Primary Vaccination Study With a Pneumococcal Conjugate Vaccine in Healthy Children 6 to 12wks of Age

Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A, Infanrix Hexa and Rotarix

The purpose of this study is to assess the immunogenicity in terms of antibody response and the safety/reactogenicity in terms of solicited and unsolicited symptoms and serious adverse events following primary vaccination of Mexican infants with pneumococcal conjugate vaccine GSK 1024850A co-administered with a diphtheria, tetanus, acellular pertussis (DTPa)-combined vaccine (Infanrix hexa) and rotavirus vaccine (Rotarix) in children during the first 6 months of age.

Study Overview

• Status: Completed
• Conditions: Streptococcus Pneumoniae Vaccines; Infections, Streptococcal
• Intervention / Treatment: Biological: Synflorix; Biological: Infanrix hexa; Biological: Rotarix

Detailed Description

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

• Study Type: Interventional
• Enrollment (Actual): 230
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico, Mexico, 14000
    • GSK Investigational Site
  • Mexico city, Mexico, 14000
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects between and including 6-12 weeks of age at the time of the first vaccination.
• Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
• Written informed consent obtained from the parent 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 36 to 42 weeks inclusive.

Exclusion Criteria:

• 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.
• Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting one month before each dose of vaccines and ending 7 days after dose 1 and dose 2 and one month after dose 3.
• 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.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
• A family history of congenital or hereditary immunodeficiency.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
• Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, rotavirus and/or Streptococcus pneumoniae; with the exception of vaccines where the first dose may be given at birth within the first two weeks of life according to national recommendations (e.g. Hepatitis B and BCG).
• History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b disease.
• Gastroenteritis within 7 days preceding the study vaccine administration (warrants deferral of the vaccination).
• Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal (GI) tract, intussusception (IS) or other medical condition determined to be serious by the investigator.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
• History of any neurological disorders or seizures.
• Major congenital defects or serious chronic illness.
• Acute disease at the time of enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synflorix Vaccine Group; Subjects receiving Synflorix vaccine co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine at 2-4-6 months of age, and co-administered with HRV (Rotarix) vaccine at 2-4 months of age.	Biological: Synflorix; Intramuscular injection, 3 doses.; Other Names: Pneumococcal conjugate vaccine GSK1024850A.; Biological: Infanrix hexa; Intramuscular injection, 3 doses.; Biological: Rotarix; Oral, 2 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Concentrations Against Pneumococcal Vaccine Serotypes	Concentrations were expressed as geometric mean concentration (GMC). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Antibody Concentrations Against Protein D	Concentrations were given as geometric mean concentration (GMC) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter.	One month after the administration of the 3rd vaccine dose i.e. Month 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opsonophagocytic Titer Against Pneumococcal Vaccine Serotypes	The results were presented as the geometric mean dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Number of Subjects With Anti-pneumococcal Vaccine Serotypes Antibody Concentrations Greater Than or Equal to 0.2 Microgram Per Milliliter	The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes	Antibody concentrations were expressed as Geometric Mean Concentrations against pneumococcal cross-reactive serotypes 6A and 19A.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Opsonophagocytic Titer Against Pneumococcal Cross-reactive Serotypes	The results were presented as the geometric mean dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cross-reactive pneumococcal serotypes assessed include 6A and 19A.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Number of Subjects Seropositive Against Vaccine Pneumococcal Serotypes	Seropositivity was defined as anti-pneumococcal antibody concentration greater than or equal to 0.05 microgram per milliliter. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Number of Subjects Seropositive for Opsonic Titer Against Vaccine Pneumococcal Serotypes	Seropositivity was defined as an opsonic titer greater than or equal to 8. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Number of Subjects Seropositive Against Cross-reactive Pneumococcal Serotypes	Seropositivity was defined as anti-pneumococcal antibody concentration greater than or equal to 0.05 microgram per milliliter. The cross-reactive pneumococcal serotypes assessed include 6A and 19A.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Number of Subjects Seropositive for Opsonic Titer Against Cross-reactive Pneumococcal Serotypes	Seropositivity was defined as anti-pneumococcal antibody opsonic titer greater than or equal to 8. The vaccine pneumococcal cross-reactive serotypes assessed include 6A and 19A.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Number of Subjects Seropositive for Anti-Protein D Antibodies	Seropositivity was defined as antibody concentration greater than or equal to 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter.	One month after the administration of the 3rd vaccine dose i.e. Month 5
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs)	Grade 3 redness and swelling was > 30 millimeter (mm) and grade 3 pain was subjects crying when limb was moved/spontaneously painful. Any was occurrence of any local symptom regardless of grade and whatever the number of injections.	Within 4 days following any vaccine dose
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs	Any fever was defined as axillary temperature ≥ 37.5 degree centigrade (°C), grade 3 fever was axillary temperature > 39.5°C. Grade 3 drowsiness, irritability, and loss of appetite was general symptom which prevented normal everyday activities. Grade 3 diarrhea was ≥ 6 looser than normal stools/day and Grade 3 vomiting was ≥ 3 episodes of vomiting/day. Related was solicited general symptom considered by the investigator to have a causal relationship to study vaccination.	Within 4 days following any vaccine dose
Number of Subjects Reporting Any Unsolicited AEs	Unsolicited AE covers any AE 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.	Within 31 days after any vaccine dose
Number of Subjects Reporting Any Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.	Up to Month 5

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Silfverdal SA, Coremans V, Francois N, Borys D, Cleerbout J. Safety profile of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Expert Rev Vaccines. 2017 Feb;16(2):109-121. doi: 10.1586/14760584.2016.1164044. Epub 2016 Sep 30.
• Ruiz-Palacios G et al. Immunogenicity, safety and reactogenicity of the new 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in Mexican infants. Abstract presented at the XIII Congreso Latinoamericano de Infectología Pediátrica (SLIPE). Guayaquil, Ecuador, 12-15 August 2009.
• Ruiz-Palacios GM, Guerrero ML, Hernandez-Delgado L, Lavalle-Villalobos A, Casas-Munoz A, Cervantes-Apolinar Y, Moreira M, Schuerman L. Immunogenicity, reactogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Mexican infants. Hum Vaccin. 2011 Nov;7(11):1137-45. doi: 10.4161/hv.7.11.17984. Epub 2011 Nov 1.
• Schuerman L et al. Population variability in antibody responses following pneumococcal conjugate vaccination: experience with the non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L et al. Population variability of opsonophagocytic activity following 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate (PHiD-CV) vaccination more limited than antibody responses. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2007
• Primary Completion (Actual): March 31, 2008
• Study Completion (Actual): March 31, 2008

Study Registration Dates

• First Submitted: June 20, 2007
• First Submitted That Met QC Criteria: June 20, 2007
• First Posted (Estimate): June 21, 2007

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: December 30, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal disease; Primary vaccination; Pneumococcal vaccine.
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 109661; 2015-001510-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below).
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below).
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 109661
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 109661
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 109661
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 109661
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 109661
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 109661
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register