U/mL with an increase of at least 2 times the pre-booster antibody concentration one month after vaccination.

  At Month 1 (i.e. one month after vaccination)

• Number of Subjects With Circumferential Swelling at the Injection Site

  Swelling (at the SB213503 \& Infanrix injection sites) was categorized as an increase of \> or ≤ 30 mm in mid upper arm circumference compared to baseline measurement or with an increase in mid upper arm missing; extent of swelling \> or ≤ 50 % of upper arm length, or diameter of injection site missing.

  Within 4 days (Day 0-3) after vaccination

Secondary Outcomes (15)

• Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Antigens in a Subset of Subjects

  At Month 1 (i.e. one month after vaccination)

• Number of Seroprotected Subjects Against Poliovirus Types 1, 2 and 3 Antigens in a Subset of Subjects

  At Month 1 (i.e. one month after vaccination)

• Number of Seropositive Subjects Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens in a Subset of Subjects

  At Month 1 (i.e. one month after vaccination)

• Number of Subjects With Anti-D and Anti-T Antibody Concentrations Greater Than or Equal to (≥) 1 IU/mL

  At Month 1 (i.e. one month after vaccination)

• Number of Subjects With Booster Response for Poliovirus Types 1, 2 and 3 Antigens in a Subset of Subjects

  At Month 1 (i.e. one month after vaccination)

Study Arms (4)

SB213503 lot 1 + M-M-R Group

EXPERIMENTAL

Subjects aged 4 to 6 years received a dose of lot 1 of SB213503 vaccine and a dose of M-M-R II vaccine. SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.

Biological: SB213503 lot 1; Biological: M-M-R II

SB213503 lot 2 + M-M-R Group

EXPERIMENTAL

Subjects aged 4 to 6 years received a dose of lot 2 of SB213503 vaccine and a dose of M-M-R II vaccine. SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.

Biological: SB213503 lot 2; Biological: M-M-R II

SB213503 lot 3 + M-M-R Group

EXPERIMENTAL

Subjects aged 4 to 6 years received a dose of lot 3 of SB213503 vaccine and a dose of M-M-R II vaccine. SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.

Biological: SB213503 lot 3; Biological: M-M-R II

Infanrix + IPOL + M-M-R Group

ACTIVE COMPARATOR

Subjects aged 4 to 6 years received a dose of Infanrix and a dose of IPOL vaccines separately and a dose of M-M-R II vaccine. Infanrix was administered by deep intramuscular injection in the upper left deltoid. IPOL was administered subcutaneously in the lower right deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.

Biological: Infanrix; Biological: IPOL; Biological: M-M-R II

Interventions

SB213503 lot 1 BIOLOGICAL

SB213503 lot 1 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.

Also known as: GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 1 vaccine

SB213503 lot 1 + M-M-R Group

SB213503 lot 2 BIOLOGICAL

SB213503 lot 2 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.

Also known as: GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 2 vaccine

SB213503 lot 2 + M-M-R Group

SB213503 lot 3 BIOLOGICAL

SB213503 lot 3 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.

Also known as: GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 3 vaccine

SB213503 lot 3 + M-M-R Group

Infanrix BIOLOGICAL

Infanrix vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.

Also known as: GSK Biologicals combined diphteria, tetanus, acellular pertussis vaccine

Infanrix + IPOL + M-M-R Group

IPOL BIOLOGICAL

IPOL vaccine was administered as a single dose by subcutaneous injection in the deltoid at Day 0.

Also known as: Aventis Pasteur inactivated poliovirus vaccine

Infanrix + IPOL + M-M-R Group

M-M-R II BIOLOGICAL

M-M-R II vaccine was administered as a single dose by subcutaneous injection in the deltoid at Day 0.

Also known as: Merck and Company licensed combined measles-mumps-rubella vaccine

Infanrix + IPOL + M-M-R Group; SB213503 lot 1 + M-M-R Group; SB213503 lot 2 + M-M-R Group; SB213503 lot 3 + M-M-R Group

Eligibility Criteria

• Age: 4 Years - 6 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (24)

GSK Investigational Site

Little Rock, Arkansas, 72205, United States

Location

GSK Investigational Site

Antioch, California, 94509, United States

Location

GSK Investigational Site

Daly City, California, 94015, United States

Location

GSK Investigational Site

Fairfield, California, 94533, United States

Location

GSK Investigational Site

Fremont, California, 94538, United States

Location

GSK Investigational Site

Fresno, California, 93726, United States

Location

GSK Investigational Site

Hayward, California, 94545, United States

Location

GSK Investigational Site

Oakland, California, 94611, United States

Location

GSK Investigational Site

Pleasanton, California, 94588, United States

Location

GSK Investigational Site

Redwood City, California, 94063, United States

Location

GSK Investigational Site

Richmond, California, 94801, United States

Location

GSK Investigational Site

Roseville, California, 95661, United States

Location

GSK Investigational Site

Sacramento, California, 95823, United States

Location

GSK Investigational Site

Sacramento, California, 95825, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

San Jose, California, 95119, United States

Location

GSK Investigational Site

San Ramon, California, 94583, United States

Location

GSK Investigational Site

Santa Clara, California, 95051, United States

Location

GSK Investigational Site

Santa Rosa, California, 95403, United States

Location

GSK Investigational Site

Vacaville, California, 95688, United States

Location

GSK Investigational Site

Vallejo, California, 94589, United States

Location

GSK Investigational Site

Walnut Creek, California, 94596, United States

Location

GSK Investigational Site

Columbus, Ohio, 43214, United States

Location

GSK Investigational Site

Mechanicsville, Virginia, 23111, United States

Location

Related Publications (2)

• 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.

  PMID: 18316985 BACKGROUND

• 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.

  PMID: 18980534 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Tetanus; Diphtheria

Interventions

Tetanus Toxoid; Diphtheria-Tetanus-acellular Pertussis Vaccines; Measles-Mumps-Rubella Vaccine

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Corynebacterium Infections; Actinomycetales Infections

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures; Pertussis Vaccine; Bacterial Vaccines; Diphtheria Toxoid; Vaccines, Combined; Vaccines, Acellular; Vaccines, Subunit; Measles Vaccine; Viral Vaccines; Mumps Vaccine; Rubella Vaccine

Limitations and Caveats

None reported.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study was conducted in an open manner except for the consistency lots of SB213503 vaccine that were double-blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2005
• First Posted: September 8, 2005
• Study Start: January 6, 2005
• Primary Completion: November 1, 2006
• Study Completion: December 4, 2006
• Last Updated: February 5, 2020
• Results First Posted: February 5, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (24)