Clinical trial NCT01616459: Immunogenicity and Safety of Two Formulations of GSK Biologicals' Pneumococcal Vaccine (2830929A and 2830930A) When Administered in Healthy Infants
Official title: Immunogenicity and Safety Study of Two Formulations of GlaxoSmithKline (GSK) Biologicals' Pneumococcal Vaccine (2830929A and 2830930A) When Administered in Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Streptococcal
Keywords: Streptococcus pneumoniae
Haemophilus influenzae
Pneumococcal vaccine
Infants
Safety
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-06-11
Enrollment: 953
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 assess the immunogenicity, reactogenicity and safety of two formulations of GSK Biologicals' pneumococcal vaccine (2830929A and 2830930A) administered as 3-dose primary vaccination during the first 6 months of life followed by a booster dose in the second year of life. To comply with the routine infant immunisation program, the licensed GSK Biologicals DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine will be co-administered in infants with the pneumococcal study vaccines.

Detailed description: The purpose of this study is to assess the immunogenicity of the two formulations of GSK Biologicals' pneumococcal vaccine 2830929A (11-valent vaccine or 11Pn vaccine) and 2830930A (12-valent vaccine or 12Pn vaccine), when administered as 3-dose primary vaccination during the first 6 months of life followed by a booster dose in the second year of life, when compared to immune responses to the licensed vaccines Synflorix™ and Prevnar 13™, and to assess the reactogenicity and safety of these two same investigational formulations when administered according to this schedule. To comply with the routine infant immunisation program, the licensed GSK Biologicals DTPa-HBV-IPV/Hib (Infanrix hexa™) vaccine will be co-administered in infants with the pneumococcal study vaccines.

Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LARs) can and will comply with the requirements of the protocol.
* A male or female between, and including 6 to 12 weeks (42-90 days) of age at the time of the first vaccination. In addition, the first pneumococcal and DTPa-HBV-IPV/Hib vaccination should be given in accordance with the official national recommendations for the immunisation schedule of infants.
* Written informed consent obtained from the parents/LAR(s) of the subject.
* Healthy subjects 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 other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
* Planned administration/administration of a vaccine containing diphtheria toxoid, tetanus toxoid (except MenC-TT in Spain) or CRM197 and not foreseen by the study protocol during any time of the study period, or of any other vaccines not foreseen by the protocol in the period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s), with the following exceptions:

  * Licensed influenza vaccines are always allowed, even if concomitantly administered with the study vaccines.
  * Licensed rotavirus vaccines are allowed if administered at least 7 days before or after each dose of study of vaccines.
  * Licensed MenC-TT vaccine is allowed in Spain and should be concomitantly administered with the study vaccine at around 2, 4 and 12-15 months of age.
  * In case an emergency mass vaccination for an unforeseen public health threat (e.g. a pandemic) is organised by the public health authorities, outside the routine immunization program, that vaccine can be administered at any time during the study period provided it is licensed and used according to its Summary of Product Characteristics or Prescribing Information and according to the local governmental 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 .
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* 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, including Kawasaki's syndrome.
* History of any neurological disorders or seizures, including conditions such as hypotensive-hyporesponsive episodes, encephalopathy and any convulsions (afebrile and febrile).
* Acute disease and/or fever at the time of enrolment.
* Administration of immunoglobulins and/or any blood products since birth or planned administration during study period.
* Previous vaccination against diphtheria, tetanus, pertussis, polio, H. influenzae type b.
* Previous vaccination against S. pneumoniae.
* History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, H. influenzae type b disease.
* Any medical condition which might interfere with the assessment of the study objectives in the opinion of the investigator.

Primary outcomes:
measure: Antibody Concentrations Against Pneumococcal Serotypes During the Primary Phase of the Study
timeFrame: At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
measure: Percentage (%) of Subjects (Synflorix and 11Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Pneumococcal Serotypes
timeFrame: 1 month post-dose 3 (primary phase)
measure: Percentage (%) of Subjects (Prevnar13 and 11Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Anti-19A Pneumococcal Serotype
timeFrame: 1 month post-dose 3 (primary phase)
measure: Percentage (%) of Subjects (Synflorix and 12Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Pneumococcal Serotypes
timeFrame: 1 month post-dose 3 (primary phase)
measure: Percentage (%) of Subjects (Prevnar13 and 12Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Anti-6A and 19A Pneumococcal Serotypes
timeFrame: 1 month post-dose 3 (primary phase)
Secondary outcomes:
measure: Antibody Concentrations Against Pneumococcal Serotypes During the Booster Phase of the Study
timeFrame: At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Primary Phase of the Study
timeFrame: At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Booster Phase of the Study
timeFrame: At study Month 11, e.g.: at one month post booster vaccination with pneumococcal vaccine
measure: Concentrations of Antibodies Against Protein D (Anti-PD) During the Primary Phase of the Study
timeFrame: At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
measure: Concentrations of Antibodies Against Protein D (Anti-PD) During the Booster Phase of the Study
timeFrame: At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Primary Phase
timeFrame: Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D).
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Booster Phase of the Study
timeFrame: Within the 4-day (Days 0-3) period after booster vaccination
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, During the Primary Phase of the Study
timeFrame: Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D).
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, During the Booster Phase of the Study
timeFrame: Within the 4-day (Days 0-3) period after booster vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) During the Primary Phase of the Study
timeFrame: Within the 31-day (Days 0-30) period post primary vaccination, across doses
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) During the Booster Phase of the Study
timeFrame: Within the 31-day (Days 0-30) period post booster vaccination
measure: Number of Subjects With Any Serious Adverse Events (SAEs)During the Primary Phase of the Study
timeFrame: From Month 0 to Month 3
measure: Number of Subjects With Any Serious Adverse Events (SAEs) During the Entire Duration of the Study
timeFrame: From Day 0 to Month 11
measure: Antibody Concentrations Against Pneumococcal Serotype 6A During the Booster Phase of the Study
timeFrame: At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 19A During the Primary Phase of the Study
timeFrame: At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 19A During the Booster Phase of the Study
timeFrame: At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine
measure: Antibody Concentrations Against Pneumococcal Serotype 6C During the Primary Phase of the Study.
timeFrame: At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
measure: Antibody Concentrations Against Pneumococcal Serotype 6C During the Booster Phase of the Study.
timeFrame: At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C During the Primary Phase of the Study
timeFrame: At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
measure: Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C During the Booster Phase of the Study
timeFrame: At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine
Other outcomes:
Locations:
city: Benesov
country: Czechia
facility: GSK Investigational Site
city: Decin
country: Czechia
facility: GSK Investigational Site
city: Domazlice
country: Czechia
facility: GSK Investigational Site
city: Jindrichuv Hradec
country: Czechia
facility: GSK Investigational Site
city: Kladno
country: Czechia
facility: GSK Investigational Site
city: Liberec
country: Czechia
facility: GSK Investigational Site
city: Lipnik nad Becvou
country: Czechia
facility: GSK Investigational Site
city: Nachod
country: Czechia
facility: GSK Investigational Site
city: Ostrava - Poruba
country: Czechia
facility: GSK Investigational Site
city: Ostrov
country: Czechia
facility: GSK Investigational Site
city: Pardubice
country: Czechia
facility: GSK Investigational Site
city: Plzen
country: Czechia
facility: GSK Investigational Site
city: Praha 6
country: Czechia
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: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Berchtesgaden
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: Olching
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Detmold
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Kleve-Materborn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Loehne
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Frankenthal
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Trier
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Wanzleben
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Flensburg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Debica
country: Poland
facility: GSK Investigational Site
city: Olesnica
country: Poland
facility: GSK Investigational Site
city: Siemianowice Slaskie
country: Poland
facility: GSK Investigational Site
city: Torun
country: Poland
facility: GSK Investigational Site
city: Trzebnica
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Almería
country: Spain
facility: GSK Investigational Site
city: Antequera/Málaga
country: Spain
facility: GSK Investigational Site
city: Burgos
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
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Carmona Martinez A, Prymula R, Miranda Valdivieso M, Otero Reigada MDC, Merino Arribas JM, Brzostek J, Szenborn L, Ruzkova R, Horn MR, Jackowska T, Centeno-Malfaz F, Traskine M, Dobbelaere K, Borys D. Immunogenicity and safety of 11- and 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccines (11vPHiD-CV, 12vPHiD-CV) in infants: Results from a phase II, randomised, multicentre study. Vaccine. 2019 Jan 3;37(1):176-186. doi: 10.1016/j.vaccine.2018.07.023. Epub 2018 Jul 24.