Primary Study to Demonstrate Non-inferiority and Immunogenicity of GSK Biologicals' Meningococcal Vaccine 134612

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00465816
First received: April 24, 2007
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

This study will demonstrate the non-inferiority of GSK Biologicals' meningococcal vaccine 134612 when given in an experimental co-administration versus vaccine 134612 alone and versus the experimental co-administration alone in healthy subjects aged 11 through 17 years. There will be 3 groups in this study.


Condition Intervention Phase
Meningococcal Serogroup A, C, W-135, Y Diseases
Biological: Nimenrix (Meningococcal vaccine 134612)
Biological: Twinrix
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Non-inferiority of GSK Biologicals' Meningococcal Vaccine 134612 Given Concomitantly With GSK Biologicals' Twinrix™ Versus 134612 Alone and Twinrix™ Alone in Healthy Subjects Aged 11 Through 17 Years.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Meningococcal Polysaccharide A Serum Bactericidal Antibodies/Assay, Using Baby Rabbit Complement for Assay (rSBA-MenA), rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers [ Time Frame: At 1 month after vaccination with Nimenrix vaccine (Month 1) ] [ Designated as safety issue: No ]
    The rSBA titers were expressed as geometric mean titers.

  • Number of Subjects Seroconverted for Hepatitis A [ Time Frame: At 1 month after the third dose of Twinrix vaccine (Month 7) ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a subject with anti-Hepatitis A virus (HAV) antibody concentration greater than or equal to 15 milli-International Units per Milliliter (mIU/mL) in previously seronegative subjects.

  • Number of Subjects Seroprotected for Hepatitis B [ Time Frame: At 1 month after the third dose of Twinrix vaccine (Month 7) ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a subject with anti-Hepatitis B surface antigen (HBs) antibody concentration greater than or equal to 10 milli-International Units per Milliliter (mIU/mL).


Secondary Outcome Measures:
  • Number of Subjects With a Vaccine Response to MenA, MenC, MenY and MenW-135 [ Time Frame: At 1 month after vaccination with Nimenrix vaccine (Month 1) ] [ Designated as safety issue: No ]
    Vaccine response is defined as an rSBA titer of at least 1:32 in subjects initially seronegative [rSBA titer below1:8] and as a 4-fold increase in titer in subjects initially seropositive [rSBA titre greater than or equal to 1:8].

  • Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers Above Predefined Cut-off Values [ Time Frame: Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) ] [ Designated as safety issue: No ]
    The cut-off values assessed were greater than or equal to (≥) 1:8 and ≥ 1:128.

  • Anti-PSA (Polysaccharide A), Anti-PSC (Polysaccharide C), Anti-PSW-135 (Polysaccharide W-135), and Anti-PSY (Polysaccharide Y) Antibody Concentrations [ Time Frame: Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) ] [ Designated as safety issue: No ]
    Concentrations were provided as Geometric Mean Concentrations expressed as micrograms per milliliter (µg/mL).

  • Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135, and Anti-PSY Antibody Concentrations Above Pre-defined Cut-off Values [ Time Frame: Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) ] [ Designated as safety issue: No ]
    The cut-off values assessed include greater than or equal to (≥) 0.3 micrograms per milliliter (µg/mL) and ≥ 2.0 µg/mL.

  • Anti-Tetanus Toxoid (TT) Antibody Concentrations [ Time Frame: Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) ] [ Designated as safety issue: No ]
    Concentrations were provided as Geometric Mean Concentrations expressed as International Units per milliliter (IU/mL).

  • Number of Subjects With Anti-tetanus Toxoid Antibody Concentrations Above the Pre-defines Cut-off Value [ Time Frame: Prior to and 1 month after vaccination with Nimenrix vaccine (Months 0 and 1) ] [ Designated as safety issue: No ]
    The cut-off value assessed was greater than or equal to 0.1 International Units per milliliter (IU/mL).

  • rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers at Month 7 [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    The rSBA titers were expressed as geometric mean titers.

  • Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers Above Predefined Cut-off Values at Month 7 [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    The cut-off values assessed were greater than or equal to (≥) 1:8 and ≥ 1:128.

  • Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY Antibody Concentrations at Month 7 [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Concentrations were provided as Geometric Mean Concentrations expressed as micrograms per milliliter (µg/mL).

  • Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY Antibody Concentrations Above Pre-defined Cut-off Values at Month 7 [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    The cut-off values assessed include greater than or equal to (≥) 0.3 micrograms per milliliter (µg/mL) and ≥ 2.0 µg/mL.

  • Immunoglobulin G (IgG) Anti-HAV Antibody Concentrations [ Time Frame: Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7) ] [ Designated as safety issue: No ]
    Concentrations are given as Geomatric Mean Concentrations expressed as milli-Internatinal Units per Milliliter (mIU/mL).

  • Number of Subjects With IgG Anti-HAV Antibody Concentrations Above the Pre-defined Cut-off Value [ Time Frame: Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7) ] [ Designated as safety issue: No ]
    The cut-off value assessed was greater than or equal to 15 milli-Internatinal Units per Milliliter (mIU/mL).

  • IgG Anti-HBs Antibody Concentrations [ Time Frame: Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7) ] [ Designated as safety issue: No ]
    Concentrations are given as Geomatric Mean Concentrations expressed as milli-Internatinal Units per Milliliter (mIU/mL).

  • Number of Subjects With IgG Anti-HB Antibody Concentrations Above the Pre-defined Cut-off Value [ Time Frame: Prior to the first dose (Month 0) and 1 month after the third dose of Twinrix vaccine (Month 7) ] [ Designated as safety issue: No ]
    The cut-off value assessed was greater than or equal to 10 milli-Internatinal Units per Milliliter (mIU/mL).

  • Number of Subjects Reporting Any Solicited Local Symptoms Post-meningococcal Vaccination [ Time Frame: During a 4-day period after Nimenrix vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed include pain, redness and swelling.

  • Number of Subjects Reporting Any Solicited Local Symptoms Post-Twinrix Vaccination [ Time Frame: During a 4-day period after each Twinrix vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed include pain, redness and swelling.

  • Number of Subjects Reporting Any Solicited General Symptoms [ Time Frame: During a 4-day period after any vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed include fatigue, fever (axillary temperature greater than or equal to 37.5 degrees Celcius), gastrointestinal symptoms and headache.

  • Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) [ Time Frame: Up to 1 month after each vaccine dose ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Any Specific AEs of New Onset of Chronic Illnesses [ Time Frame: During the entire study (up to Month 7) ] [ Designated as safety issue: No ]
    Specific AEs of new onset of chronic illnesses include e.g. autoimmune disorders, asthma, type I diabetes and allergies.

  • Number of Subjects Reporting Any Rash [ Time Frame: During the entire study (up to Month 7) ] [ Designated as safety issue: No ]
    Rashes include e.g. hives, idiopathic thrombocytopenic purpura, petechiae.

  • Number of Subjects Reporting Any Conditions Prompting Emergency Room Visits [ Time Frame: During the entire study (up to Month 7) ] [ Designated as safety issue: No ]
  • Number of Subjects Reporting Any Serious Adverse Events (SAEs) [ Time Frame: During the entire study (up to Month 7) ] [ Designated as safety issue: No ]
    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.


Enrollment: 611
Study Start Date: April 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nimenrix + Twinrix Group
Subjects received 1 dose of Nimenrix™ vaccine at Month 0 and 1 dose of Twinrix™ vaccine at Months 0, 1 and 6.
Biological: Nimenrix (Meningococcal vaccine 134612)
Single dose intramuscular injection
Biological: Twinrix
3-dose intramuscular injection. Twinrix Adult will be administered to subjects aged 16 years and above and Twinrix Junior will be administered to subjects aged from 11 years up to and including 15 years of age.
Active Comparator: Nimenrix Group
Subjects received 1 dose of Nimenrix™ vaccine at Month 0.
Biological: Nimenrix (Meningococcal vaccine 134612)
Single dose intramuscular injection
Active Comparator: Twinrix Group
Subjects received 1 dose of Twinrix™ vaccine at Months 0, 1 and 6.
Biological: Twinrix
3-dose intramuscular injection. Twinrix Adult will be administered to subjects aged 16 years and above and Twinrix Junior will be administered to subjects aged from 11 years up to and including 15 years of age.

Detailed Description:

All subjects of groups A and B will have 4 blood samples taken, all subjects of group C will have 3 blood samples taken.

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

  Eligibility

Ages Eligible for Study:   11 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that they and/or their parents/guardians can and will comply with the requirements of the protocol
  • A male or female between, and including, 11 and 17 years of age at the time of the first dose of vaccine.
  • Written informed consent obtained from the subject/ from the parent or guardian of the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Previously completed routine childhood vaccinations to the best of his/her/the parents'/guardians' knowledge.
  • If the subject is female and of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series.

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 dose of vaccine.
  • Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W-135 and/or Y within the last five years.
  • Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroup A, C, W-135 and/or Y.
  • Previous vaccination with tetanus toxoid within the last month.
  • Previous vaccination with hepatitis A and/or hepatitis B vaccine.
  • Seropositivity for hepatitis A IgG, hepatitis B surface antigen, hepatitis B core antibody and/or hepatitis B surface antigen at screening.
  • History of hepatitis A, hepatitis B and/or Neisseria meningitidis infection.
  • Known exposure to hepatitis A and/or hepatitis B virus within three months preceding the first dose of study vaccine.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition (congenital or secondary), including human immunodeficiency virus (HIV) infection, based on medical history and physical examination.
  • A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.
  • History of reactions or allergic disease likely to be exacerbated by any component of either vaccine.
  • 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 dose of study vaccine or planned administration during the study period.
  • Pregnant or lactating female.
  • History of chronic alcohol consumption and/or drug abuse.
  • Female planning to become pregnant or planning to discontinue contraceptive precautions.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00465816

Locations
Denmark
GSK Investigational Site
Aarhus N, Denmark, 8200
Sweden
GSK Investigational Site
Karlskrona, Sweden, SE-371 41
GSK Investigational Site
Linköping, Sweden, SE-581 85
GSK Investigational Site
Malmö, Sweden, SE-205 02
GSK Investigational Site
Umeå, Sweden, SE-901 85
GSK Investigational Site
Örebro, Sweden, SE-701 16
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Ostergaard L et al. The Candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugated vaccine (MenACWY-TT) co-administered with a combined hepatitis A and B vaccine (HepA/B) is immunogenic with an acceptable safety profile in subjects aged 11-17 Years. Abstract presented at the 3rd Northern European Conference on Travel Medicine (NECTM). Hamburg, Germany, 26-29 May 2010.
Ostergaard L et al. (2012) A tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when co-administered with Twinrix(®) in subjects aged 11-17 years: an open, randomised, controlled trial. Vaccine. 30(4):774-83.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00465816     History of Changes
Other Study ID Numbers: 109063
Study First Received: April 24, 2007
Results First Received: April 23, 2012
Last Updated: November 21, 2012
Health Authority: Sweden: Medical Products Agency

Keywords provided by GlaxoSmithKline:
non-inferiority
adolescents
meningococcal vaccine

ClinicalTrials.gov processed this record on April 17, 2014