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

Tetanus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00148941
• Other study ID #: 213503/048
• Status: Completed
• Phase: Phase 3
• Start date: January 6, 2005
• Est. completion date: December 4, 2006

Study information

• Verified date: January 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 4209
• Est. completion date: December 4, 2006
• Est. primary completion date: November 1, 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 4 Years to 6 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acellular Pertussis
• Diphtheria
• Tetanus

Intervention

Biological:
• SB213503 lot 1
SB213503 lot 1 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.
• SB213503 lot 2
SB213503 lot 2 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.
• SB213503 lot 3
SB213503 lot 3 vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.
• Infanrix
Infanrix vaccine was administered as a single dose by intramuscular injection in the deltoid at Day 0.
• IPOL
IPOL vaccine was administered as a single dose by subcutaneous injection in the deltoid at Day 0.
• M-M-R II
M-M-R II vaccine was administered as a single dose by subcutaneous injection in the deltoid at Day 0.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Antioch	California
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Daly City	California
United States	GSK Investigational Site	Fairfield	California
United States	GSK Investigational Site	Fremont	California
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Hayward	California
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Mechanicsville	Virginia
United States	GSK Investigational Site	Oakland	California
United States	GSK Investigational Site	Pleasanton	California
United States	GSK Investigational Site	Redwood City	California
United States	GSK Investigational Site	Richmond	California
United States	GSK Investigational Site	Roseville	California
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	San Ramon	California
United States	GSK Investigational Site	Santa Clara	California
United States	GSK Investigational Site	Santa Rosa	California
United States	GSK Investigational Site	Vacaville	California
United States	GSK Investigational Site	Vallejo	California
United States	GSK Investigational Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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).	At Month 1 (i.e. one month after vaccination)
Secondary	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.	At Month 1 (i.e. one month after vaccination)
Secondary	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).	At Month 1 (i.e. one month after vaccination)
Secondary	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.	At Month 1 (i.e. one month after vaccination)
Secondary	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.	At Month 1 (i.e. one month after vaccination)
Secondary	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.	At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination)
Secondary	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.	At Month 1 (i.e. one month after vaccination)
Secondary	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.	At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination)
Secondary	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.	During the 4-day (Day 0-3) post-vaccination period
Secondary	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.	During the 4-day (Day 0-3) post-vaccination period
Secondary	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.	During the 4-day (Day 0-3) post-vaccination period
Secondary	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.	During the 15-day (Day 0-14) post-vaccination period
Secondary	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.	Within 31 days (Days 0-30) post-vaccination period
Secondary	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.	During the entire study period (from Day 0 through 6 months [minimum 182 days post-vaccination])
Secondary	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.	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])

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