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

Non-inferiority of a Commercial Lot of the Pneumococcal Vaccine GSK1024850A Compared to a Clinical Lot.

The purpose of the present study is to demonstrate that the changes in the manufacturing process for the commercial lot of the pneumococcal conjugate vaccine GSK1024850A have no clinical impact and that the immune responses are non-inferior to the immune responses induced by the clinical lot. The study will be conducted in Singapore and Malaysia.

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots); Biological: Infanrix hexa; Biological: Infanrix-IPV/Hib; Biological: Rotarix

• Study Type: Interventional
• Enrollment (Actual): 466
• Phase: Phase 3

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • GSK Investigational Site
  • Seremban, Negeri Sembilan, Malaysia, 70300
    • GSK Investigational Site
• Singapore
  • Singapore, Singapore, 119074
    • GSK Investigational Site
  • Singapore, Singapore, 229899
    • GSK Investigational Site
  • Singapore, Singapore, 149547
    • 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 parent(s)/guardian(s) can and will comply with the requirements of the protocol.
• Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child/ward.
• Free of any known or suspected 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.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period.
• Concurrently participating in another clinical study, at any time during the study period.
• 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 (with the exception of hepatitis B immunoglobulins at birth).
• Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae (with the exception of vaccines where the first dose can be given within the first two weeks of life).
• Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of vaccine and ending 7 days after Dose 1 and Dose 2 and 30 days after Dose 3.
• History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, H. influenzae type b and rotavirus disease.
• 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.
• Gastroenteritis within 7 days preceding the study vaccine administration.
• Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract, intussusception or other medical condition determined to be serious by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Synflorix Clinical Lot & Infanrix Group; Subjects received 3 doses of the clinical lot of Synflorix TM (GSK1024850A) intramuscularly in the right thigh at 2-3-5 months of age (= study month 0, 1, 3) co-administered with a DTPa-combined vaccine (Infanrix hexa TM (at 2, 3 and 5 months of age in Malaysia or 2 and 5 months of age in Singapore) or Infanrix-IPV/Hib TM (at 3 months of age in Singapore)) intramuscularly in the left thigh and Rotarix TM orally at 2-3 months of age (= study month 0, 1).	Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots); Intramuscular injection, 3 doses; Biological: Infanrix hexa; Intramuscular injection, 3 doses in Malaysia and 2 doses in Singapore; Other Names: DTPa-combined vaccine; Biological: Infanrix-IPV/Hib; Intramuscular injection, only for Visit 2 in Singapore; Other Names: DTPa-combined vaccine; Biological: Rotarix; Oral, 2 doses; Other Names: HRV vaccine
EXPERIMENTAL: Synflorix Commercial Lot Infanrix Group; Subjects received 3 doses of the commercial lot of Synflorix TM (GSK1024850A) intramuscularly in the lright thigh at 2-3-5 months of age (= study month 0, 1, 3) co-administered with a DTPa-combined vaccine (Infanrix hexa TM (at 2, 3 or 5 months of age in Malaysia or 2 and 5 months in Singapore) or Infanrix-IPV/Hib TM (at 3 months of age in Singapore)) intramuscularly in the left thigh and Rotarix TM orally at 2-3 months of age (= study month 0, 1).	Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots); Intramuscular injection, 3 doses; Biological: Infanrix hexa; Intramuscular injection, 3 doses in Malaysia and 2 doses in Singapore; Other Names: DTPa-combined vaccine; Biological: Infanrix-IPV/Hib; Intramuscular injection, only for Visit 2 in Singapore; Other Names: DTPa-combined vaccine; Biological: Rotarix; Oral, 2 doses; Other Names: HRV vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine	Concentrations are given as Geometric Mean Concentrations (GMCs) in microgram per milliliter (μg/mL). Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.	One month after primary immunization (month 4)
Concentration of Antibody Against Protein D (PD)	Concentration was expressed as GMC in GSK's 22F enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL).	One month after primary immunization (month 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL	Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.	One month after primary immunization (month 4)
Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL	Anti-pneumococcal cross-reactive serotypes were 6A and 19A.	One month after primary immunization (month 4)
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes	Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8.	One month after primary immunization (month 4)
Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes	Cross-reactive pneumococcal serotypes were 6A and 19A. Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8.	One month after primary immunization (month 4)
Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes	Opsonophagocytic titers were expressed as GMTs. Cross-reactive pneumococcal serotypes included 6A and 19A.	One month after primary immunization (month 4)
Poliovirus Types 1, 2 and 3 Titers	Titers were given as Geometric Mean Titers (GMTs).	One month after primary immunization (month 4)
Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT)	Concentrations were defined as GMCs in international units per milliter (IU/mL)	One month after primary immunization (month 4)
Concentration of Antibody Against Hepatitis B Surface Antigen (HBs) by Enzyme Linked ImmunoSorbent Assay (ELISA).	Concentration was given as GMC in milli international units per milliliter (mIU/mL). As a decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table shows results following partial or complete reanalysis.	One month after primary immunization (month 4)
Concentration of Antibody Against Rotavirus Immunoglobulin A (IgA)	Concentration was expressed as GMC in units per milliliter (U/mL).	3 months after primary immunization (month 4)
Occurrence of Serious Adverse Events	SAEs assessed include medical occurrences that result in death, is 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.	Following vaccination and throughout the entire study period (Month 0 to Month 4)
Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes	Titers are presented as Geometric Mean Titers (GMTs). Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.	One month after primary immunization (month 4)
Number of Subjects With Solicited Local and General Symptoms.	Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were drowsiness, fever, irritability, loss of appetite, diarrhoea and vomiting.	Within 4 days (day 0-3) after vaccination
Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN)	Concentrations are expressed as GMCs in EL.U/mL.	One month after primary immunization (month 4)
Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP)	Concentrain was expressed as GMC in µg/mL.	One month after primary immunization (month 4)
Occurrence of Unsolicited Adverse Events	An AE is 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.	Within 31 days (day 0-30) after vaccination

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Lim FS, Koh MT, Tan KK, Chan PC, Chong CY, Shung Yehudi YW, Teoh YL, Shafi F, Hezareh M, Swinnen K, Borys D. A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia. BMC Infect Dis. 2014 Oct 2;14:530. doi: 10.1186/1471-2334-14-530.

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: January 5, 2009
• Primary Completion (ACTUAL): November 2, 2009
• Study Completion (ACTUAL): November 2, 2009

Study Registration Dates

• First Submitted: December 11, 2008
• First Submitted That Met QC Criteria: December 11, 2008
• First Posted (ESTIMATE): December 15, 2008

Study Record Updates

• Last Update Posted (ACTUAL): August 17, 2018
• Last Update Submitted That Met QC Criteria: July 11, 2018
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal vaccine; Pneumococcal disease; Primary vaccination
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 111654

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 111654
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 111654
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 111654
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 111654
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 111654
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 111654
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: 111654
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register