Study in Children to Evaluate the Immunogenicity and Safety of 4 Formulations of GSK Bio MenACWY-TT Conjugate Vaccine

A Phase II, Open (Partially Double-blind), Randomized, Controlled Dose-range Study to Evaluate the Immunogenicity, Reactogenicity and Safety of Investigational Vaccination Regimens Versus MENINGITEC™ or MENCEVAX™ ACWY When Given as One Dose to Children Aged 12 to 14 Months and 3 to 5 Years Old

The purpose of this study is to evaluate the immunogenicity, safety and reactogenicity of one dose of four different formulations of the MenACWY conjugate vaccine when given to healthy children aged 12 14 months and 3 5 years. The selection of the best formulation will be based on data obtained up to one month after the vaccine dose. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, September 2007.

Study Overview

• Status: Completed
• Conditions: Infections, Meningococcal
• Intervention / Treatment: Biological: Conjugated meningococcal ACWY-TT (vaccine); Biological: DTPa/Hib containing vaccine; Biological: Mencevax ACWY; Biological: Meningitec

Detailed Description

The study will enrol subjects of 12 to 14 months of age and subjects of 3 to 5 years of age. Meningitec™ or Mencevax™ ACWY vaccine will serve as active control. The study will be conducted in two stages: The primary vaccination phase (Study Stage 1) of the study will include all subjects; the second (booster/persistence) phase of the study (Study Stage 2) will include subjects in the active control groups and in the group which was primed with the selected MenACWY formulation.

• Study Type: Interventional
• Enrollment (Actual): 508
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Guessing, Austria, A-7540
    • GSK Investigational Site
  • Neufeld/Leitha, Austria, A 2491
    • GSK Investigational Site
  • Salzburg, Austria, A-5020
    • GSK Investigational Site
  • Villach, Austria, A-9500
    • GSK Investigational Site
  • Wels, Austria, A-4600
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10315
    • GSK Investigational Site
  • Berlin, Germany, 10967
    • GSK Investigational Site
  • Berlin, Germany, 13055
    • GSK Investigational Site
  • Berlin, Germany, 12627
    • GSK Investigational Site
  • Berlin, Germany, 12679
    • GSK Investigational Site
  • Berlin, Germany, 14197
    • GSK Investigational Site
  • Berlin, Germany, 13355
    • GSK Investigational Site
  • Berlin, Germany, 10999
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Bietigheim/Bissingen, Baden-Wuerttemberg, Germany, 74321
      • GSK Investigational Site
    • Bretten, Baden-Wuerttemberg, Germany, 75015
      • GSK Investigational Site
    • Eppelheim, Baden-Wuerttemberg, Germany, 69214
      • GSK Investigational Site
    • Ludwigsburg, Baden-Wuerttemberg, Germany, 71634
      • GSK Investigational Site
    • Mannheim, Baden-Wuerttemberg, Germany, 68309
      • GSK Investigational Site
    • Oberstenfeld, Baden-Wuerttemberg, Germany, 71720
      • GSK Investigational Site
  • Bayern
    • Bindlach, Bayern, Germany, 95463
      • GSK Investigational Site
    • Bobingen, Bayern, Germany, 86399
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 81735
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 81675
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 80939
      • GSK Investigational Site
    • Noerdlingen, Bayern, Germany, 86720
      • GSK Investigational Site
    • Nuernberg, Bayern, Germany, 90473
      • GSK Investigational Site
    • Olching, Bayern, Germany, 82140
      • GSK Investigational Site
    • Tegernsee, Bayern, Germany, 83684
      • GSK Investigational Site
    • Tutzing, Bayern, Germany, 82327
      • GSK Investigational Site
    • Weilheim, Bayern, Germany, 82362
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Bodenheim, Rheinland-Pfalz, Germany, 55294
      • GSK Investigational Site
    • Gerolstein, Rheinland-Pfalz, Germany, 54568
      • GSK Investigational Site
    • Ludwigshafen, Rheinland-Pfalz, Germany, 67059
      • GSK Investigational Site
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • GSK Investigational Site
    • Trier, Rheinland-Pfalz, Germany, 54294
      • GSK Investigational Site
    • Worms, Rheinland-Pfalz, Germany, 67547
      • GSK Investigational Site
  • Sachsen
    • Doebeln, Sachsen, Germany, 04720
      • GSK Investigational Site
    • Dresden, Sachsen, Germany, 01169
      • GSK Investigational Site
    • Leipzig, Sachsen, Germany, 04178
      • GSK Investigational Site
    • Stollberg, Sachsen, Germany, 09366
      • GSK Investigational Site
  • Thueringen
    • Lobenstein, Thueringen, Germany, 07356
      • GSK Investigational Site
    • Weimar, Thueringen, Germany, 99425
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• 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 14 months or 3 and 5 years of age at the time of the first vaccination
• 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
• Previously completed routine childhood vaccinations to the best of his/her parents'/guardians' knowledge. For pertussis vaccination, the children aged 12-14 months should have been vaccinated with an acellular pertussis vaccine.

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.
• 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 one month of the first dose of vaccine and up to one month after administration of each study vaccine dose with the exception of oral polio vaccine.
• Previous vaccination against meningococcal serogroup A, C, W-135 or Y disease.
• Administration of a H. influenzae type b, diphtheria or tetanus vaccine within 3 months before the first dose of vaccine.
• For subjects aged 12-14 months at enrolment, a DTPa/Hib containing booster vaccination, in the second year of life: these booster vaccines will be given at Visit 2.
• History of meningococcal serogroup A, C, W-135 or Y disease.
• Known exposure to meningococcal serogroup A, C, W-135 or Y disease within the previous year.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• A family history of congenital or hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Major congenital defects or serious chronic illness.
• History of any neurologic disorders or seizures.
• 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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Subjects of 12-14 months of age or 3-5 years of age who will receive formulation A	Biological: Conjugated meningococcal ACWY-TT (vaccine); One intramuscular dose during the primary vaccination; Biological: DTPa/Hib containing vaccine; One intramuscular dose during the primary vaccination study in subjects of 12-14 months of age
Experimental: Group B; Subjects of 12-14 months of age or 3-5 years of age who will receive formulation B	Biological: Conjugated meningococcal ACWY-TT (vaccine); One intramuscular dose during the primary vaccination; Biological: DTPa/Hib containing vaccine; One intramuscular dose during the primary vaccination study in subjects of 12-14 months of age
Experimental: Group C; Subjects of 12-14 months of age or 3-5 years of age who will receive formulation C	Biological: Conjugated meningococcal ACWY-TT (vaccine); One intramuscular dose during the primary vaccination; Biological: DTPa/Hib containing vaccine; One intramuscular dose during the primary vaccination study in subjects of 12-14 months of age; Biological: Mencevax ACWY; One subcutaneous dose during the primary vaccination study in subjects of 3-5 years of age (group E) and subcutaneous administration of 1/5 dose during the booster vaccination study in subjects of 12-14 months of age (group C, group E)
Experimental: Group D; Subjects of 12-14 months of age or 3-5 years of age who will receive formulation D	Biological: Conjugated meningococcal ACWY-TT (vaccine); One intramuscular dose during the primary vaccination; Biological: DTPa/Hib containing vaccine; One intramuscular dose during the primary vaccination study in subjects of 12-14 months of age
Active Comparator: Group E; Subjects of 12-14 months of age who will receive Meningitec and subjects of 3-5 years of age who will receive Mencevax ACWY.	Biological: DTPa/Hib containing vaccine; One intramuscular dose during the primary vaccination study in subjects of 12-14 months of age; Biological: Mencevax ACWY; One subcutaneous dose during the primary vaccination study in subjects of 3-5 years of age (group E) and subcutaneous administration of 1/5 dose during the booster vaccination study in subjects of 12-14 months of age (group C, group E); Biological: Meningitec; One intramuscular dose during the primary vaccination study in subjects of 12-14 months of age

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of meningococcal rSBA responders, in all subjects	One month after the first vaccine dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Meningococcal rSBA titres	Prior to & 1 month after the 1st dose in all subjects and 15 months after priming in all subjects of groups C and E and one month after administration of the Mencevax ACWY booster dose in all subjects who received the booster dose
Anti-meningococcal polysaccharide concentrations	Prior to & 1 month after the 1st dose in all subjects and 15 months after priming in all subjects of groups C and E and one month after administration of the Mencevax ACWY booster dose in all subjects who received the booster dose
Anti-tetanus toxoid seropositivity and antibody concentrations	Prior to and one month after administration of the first vaccine dose, in all subjects
Meningococcal hSBA titers	Prior to & 1 month after the 1st dose and 15 months after priming in all subjects of groups C and E and one month after administration of the Mencevax ACWY booster dose in all subjects who received the booster dose
Occurrence of local and general solicited adverse events	During the 8-day follow-up period following the administration of each vaccine dose.
Occurrence of unsolicited adverse events	During the 31-day follow-up period following the administration of each vaccine dose.
Occurrence of any serious adverse events	Throughout the study

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Knuf M, Kieninger-Baum D, Habermehl P, Muttonen P, Maurer H, Vink P, Poolman J, Boutriau D. A dose-range study assessing immunogenicity and safety of one dose of a new candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine administered in the second year of life and in young children. Vaccine. 2010 Jan 8;28(3):744-53. doi: 10.1016/j.vaccine.2009.10.064. Epub 2009 Nov 1.
• Knuf M, Baine Y, Bianco V, Boutriau D, Miller JM. Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children. Hum Vaccin Immunother. 2012 Jul;8(7):866-72. doi: 10.4161/hv.20229. Epub 2012 Apr 9.
• Knuf M et al. Antibody persistence and immune memory 15 months after meningococcal tetravalent tetanus toxoid conjugate (ACWY-TT) vaccine in toddlers and 3-5 year-olds. Abstract presented at the 27th annual ESPID meeting, Brussels, Belgium, 9-13 June 2009.
• Prieler et al. Immunogenicity of 1 dose of a candidate meningococcal tetravalent tetanus toxoid conjugate (MenACWY-TT) vaccine in 12-14 month and 3-5 year olds. Abstract presented at the 47th Annual Meeting of Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Chicago, IL, 17-20 September 2007.
• Prieler et al. Immunogenicity of 1-dose of a new meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine in children 12-14 months and 3-5 years old. Abstract presented at the 9th Meeting of The European Monitoring Group on Meningococci (EMGM). Rome, Italy, 30 May-1 June 2007.

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: July 1, 2005
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: August 4, 2005
• First Submitted That Met QC Criteria: August 4, 2005
• First Posted (Estimate): August 5, 2005

Study Record Updates

• Last Update Posted (Estimate): October 7, 2016
• Last Update Submitted That Met QC Criteria: October 6, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Reactogenicity; Conjugate vaccine; Meningococcal vaccine; Dose selection
• 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
• Other Study ID Numbers: 104703 (Primary study); 104704 (Other Identifier: GSK)

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. Clinical Study Report
   Information identifier: 104703 (Primary study)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 104703 (Primary study)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 104703 (Primary study)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 104703 (Primary study)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 104703 (Primary study)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 104703 are summarised with study 104704 on the GSK Clinical Study Register.
6. Dataset Specification
   Information identifier: 104703 (Primary study)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register