Immune Response and Safety Comparison of 3 Lots of GSK Biologicals' DTaP-IPV Candidate Vaccine to DTaP + IPV Vaccines
- Conditions
- DiphtheriaTetanusAcellular Pertussis
- Interventions
- Biological: SB213503 lot 3Biological: InfanrixBiological: SB213503 lot 1Biological: SB213503 lot 2Biological: IPOLBiological: M-M-R II
- Registration Number
- NCT00148941
- Lead Sponsor
- GlaxoSmithKline
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4209
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SB213503 lot 3 + M-M-R Group SB213503 lot 3 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. Infanrix + IPOL + M-M-R Group Infanrix 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. SB213503 lot 1 + M-M-R Group SB213503 lot 1 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. Infanrix + IPOL + M-M-R Group M-M-R II 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. SB213503 lot 3 + M-M-R Group M-M-R II 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. Infanrix + IPOL + M-M-R Group IPOL 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. SB213503 lot 1 + M-M-R Group M-M-R II 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. SB213503 lot 2 + M-M-R Group M-M-R II 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. SB213503 lot 2 + M-M-R Group SB213503 lot 2 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.
- Primary Outcome Measures
Name Time Method Geometric Mean Concentrations (GMCs) for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies in a Subset of Subjects 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).
Number of Subjects With Booster Response 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) 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.
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 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 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 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 Circumferential Swelling at the Injection Site 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.
- Secondary Outcome Measures
Name Time Method Number of Subjects With Any Unsolicited Adverse Events (AEs) Within 31 days (Days 0-30) post-vaccination period 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.
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) 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).
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) 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.
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) 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).
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) 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.
Number of Seroprotected Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination) 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.
Number of Subjects With Any and Grade 3 Increase in the Mid-upper Arm Circumference at the Injection Site During the 4-day (Day 0-3) post-vaccination period 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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Specific to M-M-R II Vaccination During the 15-day (Day 0-14) post-vaccination period 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.
Number of Subjects With Serious Adverse Events (SAEs) During the entire study period (from Day 0 through 6 months [minimum 182 days post-vaccination]) 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.
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) The number of subjects with anti-D and anti-T antibody concentrations greater than or equal to (≥) 1 IU/mL is reported.
Geometric Mean Titers (GMTs) for Serum Haemagglutination-inhibition (HI) Anti-H1N1, Anti-H3N2 and Anti-B Antibodies in a Subset of Subjects At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination) GMTs were measured by hemagglutination inhibition assay and expressed in titers.
Number of Seroconverted Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects At Month 1 (i.e. one month after vaccination) 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.
Number of Subjects With Onset of Chronic Illness(es) and AE(s) Leading to Emergency Room (ER) or to Physician Office Visits 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]) 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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms During the 4-day (Day 0-3) post-vaccination period 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.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the 4-day (Day 0-3) post-vaccination period 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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Mechanicsville, Virginia, United States