Co-administration of Meningococcal Vaccine GSK134612 and Pneumococcal Vaccine GSK1024850A vs Individual Administration

Immunogenicity & Safety Study of GSK Biologicals' Meningococcal Vaccine GSK134612 When Co-administered With GSK Biologicals' Pneumococcal Vaccine GSK1024850A in Healthy 12-23-month-old Children Previously Primed With GSK1024850A

The purpose of this study is to demonstrate, in 12-23 months old subjects, the non-inferiority of meningococcal vaccine GSK134612 and pneumococcal vaccine GSK1024850A when co-administered, compared to each vaccine administered individually.

Study Overview

• Status: Completed
• Conditions: Infections, Meningococcal
• Intervention / Treatment: Biological: Meningococcal vaccine GSK134612; Biological: Pneumococcal vaccine GSK1024850A

Detailed Description

Multi-center study with 3 parallel groups. One group will receive 2 vaccines injections at the same visit (pneumococcal+ meningococcal), one group will receive a pneumococcal vaccine followed one month later by a meningococcal vaccine, and the last group will receive the meningococcal vaccine followed one month later by the pneumococcal vaccine.

All subjects will have one blood sample taken before vaccination and one blood sample taken one month after each vaccination (i.e. the first group will have 2 blood samples taken, and the other two groups will have 3 blood sample taken)

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico, Mexico, 14000
    • GSK Investigational Site
  • Mexico city, Mexico, 14000
    • GSK Investigational Site
• Taiwan
  • Taipei, Taiwan, 100
    • GSK Investigational Site
  • Taipei, Taiwan, 105
    • GSK Investigational Site
  • Taoyuan Hsien, Taiwan
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
• A male or female between, and including, 12 and 23 months of age at the time of the first booster vaccination, who previously participated in study 109661 conducted in Mexico or in study 109861 conducted in Taiwan and who received 3 doses of the GSK1024850A vaccine.
• Written informed consent obtained from the parent or guardian of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.

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 study vaccine(s), or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine(s) and 30 days after the last dose of vaccine(s).
• 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 with a meningococcal vaccine.
• Previous administration of a fourth dose of a pneumococcal vaccine
• Previous vaccination with tetanus toxoid within the last month (including also tetanus toxoid given as part of Hib-TT conjugate vaccine).
• History of meningococcal or pneumococcal invasive disease.
• History of reactions or allergic disease likely to be exacerbated by any component of the vaccines.
• Hypersensitivity reaction due to previous vaccination with GSK1024850A vaccine.
• History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or progressive neurological disease.
• 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).
• A family history of congenital or hereditary immunodeficiency, unless the child has previously been documented, through laboratory testing, to have normal immune function.
• Major congenital defects or serious chronic illness.
• Acute disease at the time of enrolment.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Meningococcal vaccine GSK134612 co-administered with pneumococcal vaccine GSK1024850A.	Biological: Meningococcal vaccine GSK134612; Single dose intramuscular injection.; Biological: Pneumococcal vaccine GSK1024850A; Single dose intramuscular injection.
Active Comparator: Group B; Pneumococcal vaccine GSK1024850A followed one month later by meningococcal vaccine GSK134612.	Biological: Meningococcal vaccine GSK134612; Single dose intramuscular injection.; Biological: Pneumococcal vaccine GSK1024850A; Single dose intramuscular injection.
Active Comparator: Group C; Meningococcal vaccine GSK134612 followed one month later by pneumococcal vaccine GSK1024850A.	Biological: Meningococcal vaccine GSK134612; Single dose intramuscular injection.; Biological: Pneumococcal vaccine GSK1024850A; Single dose intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-pneumococcal Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (µg/mL). Anti-pneumococcal serotypes assessed were Anti-1, Anti-4, Anti-5, Anti-6B, Anti-7F, Anti-9V, Anti-14, Anti-18C, Anti-19F and Anti-23F via the 22F-inhibition Enzyme Linked Immunosorbent Assay (ELISA).	At Month 1
Number of Subjects With Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C , W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW -135 and rSBA-Men-Y) Antibody Titers Greater Than or Equal to (≥) the Cut-off Value	The cut-off value for the rSBA titers was greater than or equal to (≥) 1:8.	At Month 1
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-Men-Y Antibody Titers	Antibody titers are presented as geometric mean titers (GMTs) and are measured in titers.	At Month 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-pneumococcal Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (µg/mL). The pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) via 22F-inhibition ELISA. GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose.	Before vaccination (PRE) and at one month post dose 2 (Month 2)
Cross-reactive Anti-pneumococcal Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in µg/mL. The pneumococcal serotypes assessed were 6A and 19A (anti-6A and anti-19A) via the 22F-inhibition ELISA. GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose.	Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2)
Opsonophagocytic Titers Against Pneumococcal Serotypes	Opsonophagocytic titers are presented as geometric mean titers (GMTs). The pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPSONO-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). GMTs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose.	Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2)
Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes	Opsonophagocytic titers are presented as geometric mean titers (GMTs). The pneumococcal serotypes assessed were 6A and 19A (OPSONO-6A and OPSONO-19A). GMTs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose.	Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2)
Anti-protein D (Anti-PD) Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose.	Before vaccination (PRE), at one month post dose 1(Month 1) and at one month post dose 2 (Month 2)
rSBA-MenA, rSBA-MenC, rSBA-MenW -135 and rSBA-Men-Y Antibody Titers	Antibody titers are presented as geometric mean titers (GMTs) and measured in titers. GMTs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose.	Before vaccination (PRE) and at one month post dose 2 (Month 2)
Anti-meningococcal Polysaccharide (Anti-PS) Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (µg/mL). GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose.	Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2)
Anti-tetanus (Anti-T) Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). GMCs post Dose 2 are not presented for Nimenrix + Synflorix Group, as they received only one study vaccination dose.	Before vaccination (PRE), at one month post dose 1 (Month 1) and at one month post dose 2 (Month 2)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	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.	Within the 4-day (Days 0-3) post-vaccination period after each dose
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature [defined as rectally temperature equal to or above (≥) 38.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activities. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever higher than (>) 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination.	Within the 4-day (Days 0-3) post-vaccination period after each dose
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 (Day 0-30) post-vaccination period after each dose
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.	Throughout the entire study duration (Day 0-Month 7)
Number of Subjects Reporting Rash	Rash-like symptoms assessed were hives, idiopathic thrombocytopenic purpura, petechiae.	Throughout the entire study duration (Day 0-Month 7)
Number of Subjects With New Onset Chronic Illnesses (NOCIs)	NOCIs include autoimmune disorders, asthma, type I diabetes, allergies.	Throughout the entire study duration (Day 0-Month 7)
Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits	Among AEs prompting emergency room visits were: infections, injuries, skin diseases, gastrointestinal symptoms.	Throughout the entire study duration (Day 0-Month 7)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Huang LM et al. Immunogenicity and safety of PHiD-CV coadministered with a candidate meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in children previously primed with PHiD. Abstract presented at the 5th Asian Congress of Pediatric Infectious Diseases (ACPID). Taipei, Taiwan, 23-26 September 2010.
• Ruiz-Palacios GM, Huang LM, Lin TY, Hernandez L, Guerrero ML, Villalobos AL, Van der Wielen M, Moreira M, Fissette L, Borys D, Miller JM. Immunogenicity and safety of a booster dose of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine coadministered with the tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in toddlers: a randomized trial. Pediatr Infect Dis J. 2013 Jan;32(1):62-71. doi: 10.1097/INF.0b013e3182784143.

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: October 30, 2008
• Primary Completion (Actual): June 2, 2009
• Study Completion (Actual): November 2, 2009

Study Registration Dates

• First Submitted: September 23, 2008
• First Submitted That Met QC Criteria: September 23, 2008
• First Posted (Estimate): September 25, 2008

Study Record Updates

• Last Update Posted (Actual): May 9, 2018
• Last Update Submitted That Met QC Criteria: May 8, 2018
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal vaccine; Meningococcal vaccine; Routine infancy vaccination
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 111393

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. Dataset Specification
   Information identifier: 111393
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 111393
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 111393
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 111393
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 111393
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 111393
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 111393
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register