Immunization of Children Between 8 Weeks and 2 Years of Age With GSK Pneumococcal Vaccine GSK1024850A

Infections, Streptococcal Clinical Trial

Official title:

Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Pneumococcal Vaccine 1024850A When Administered to Children Between 8 Weeks and 2 Years of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01175083
• Other study ID #: 114056
• Secondary ID: 2012-000254-64
• Status: Completed
• Phase: Phase 3
• Start date: June 1, 2011
• Est. completion date: May 23, 2013

Study information

• Verified date: February 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: May 23, 2013
• Est. primary completion date: January 17, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Weeks to 23 Months

Eligibility

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).

Related Conditions & MeSH terms

• Infections, Streptococcal
• Streptococcal Infections

Intervention

Biological:
• GSK1024850A (Synflorix)
2, 3 or 4 intramuscular injection
• Tritanrix-HepB/Hib
Intramuscular injection, 4 doses
• Polio Sabin
4 oral doses

Locations

Country	Name	City	State
Burkina Faso	GSK Investigational Site	Ouagadougou

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Burkina Faso, 

References & Publications (1)

Sirima SB, Tiono A, Gansané Z, Siribié M, Zongo A, Ouédraogo A, François 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines	Antibodies have been assessed against the following vaccine pneumococcal serotypes: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration greater than or equal to (=) 0.05 micrograms per milliliter (µg/mL). Antibody concentrations below than (<) 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	One month after primary vaccination (Month 3)
Primary	Concentrations of Antibodies Against Protein D (PD) for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines	Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration = 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	One month after the primary vaccination (Month 3)
Secondary	Concentration of Antibodies Against Vaccine Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines	Antibodies have been assessed against the following vaccine pneumococcal serotypes: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration = 0.05 micrograms per milliliter (µg/mL). Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to the primary vaccination (Month 0), prior to (Month 8) and one month after (Month 9) booster vaccination
Secondary	Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose	Antibodies have been assessed against the following vaccine pneumococcal serotypes: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration = 0.05 micrograms per milliliter (µg/mL). Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
Secondary	Concentration of Antibodies Against Vaccine Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose	Antibodies have been assessed against the following vaccine pneumococcal serotypes: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration = 0.05 micrograms per milliliter (µg/mL). Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
Secondary	Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines	Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A, -19A) were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration = 0.05 micrograms per milliliter (µg/mL). Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
Secondary	Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose	Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A, -19A) were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration = 0.05 micrograms per milliliter (µg/mL). Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
Secondary	Concentration of Antibodies Against Cross-reactive Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose	Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A, -19A) were measured by 22F enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration = 0.05 micrograms per milliliter (µg/mL). Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
Secondary	Concentration of Antibodies Against Protein D (PD) for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines	Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration = 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (Month 0) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
Secondary	Concentration of Antibodies Against Protein D (PD) for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose	Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration = 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
Secondary	Concentration of Antibodies Against Protein D (PD) for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose	Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration = 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
Secondary	Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines	Opsonophagocytic activity has been assessed against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) and presented as geometric mean titers (GMTs). The seropositivity cut-off for the assay was = 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
Secondary	Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose	Opsonophagocytic activity has been assessed against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) and presented as geometric mean titers (GMTs). The seropositivity cut-off for the assay was = 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
Secondary	Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose	Opsonophagocytic activity has been assessed against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) and presented as geometric mean titers (GMTs). The seropositivity cut-off for the assay was = 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
Secondary	Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes for Subjects Receiving Synflorix Vaccine Co-administered With Tritanrix-HepB/Hib and Polio Sabin Vaccines	Opsonophagocytic activity has been assessed for cross-reactive vaccine pneumococcal serotypes 6A and 19A (OPA-6A, OPA-19A) and presented as geometric mean titers (GMTs). The seropositivity cut-off for the assay was = 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
Secondary	Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Followed by a Booster Dose	Opsonophagocytic activity has been assessed for cross-reactive vaccine pneumococcal serotypes 6A and 19A (OPA-6A, OPA-19A) and presented as geometric mean titers (GMTs). The seropositivity cut-off for the assay was = 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	Prior to (Month 0) and one month after (Month 2) primary vaccination, prior to (Month 3) and one month after (Month 4) booster vaccination
Secondary	Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes for Subjects Who Received a Two-dose Primary Vaccination Without Any Booster Dose	Opsonophagocytic activity has been assessed for cross-reactive vaccine pneumococcal serotypes 6A and 19A (OPA-6A, OPA-19A) and presented as geometric mean titers (GMTs). The seropositivity cut-off for the assay was = 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	Prior to (Month 0) the first vaccine dose, prior to (Month 2) and one month after (Month 3) the second vaccine dose
Secondary	Concentration of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT) for Subjects Who Were Co-administered Tritanrix-HepB/Hib Vaccine	Anti-DT and anti-TT antibody concentrations are presented as geometric mean concentrations (GMCs) and expressed in international units per milliliter (IU/mL). Seroprotection status was defined as anti-DT or anti-TT antibody concentration = than 0.1 IU/mL.	Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
Secondary	Concentrations of Antibodies Against Bordetella Pertussis (BPT) for Subjects Who Were Co-administered Tritanrix-HepB/Hib Vaccine	Anti-BPT antibody concentrations are presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration = 15 EL.U/mL.	Prior to (Month 0) and one month after (Month 3) primary vaccination, prior to (Month 8) and one month after (Month 9) booster vaccination
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Primary Vaccination Phase	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.	During the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Booster Vaccination Phase	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.	During the 4-day (Days 0-3) post-booster vaccination period
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms During the Primary Vaccination Phase	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as rectal temperature equal to or above (=) 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 4-day (Days 0-3) post-primary vaccination period following each dose and across doses
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms During the Booster Vaccination Phase	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as rectal temperature equal to or above (=) 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 4-day (Days 0-3) post-booster 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 the 31-day (Days 0-30) post-primary and post-booster vaccination period
Secondary	Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the entire study period from Month 0 to Month 9

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