Clinical trial NCT01175083: Immunization of Children Between 8 Weeks and 2 Years of Age With GSK Pneumococcal Vaccine GSK1024850A
Official title: Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Pneumococcal Vaccine 1024850A When Administered to Children Between 8 Weeks and 2 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Keywords: Immunogenicity
Booster vaccination
Catch-up vaccination
Pneumococcal vaccine
Pneumococcal disease
Sickle cell disease
Safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-08-04
Enrollment: 300
Sex: ALL
Minimum age (years): 8
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of the study is to evaluate the immunogenicity, safety and reactogenicity of GSK Biologicals' pneumococcal conjugate vaccine GSK1024850A.

Children that are below 6 months at the time of enrolment will also receive the DTPw-HBV/Hib and OPV vaccines.

Detailed description: This protocol posting has been updated according to Protocol Amendment 2, September 2010. The impacted sections are arms and inclusion criteria.

Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
* A male or female between, and including:

  * 8 and 11 weeks of age at the time of the first vaccination for subjects in the \<6S and \<6NS groups or
  * 7 and 11 months at the time of the first vaccination for subjects in the 7-11S and 7-11NS groups or
  * 12 and 23 months at the time of first vaccination for subjects in the 12-23S and 12-23NS groups (Note the second dose should be administered at 23 Months of age at the latest to allow, if needed, compliance with the National Recommendations on administration of the 23-valent polysaccharide pneumococcal vaccine in children with SCD as of 24 months of age).
* Written informed consent, signed or thumb printed, obtained from the parent(s)/LAR(s) of the subject. Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by a witness.

Additional inclusion criteria for children with SCD (\<6S, 7-11S and 12-23S groups):

* Children with diagnosis of sickle cell disease \[homozygous sickle cell disease (hemoglobin SS disease), double heterozygous sickle hemoglobin C disease (hemoglobin SC disease) and the sickle ß-thalassemias\] and confirmed hemoglobin status by hemoglobin chromatography and electrophoresis (\<6S group) or electrophoresis (7-11S and 12-23S groups).
* Free of any other known or suspected health problems (as established by medical history and clinical examination before entering into the study), that would contraindicate the initiation of routine immunizations outside a clinical trial context

Additional inclusion criteria for healthy children (\<6NS, 7-11NS and 12-23NS groups):

* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Children with negative diagnosis of sickle cell disease and confirmed hemoglobin status by hemoglobin chromatography and/or electrophoresis.

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.
* Chronic 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 from 30 days before each dose of study vaccines and ending 30 days after. Locally recommended vaccines (recommended through the EPI program or through national immunization campaigns) for example inactivated influenza vaccine are always allowed, even if concomitantly administered with the study vaccines, but should be documented in the eCRF.
* 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 or planned vaccination during the study with any pneumococcal vacccine.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
* Major congenital malformations.
* History of any neurological disorders or seizures.
* Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
* Birth weight below 1500g.
* Serious chronic illness other than SCD.
* Acute disease and/or fever at the time of enrolment.

  * Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting, or ≥ 38.0°C on rectal setting. The preferred route for recording temperature in this study will be tympanic.
  * Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.

Additional exclusion criteria for children with SCD (\<6S, 7-11S and 12-23S groups):

• Any confirmed or suspected immunosuppressive or immunodeficient condition, (including human immunodeficiency virus (HIV) infection) other than SCD related conditions, based on medical history and physical examination (no laboratory testing required).

Additional exclusion criteria for healthy children (\<6 NS, 7-11NS and 12-23NS groups):

• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and physical examination (no laboratory testing required).

Primary outcomes:
measure: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines
timeFrame: One month after primary vaccination (Month 3)
measure: Concentrations of Antibodies Against Protein D (PD) for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines
timeFrame: One month after the primary vaccination (Month 3)
Secondary outcomes:
measure: Concentration of Antibodies Against Vaccine Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines
timeFrame: Prior to the primary vaccination (Month 0), prior to (Month 8) and one month after (Month 9) booster vaccination
measure: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose
timeFrame: Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
measure: Concentration of Antibodies Against Vaccine Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose
timeFrame: Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
measure: Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines
timeFrame: Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
measure: Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose
timeFrame: Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
measure: Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose
timeFrame: Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
measure: Concentration of Antibodies Against Protein D (PD) for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines
timeFrame: Prior to (Month 0) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
measure: Concentration of Antibodies Against Protein D (PD) for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose
timeFrame: Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
measure: Concentration of Antibodies Against Protein D (PD) for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose
timeFrame: Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
measure: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines
timeFrame: Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
measure: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose
timeFrame: Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
measure: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose
timeFrame: Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
measure: Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines
timeFrame: Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
measure: Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose
timeFrame: Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
measure: Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose
timeFrame: Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
measure: Concentration of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT) for Subjects Who Were Co-administered Tritanrix-HepB/Hib Vaccine
timeFrame: Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
measure: Concentrations of Antibodies Against Bordetella Pertussis (BPT) for Subjects Who Were Co-administered Tritanrix-HepB/Hib Vaccine
timeFrame: Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Primary Vaccination Phase
timeFrame: During the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Booster Vaccination Phase
timeFrame: During the 4-day (Days 0-3) post-booster vaccination period
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms During the Primary Vaccination Phase
timeFrame: During the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms During the Booster Vaccination Phase
timeFrame: During the 4-day (Days 0-3) post-booster vaccination period
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within the 31-day (Days 0-30) post-primary and post-booster vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period from Month 0 to Month 9
Other outcomes:
Locations:
city: Ouagadougou
country: Burkina Faso
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Sirima SB, Tiono A, Gansane Z, Siribie M, Zongo A, Ouedraogo A, Francois N, Strezova A, Dobbelaere K, Borys D. Immunogenicity and Safety of 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Administered to Children With Sickle Cell Disease Between 8 Weeks and 2 Years of Age: A Phase III, Open, Controlled Study. Pediatr Infect Dis J. 2017 May;36(5):e136-e150. doi: 10.1097/INF.0000000000001518.