Clinical trial NCT01144663: Immunogenicity and Safety of Meningococcal Vaccine GSK 134612 Co-administered With Pneumococcal and DTPa-HBV-IPV/Hib Vaccines
Official title: Immunogenicity and Safety of GSK Biologicals' Meningococcal Vaccine (GSK 134612) When Co-administered With a Pneumococcal Conjugate Vaccine and Infanrix Hexa™ in Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Meningococcal
Meningococcal Vaccines
Keywords: Infants
conjugate vaccine
immunogenicity
meningococcal vaccine
non-inferiority
co-administration
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-06-15
Enrollment: 2095
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate immunogenicity and safety of meningococcal conjugate vaccine GSK134612 compared to the licensed vaccines MenC-CRM197 and MenC-TT in infants of 2 months of age. Pneumococcal conjugate vaccine and DTPa-HBV-IPV/Hib vaccines will be co-administered.

Detailed description: The study consists of a primary vaccination phase and a booster vaccination phase. The Protocol Posting has been updated due to protocol amendment 2.

Eligibility criteria: Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

* Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit).
* A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.
* Written informed consent obtained from the parent(s) or guardian of the subject.
* Free of obvious health problems as established by medical history and clinical examination before entering into the study.
* Born after a gestation period of at least 36 weeks.

Exclusion Criteria:

* Child in care.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Extended administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone \>= 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
* Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the first dose of vaccine(s) until 30 days after the last dose of vaccine(s) (i.e. booster dose), with the exception of rotavirus vaccine which can be administered at any time during the study, according to the national immunisation recommendations. MMR(V) vaccine, if recommended in national immunisation programs, can be given after the last blood sampling time point i.e. after Visit 6. Seasonal or pandemic influenza vaccine can be given at any time during the study, and according to the Summary of Product Characteristics and national recommendations.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis serogroups A, C, W-135 or Y with the exception of vaccines where the first dose may be given within the first two weeks of life according to the national recommendations (for example hepatitis B and BCG).
* History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease, pneumococcal and/or meningococcal disease.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* Family history of congenital or hereditary immunodeficiency.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
* Major congenital defects or serious chronic illness.
* History of any neurologic disorders or seizures (history of a single, simple febrile seizure is permitted).
* Acute disease and/or fever at the time of enrolment. (Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting, or ≥ 38.0°C (100.4°F) on rectal setting).

(Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator).

- Administration of immunoglobulins and/ or any blood products since birth or planned administration during the study period.

Primary outcomes:
measure: Percentage of Subjects With Serum Bactericidal Assay Using Baby Rabbit Complement Against Meningococcal Serogroups A, W-135 and Y (rSBA-MenA, rSBA-MenW-135 and rSBA-Y) Antibody Titers Greater Than or Equal to (≥) the Cut-off Value.
timeFrame: One month after the final primary vaccination at Month 3
measure: Number of Subjects With rSBA-MenC Antibody Titers ≥ the Cut-off Value
timeFrame: One month after the final primary vaccination at Month 3
Secondary outcomes:
measure: Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers Above Cut-off Values
timeFrame: Pre-primary vaccination at Month 0
measure: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers
timeFrame: Pre-primary vaccination at Month 0
measure: Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, rSBA-MenY Antibody Titers Above the Cut-off Values
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Number of Subjects With Serum Bactericidal Assay Using Human Complement Against Meningococcal Serogroups (hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY) Antibody Titers Above the Cut-off Values
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers Above the Cut-off Values
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Number of Subjects With Anti-pneumococcal Serotypes (Anti-P) Antibody Concentrations Above the Cut-off Values
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Anti-pneumococcal Serotypes Antibody Concentrations
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Number of Subjects With Anti-pneumococcal Serotypes Antibody Concentrations Above the Cut-off Values
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Anti-pneumococcal Serotypes Antibody Concentrations
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Number of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Concentrations ≥ the Cut-off Value
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Anti-D and Anti-T Antibody Concentrations
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ the Cut-off Value
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Anti-D and Anti-T Antibody Concentrations
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Concentrations ≥ the Cut-off Value
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations ≥ the Cut-off Value
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Values
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Anti-HBs Antibody Concentrations
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Number of Subjects With Anti-HBs Antibody Concentrations Above the Cut-off Values
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Anti-HBs Antibody Concentrations
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Number of Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Concentrations ≥ the Cut-off Values
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Anti-PRP Antibody Concentrations
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Number of Subjects With Anti-PRP Antibody Concentrations Above the Cut-off Values
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Anti-PRP Antibody Concentrations
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Number of Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentrations ≥ the Cut-off Value
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Anti-polio Type 1, 2 and 3 Antibody Titers
timeFrame: Pre-primary vaccination at Month 0 and one month after final primary vaccination at Month 3
measure: Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Concentrations ≥ the Cut-off Value
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Anti-polio Type 1, 2 and 3 Antibody Titers
timeFrame: Pre-Booster dose at Month 10 and one month post-Booster dose at Month 11
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 8-day (Days 0-7) post-vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination
timeFrame: During the 8-day (Days 0-7) post-meningococcal vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Infanrix™ Hexa Vaccination
timeFrame: During the 8-day (Days 0-7) post-Infanrix hexa vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Synflorix Vaccination
timeFrame: During the 8-day (Days 0-7) post-Synflorix vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination
timeFrame: During the 8-day (Days 0-7) post-meningococcal booster vaccination period
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Infanrix™ Hexa Vaccination
timeFrame: During the 8-day (Days 0-7) post-Infanrix™ hexa booster vaccination period
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within 31-days (Days 0-30) post-each primary vaccination dose
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms Post-Synflorix™ Vaccination
timeFrame: During the 8-day (Days 0-7) post-Synflorix™ booster vaccination period
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 8-day (Days 0-7) post-vaccination period following each dose and across doses from Day 0 to Month 3 (Primary Vaccination)
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 8-day (Days 0-7) post-booster vaccination period
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within 31-days (Days 0-30) post-booster vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the entire study (from Day 0 to Month 16)
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Booster vaccination (Month 10) up to Extended Safety Follow-Up (ESFU) (Month 16)
measure: Number of Subjects With New Onset of Chronic Illnesses (NOCIs)
timeFrame: During 31-days (Days 0-30) post-each primary vaccination dose (Day 0 to Month 3) and from primary vaccination up to ESFU (Month 16)
measure: Number of Subjects With New Onset of Chronic Illnesses (NOCIs)
timeFrame: From Booster vaccination (Month 10 to Month 11) up to ESFU (Month 16)
Other outcomes:
Locations:
city: Haabneeme
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Kehl
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Schwaebisch-Hall
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Berchtesgaden
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bindlach
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Gilching
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Kirchheim
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Weilheim
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Baunatal-Grossenritte
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Eschwege
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Vellmar
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Detmold
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Kleve-Materborn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Porta Westfalica
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Solingen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Frankenthal
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Trier
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Worms
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Wanzleben
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Weissenfels
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Wurzen
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Flensburg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Lobenstein
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Almería
country: Spain
facility: GSK Investigational Site
city: Antequera/Málaga
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Blanes (Girona)
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Ciudad Real
country: Spain
facility: GSK Investigational Site
city: Manlleu
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valladolid
country: Spain
facility: GSK Investigational Site
city: Vic
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Merino Arribas JM, Carmona Martinez A, Horn M, Perez Porcuna XM, Otero Reigada MD, Mares Bermudez J, Centeno Malfaz F, Miranda M, Mendez M, Garcia Cabezas MA, Wittermann C, Bleckmann G, Fischbach T, Kolhe D, van der Wielen M, Baine Y. Safety and Immunogenicity of the Quadrivalent Meningococcal Serogroups A, C, W and Y Tetanus Toxoid Conjugate Vaccine Coadministered With Routine Childhood Vaccines in European Infants: An Open, Randomized Trial. Pediatr Infect Dis J. 2017 Apr;36(4):e98-e107. doi: 10.1097/INF.0000000000001484.
citation: Merino Arribas JM, Carmona Martinez A, Horn M, Perez Porcuna XM, Otero Reigada MDC, Mares Bermudez J, Centeno Malfaz F, Miranda M, Mendez M, Garcia Cabezas MA, Christoph W, Bleckmann G, Fischbach T, Kolhe D, Van der Wielen M, Baine Y. Immunogenicity and Reactogenicity of DTPa-HBV-IPV/Hib and PHiD-CV When Coadministered With MenACWY-TT in Infants: Results of an Open, Randomized Trial. Pediatr Infect Dis J. 2018 Jul;37(7):704-714. doi: 10.1097/INF.0000000000002061.