TetanusPhase 3NCT00148941

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

A Phase 3 study testing SB213503 lot 1, SB213503 lot 2 and SB213503 lot 3 in people with Tetanus and Acellular Pertussis, run by GlaxoSmithKline at 24 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 4 to 6 yearsHealthy volunteers can take part
Conditions the study is for: Tetanus, Acellular Pertussis, Diphtheria
What is being tested?: SB213503 lot 1, SB213503 lot 2 and SB213503 lot 3
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4,209 participants
Where: 24 sitesUnited States
Study dates: 6 Jan 2005to 4 Dec 2006
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 4 to 6 years
All sexes
Healthy volunteers accepted
Child

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

24 sites in 1 country.

City, postcode or hospital

24 sites in 1 country

United States24 sites

GSK Investigational Site
Antioch, California, 94509
GSK Investigational Site
Columbus, Ohio, 43214
GSK Investigational Site
Daly City, California, 94015
GSK Investigational Site
Fairfield, California, 94533
GSK Investigational Site
Fremont, California, 94538
GSK Investigational Site
Fresno, California, 93726
GSK Investigational Site
Hayward, California, 94545
GSK Investigational Site
Little Rock, Arkansas, 72205
GSK Investigational Site
Mechanicsville, Virginia, 23111
GSK Investigational Site
Oakland, California, 94611
GSK Investigational Site
Pleasanton, California, 94588
GSK Investigational Site
Redwood City, California, 94063
GSK Investigational Site
Richmond, California, 94801
GSK Investigational Site
Roseville, California, 95661
GSK Investigational Site
Sacramento, California, 95823
GSK Investigational Site
Sacramento, California, 95825
GSK Investigational Site
San Francisco, California, 94115
GSK Investigational Site
San Jose, California, 95119
GSK Investigational Site
San Ramon, California, 94583
GSK Investigational Site
Santa Clara, California, 95051
GSK Investigational Site
Santa Rosa, California, 95403
GSK Investigational Site
Vacaville, California, 95688
GSK Investigational Site
Vallejo, California, 94589
GSK Investigational Site
Walnut Creek, California, 94596

Other trials in United States

About this study

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

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.

Read the 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).

Conditions: Tetanus, Acellular Pertussis, Diphtheria
Being tested: SB213503 lot 1, SB213503 lot 2, SB213503 lot 3, Infanrix, IPOL
Medical subject headings: Tetanus, Diphtheria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SB213503 lot 1Biological
Also called GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 1 vaccine
SB213503 lot 1 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.
SB213503 lot 2Biological
Also called GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 2 vaccine
SB213503 lot 2 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.
SB213503 lot 3Biological
Also called GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 3 vaccine
SB213503 lot 3 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.
InfanrixBiological
Also called GSK Biologicals combined diphteria, tetanus, acellular pertussis vaccine
Infanrix vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.
IPOLBiological
Also called Aventis Pasteur inactivated poliovirus vaccine
IPOL vaccine was administered as a single dose by subcutaneous injection in the deltoid at Day 0.
M-M-R IIBiological
Also called Merck and Company licensed combined measles-mumps-rubella vaccine
M-M-R II vaccine was administered as a single dose by subcutaneous injection in the deltoid at Day 0.

Study groups in NCT00148941
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Infanrix; Biological: IPOL; Biological: M-M-R II

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
A seroprotected subject is defined as a vaccinated subject with anti-D and anti-T antibody concentration greater than or equal to (≥) 0.1 international units per milliliter (IU/mL).
Measured: 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
A seroprotected subject is defined as a vaccinated subject with anti-poliovirus types 1, 2 and 3 antibody titers greater than or equal to 1:8.
Measured: 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
A seropositive subject was defined as a vaccinated subject with anti-PT, anti-FHA and anti-PRN antibody concentrations greater than or equal to (≥) 5 ELISA units per milliliter (EL.U/mL).
Measured: 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
The number of subjects with anti-D and anti-T antibody concentrations greater than or equal to (≥) 1 IU/mL is reported.
Measured: 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
Vaccine response defined as: For initially seronegative subjects (pre-booster antibody titer below cut-off of 1:8), an antibody titer ≥ 1:32 at one month after vaccination. For initially seropositive subjects (pre-booster antibody titer ≥1:8), an increase at least four times the pre-booster antibody titer at one month after vaccination.
Measured: At Month 1 (i.e. one month after vaccination)
Geometric Mean Titers (GMTs) for Serum Haemagglutination-inhibition (HI) Anti-H1N1, Anti-H3N2 and Anti-B Antibodies in a Subset of Subjects
GMTs were measured by hemagglutination inhibition assay and expressed in titers.
Measured: At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination)
Number of Seroconverted Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects
Seroconversion was defined as a post-vaccination haemagglutination-inhibition (HI) titer of ≥ 1:40 in an initially HI antibody seronegative subject (pre-vaccination HI titer < 1:10), or a ≥ 4 fold rise in HI titer in an initially HI antibody seropositive subject (pre-vaccination HI titer ≥ 1:10) The 3 flu strains assessed were H1N1, H3N2, and B.
Measured: At Month 1 (i.e. one month after vaccination)
Number of Seroprotected Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects
A seroprotected subject is defined as a vaccinated subject with anti-H1N1, anti-H3N2, and anti-B antibody titers greater than or equal to (≥) 1:40.
Measured: At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness, and swelling (at the SB213503 \& Infanrix vaccination sites). Any = any symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activities. Grade 3 redness/swelling = redness/swelling spreading up to or beyond 50 mm diameter.
Measured: During the 4-day (Day 0-3) post-vaccination period
Number of Subjects With Any and Grade 3 Increase in the Mid-upper Arm Circumference at the Injection Site
Assessed specific symptom was increase in mid upper arm circumference (at the SB213503 \& Infanrix injection sites). Any = any symptom regardless of intensity grade. Grade 3 increase in mid upper arm circumference = mid upper arm circumference greater than 30 mm.
Measured: During the 4-day (Day 0-3) post-vaccination period
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were drowsiness, fever (orally) [≥ 37.5 degrees Celsius (°C)] and loss of appetite. Any = any solicited general symptom irrespective of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = considered by the investigator to be related to the vaccine. Grade 3 fever = fever >39°C.
Measured: During the 4-day (Day 0-3) post-vaccination period
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Specific to M-M-R II Vaccination
Solicited general symptoms specific to M-M-R II vaccination were fever [≥ 37.5 degrees Celsius (°C)], rash/exanthem, parotid/salivary gland swelling, and suspected signs of meningism including febrile convulsions . Any = any symptom regardless of intensity grade. Grade 3 = symptom that prevented normal everyday activity. Related = considered by the investigator to be related to the vaccine. Grade 3 fever = fever >39°C.
Measured: During the 15-day (Day 0-14) post-vaccination period
Number of Subjects With Any Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Measured: Within 31 days (Days 0-30) post-vaccination period
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) that were assessed included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
Measured: During the entire study period (from Day 0 through 6 months [minimum 182 days post-vaccination])
Number of Subjects With Onset of Chronic Illness(es) and AE(s) Leading to Emergency Room (ER) or to Physician Office Visits
Among assessed chronic illness(es) were: autoimmune disorders, asthma, type I diabetes, and allergies. AEs leading to emergency room (ER) visits or to physician office visits that were not related to well-child care, vaccination, injury or common acute illnesses such as upper respiratory tract infection, otitis media, pharyngitis, and gastroenteritis.
Measured: 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])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Jan 20054 Dec 2006

First posted8 Sep 2005 (estimated)
Study start6 Jan 2005
Primary completion1 Nov 2006
Study completion4 Dec 2006

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for TetanusStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 4,209 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00148941
Sponsor's protocol ID: 213503/048
Status last verified: Jan 2020
First submitted: 7 Sep 2005
Last updated: 5 Feb 2020
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: Yes: IPD is available via the Clinical Study Data Request site (click on the link provided below)

Publications

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.
PubMed 18316985
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.
PubMed 18980534

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00148941
Acronym / sponsor ID: 213503/048
Conditions: Tetanus, Acellular Pertussis, Diphtheria
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 4,209 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 6 Jan 2005 (actual)
Primary completion: 1 Nov 2006 (actual)
Study completion: 4 Dec 2006 (actual)
First posted: 8 Sep 2005 (estimated)
Results: Posted 5 Feb 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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).

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
SB213503 lot 1 + M-M-R Group	Experimental	Biological: SB213503 lot 1, Biological: M-M-R IISubjects 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.
SB213503 lot 2 + M-M-R Group	Experimental	Biological: SB213503 lot 2, Biological: M-M-R IISubjects 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.
SB213503 lot 3 + M-M-R Group	Experimental	Biological: SB213503 lot 3, Biological: M-M-R IISubjects 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.
Infanrix + IPOL + M-M-R Group	Active comparator	Biological: Infanrix, Biological: IPOL, Biological: M-M-R IISubjects 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.

Who may qualify

Ages: 4 to 6 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (21 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SB213503 lot 1Also: GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 1 vaccineSB213503 lot 1 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.	Biological	SB213503 lot 1 + M-M-R Group
SB213503 lot 2Also: GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 2 vaccineSB213503 lot 2 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.	Biological	SB213503 lot 2 + M-M-R Group
SB213503 lot 3Also: GSK Biologicals combined diphteria, tetanus, acellular pertussis and inactivated poliovirus lot 3 vaccineSB213503 lot 3 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.	Biological	SB213503 lot 3 + M-M-R Group
InfanrixAlso: GSK Biologicals combined diphteria, tetanus, acellular pertussis vaccineInfanrix vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.	Biological	Infanrix + IPOL + M-M-R Group
IPOLAlso: Aventis Pasteur inactivated poliovirus vaccineIPOL vaccine was administered as a single dose by subcutaneous injection in the deltoid at Day 0.	Biological	Infanrix + IPOL + M-M-R Group
M-M-R IIAlso: Merck and Company licensed combined measles-mumps-rubella vaccineM-M-R II vaccine was administered as a single dose by subcutaneous injection in the deltoid at Day 0.	Biological	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

Primary outcome

Geometric Mean Concentrations (GMCs) for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies in a Subset of Subjects
Time frame: At Month 1 (i.e. one month after vaccination)
GMCs were measured by Enzyme-Linked Immunosorbent assay (ELISA), expressed in international units per milliliter (IU/mL).
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
Time frame: At Month 1 (i.e. one month after vaccination)
GMCs were measured by Enzyme-Linked Immunosorbent assay (ELISA), expressed in ELISA units per milliliter (EL.U/mL).
Geometric Mean Titers (GMTs) for Anti-poliovirus Types 1, 2 and 3 Antibodies in a Subset of Subjects
Time frame: At Month 1 (i.e. one month after vaccination)
GMTs were measured by Neutralization assay and expressed in titers.
Number of Subjects With Booster Response Against Diphtheria Toxoid (D) and Tetanus Toxoid (T) Antigens in a Subset of Subjects
Time frame: At Month 1 (i.e. one month after vaccination)
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.
Number of Subjects With Booster Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens in a Subset of Subjects
Time frame: At Month 1 (i.e. one month after vaccination)
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.
Number of Subjects With Circumferential Swelling at the Injection Site
Time frame: Within 4 days (Day 0-3) after vaccination
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.

15 secondary outcomes

Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Antigens in a Subset of Subjects
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At Month 1 (i.e. one month after vaccination)
Geometric Mean Titers (GMTs) for Serum Haemagglutination-inhibition (HI) Anti-H1N1, Anti-H3N2 and Anti-B Antibodies in a Subset of Subjects
Time frame: At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination)
Number of Seroconverted Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects
Time frame: At Month 1 (i.e. one month after vaccination)
Number of Seroprotected Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects
Time frame: At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 4-day (Day 0-3) post-vaccination period
Number of Subjects With Any and Grade 3 Increase in the Mid-upper Arm Circumference at the Injection Site
Time frame: During the 4-day (Day 0-3) post-vaccination period
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 4-day (Day 0-3) post-vaccination period
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Specific to M-M-R II Vaccination
Time frame: During the 15-day (Day 0-14) post-vaccination period
Number of Subjects With Any Unsolicited Adverse Events (AEs)
Time frame: Within 31 days (Days 0-30) post-vaccination period
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: During the entire study period (from Day 0 through 6 months [minimum 182 days post-vaccination])
Number of Subjects With Onset of Chronic Illness(es) and AE(s) Leading to Emergency Room (ER) or to Physician Office Visits
Time frame: 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])

Results and safety

Results posted to the registry on 5 Feb 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SB213503 Lot 1 + M-M-R Group	1,053	1,035
SB213503 Lot 2 + M-M-R Group	1,051	1,027
SB213503 Lot 3 + M-M-R Group	1,052	1,032
Infanrix + IPOL + M-M-R Group	1,053	1,029

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

Time frame: At Month 1 (i.e. one month after vaccination). Geometric mean (95% Confidence Interval). Unit: IU/mL

Measure	SB213503 Lot 1 + M-M-R Group n = 284	SB213503 Lot 2 + M-M-R Group n = 283	SB213503 Lot 3 + M-M-R Group n = 284	Infanrix + IPOL + M-M-R Group n = 261
Anti-D	16.704 (15.198 to 18.360)	18.658 (17.045 to 20.424)	18.437 (16.771 to 20.269)	18.112 (16.443 to 19.949)
Anti-T	9.693 (8.843 to 10.624)	9.974 (9.120 to 10.908)	11.300 (10.264 to 12.441)	11.235 (10.275 to 12.284)

SB213503 Lot 1 + M-M-R Group vs SB213503 Lot 2 + M-M-R Group: GMC ratio: 0.970 (95% CI 0.871 to 1.080), ANCOVA
SB213503 Lot 1 + M-M-R Group vs SB213503 Lot 3 + M-M-R Group: GMC ratio: 0.961 (95% CI 0.863 to 1.070), ANCOVA
SB213503 Lot 2 + M-M-R Group vs SB213503 Lot 3 + M-M-R Group: GMC ratio: 0.991 (95% CI 0.890 to 1.103), ANCOVA

Population analysed: The anaylsis was performed on a subset of subjects (first 1340 enrolled subjects who agreed to participate in the subset) belonging to the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects who received study vaccines according to protocol and for whom immunogenicity data were available for the analyzed antigen.

Primary outcome: 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

Time frame: At Month 1 (i.e. one month after vaccination). Geometric mean (95% Confidence Interval). Unit: EL.U/mL

Measure	SB213503 Lot 1 + M-M-R Group n = 285	SB213503 Lot 2 + M-M-R Group n = 281	SB213503 Lot 3 + M-M-R Group n = 285	Infanrix + IPOL + M-M-R Group n = 261
Anti-PT	66.9 (61.1 to 73.3)	74.1 (66.6 to 82.4)	71.4 (64.7 to 78.6)	80.4 (72.4 to 89.1)
Anti-FHA	809.1 (740.5 to 884.2)	918.8 (840.0 to 1005.0)	869.2 (795.2 to 950.2)	939.7 (858.3 to 1028.8)
Anti-PRN	617.4 (549.2 to 694.0)	584.7 (519.7 to 657.9)	594.2 (526.6 to 670.4)	593.8 (525.7 to 670.7)

SB213503 Lot 1 + M-M-R Group vs SB213503 Lot 2 + M-M-R Group: GMC ratio: 0.938 (95% CI 0.828 to 1.063), ANCOVA
SB213503 Lot 1 + M-M-R Group vs SB213503 Lot 3 + M-M-R Group: GMC ratio: 0.963 (95% CI 0.850 to 1.091), ANCOVA
SB213503 Lot 2 + M-M-R Group vs SB213503 Lot 3 + M-M-R Group: GMC ratio: 1.026 (95% CI 0.906 to 1.162), ANCOVA

Population analysed: The anaylsis was performed on a subset of subjects (first 1340 enrolled subjects who agreed to participate in the subset) belonging to the ATP cohort for immunogenicity, which included all evaluable subjects who received study vaccines according to protocol and for whom immunogenicity data were available for the analyzed antigen.

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

Time frame: At Month 1 (i.e. one month after vaccination). Geometric mean (95% Confidence Interval). Unit: Titers

Measure	SB213503 Lot 1 + M-M-R Group n = 276	SB213503 Lot 2 + M-M-R Group n = 274	SB213503 Lot 3 + M-M-R Group n = 276	Infanrix + IPOL + M-M-R Group n = 252
Anti-poliovirus 1	2095.0 (1852.1 to 2369.8)	2103.1 (1863.4 to 2373.5)	2129.2 (1889.2 to 2399.7)	1683.1 (1444.7 to 1960.9)
Anti-poliovirus 2	2345.4 (2104.8 to 2613.5)	2132.9 (1888.0 to 2409.5)	2326.6 (2074.5 to 2609.3)	1802.0 (1566.3 to 2073.2)
Anti-poliovirus 3	3683.5 (3283.4 to 4132.3)	3400.7 (3023.2 to 3825.4)	3603.8 (3185.1 to 4077.5)	3367.8 (2923.3 to 3879.8)

SB213503 Lot 1 + M-M-R Group vs SB213503 Lot 2 + M-M-R Group: GMT ratio: 0.994 (95% CI 0.836 to 1.181), ANCOVA
SB213503 Lot 1 + M-M-R Group vs SB213503 Lot 3 + M-M-R Group: GMT ratio: 0.987 (95% CI 0.831 to 1.172), ANCOVA
SB213503 Lot 2 + M-M-R Group vs SB213503 Lot 3 + M-M-R Group: GMT ratio: 0.993 (95% CI 0.836 to 1.180), ANCOVA

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

Time frame: At Month 1 (i.e. one month after vaccination). Count of participants. Unit: Participants

Measure	SB213503 Lot 1 + M-M-R Group n = 280	SB213503 Lot 2 + M-M-R Group n = 283	SB213503 Lot 3 + M-M-R Group n = 282	Infanrix + IPOL + M-M-R Group n = 261
Anti-D, Total	279	280	281	260
Anti-T, Total	266	273	277	245

SB213503 Lot 1 + M-M-R Group vs SB213503 Lot 2 + M-M-R Group vs SB213503 Lot 3 + M-M-R Group vs Infanrix + IPOL + M-M-R Group: Difference between groups: 0.47 (95% CI -0.98 to 1.21)
SB213503 Lot 1 + M-M-R Group vs SB213503 Lot 2 + M-M-R Group vs SB213503 Lot 3 + M-M-R Group vs Infanrix + IPOL + M-M-R Group: Difference between groups: -2.81 (95% CI -6.55 to -0.09)

Population analysed: The analysis was performed on a subset of subjects (first 1340 enrolled subjects who agreed to participate in the subset) belonging to the ATP cohort for immunogenicity, which included all evaluable subjects who received study vaccines according to protocol and for whom immunogenicity data were available for the analyzed antigen.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited symptoms: during the 4-day (Days 0-3) post-vaccination period; MMR II specific solicited symptoms: during the 15-day (Days 0-14) post-vaccination period; Unsolicited AEs: during the 31-day (Days 0-30) post-vaccination period; SAEs: during the entire study period (from Day 0 through 6 months [minimum 182 days post-vaccination]).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SB213503 Lot 1 + M-M-R Group	4 of 1,053 (0.4%)	797 of 1,053 (75.7%)	0 of 1,053
SB213503 Lot 2 + M-M-R Group	7 of 1,051 (0.7%)	783 of 1,051 (74.5%)	0 of 1,051
SB213503 Lot 3 + M-M-R Group	1 of 1,052 (0.1%)	814 of 1,052 (77.4%)	0 of 1,052
Infanrix + IPOL + M-M-R Group	4 of 1,053 (0.4%)	804 of 1,053 (76.4%)	0 of 1,053

Limitations and caveats (from the sponsor): None reported.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18316985Black 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.
Background: PubMed 18980534Weston 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.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. IPD is available via the Clinical Study Data Request site (click on the link provided below)

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

24 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing SB213503 lot 1, SB213503 lot 2 and SB213503 lot 3 in people with Tetanus and Acellular Pertussis, run by GlaxoSmithKline at 24 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Geometric Mean Concentrations (GMCs) for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies in a Subset of Subjects (time frame: At Month 1 (i.e. one month after vaccination)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00148941, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.