Clinical trial NCT00134719: Hib-MenCY-TT Vaccine Study Compared to Licensed Hib and Meningococcal Serogroup C Conjugate Vaccines
Official title: A Multicentre Primary & Booster Vaccination Study of GSK Biologicals' Hib-MenCY-TT Conjugate Vaccine vs ActHIB® & MenC Conjugate Licensed Vaccine When Given According to the 2-4-6 Month Schedule to Healthy Infants With Booster Dose at 12 to 15 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neisseria Meningitidis
Haemophilus Influenzae Type b
Keywords: Invasive Hib & N. meningitidis diseases
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-08-25
Enrollment: 1104
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is evaluating the safety and immunogenicity of Hib-MenCY-TT vaccine compared to control groups receiving licensed Hib or MenC conjugate vaccines, each administered at 2, 4, 6, and 12 to 15 months of age. Co-administration with live, attenuated measles, mumps, and rubella combination vaccine; and with live, attenuated varicella vaccine will be assessed with administration of the booster dose. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, September 2007.

Detailed description: The study will be conducted in 2 stages: a 3-dose primary vaccination at 2, 4 and 6 months of age and a booster vaccination at 12 to 15 months of age. All subjects will have 3 blood samples taken. Half of the subjects of each group will have a blood sample taken just prior to the administration of the third dose of the primary vaccination and the other half of the subjects of each group will have a blood sample taken at one month after the third vaccine dose of the primary vaccination phase. In addition, all subjects of all groups will have a blood sample taken before and 42 days after administration of the booster dose.

Eligibility criteria: Inclusion Criteria:

* Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
* A male or female between, and including, 6 and 12 weeks 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.
* Born after a gestation period between 36 and 42 weeks.

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 since birth.
* Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s).
* Previous vaccination against Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, poliovirus, and/or Streptococcus pneumoniae; more than one previous dose of hepatitis B vaccine. Vaccination with hepatitis B at birth is accepted (although not mandatory). Influenza vaccination is allowed 30 days after administration of the third vaccine dose to 30 days preceding the booster dose.
* History of Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Streptococcus pneumoniae and/or varicella invasive disease.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s), including dry natural latex rubber, tetanus toxoid, diphtheria toxoid, neomycin, polymyxin.
* 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 since birth or planned administration during the study period.
* Additional specific criteria for the booster part of the study
* History of or previous vaccination against measles, mumps, rubella or varicella.
* Previous booster vaccination with Hib or meningococcal serogroup C vaccine since the last visit of the primary phase.

Primary outcomes:
measure: Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Concentration Greater Than or Equal to 1.0 Microgram Per Milliliter (µg/mL)
timeFrame: One month after the 3-dose primary vaccination course
measure: Number of Subjects With Meningococcal Polysaccharide C Serum Bactericidal Activity/Assay Using Baby Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to 1:128
timeFrame: One month after the 3-dose primary vaccination course
measure: Number of Subjects Seroconverted for Anti-measles Antibodies
timeFrame: 42 days after the fourth dose vaccination
measure: Number of Subjects Seroconverted for Anti-mumps Antibodies
timeFrame: 42 days after the fourth dose vaccination
measure: Number of Subjects With an Anti-rubella Seroresponse
timeFrame: 42 days after the fourth dose vaccination
measure: Number of Subjects Seroconverted for Anti-varicella Antibodies
timeFrame: 42 days after the fourth dose vaccination
Secondary outcomes:
measure: Number of Subjects With rSBA-MenC Titer Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: rSBA-MenC Titers
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Number of Subjects With rSBA-MenY Titer Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: rSBA-MenY Titers
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Number of Subjects With Meningococcal Polysaccharide C Serum Bactericidal Activity/Assay Using Human Complement (hSBA-MenC) Antibody Titer Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: hSBA-MenC Titers
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Number of Subjects With Meningococcal Polysaccharide Y Serum Bactericidal Activity/Assay Using Human Complement (hSBA-MenY) Antibody Titer Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: hSBA-MenY Titers
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Number of Subjects With Anti-Polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Anti-PSC Concentrations
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Number of Subjects With Anti-Polysaccharide Y (Anti-PSY) Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Anti-PSY Concentrations
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Number of Subjects With Anti-PRP Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Anti-PRP Concentrations
timeFrame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
measure: Number of Subjects With Anti-measles Concentration Greater Than or Equal to 150 mIU/mL
timeFrame: Just prior to the fourth dose and 42 days after the fourth dose
measure: Number of Subjects With Anti-mumps Titer Greater Than or Equal to 24 ED50
timeFrame: Just prior to the fourth dose and 42 days after the fourth dose
measure: Number of Subjects With Anti-rubella Concentration Greater Than or Equal to 4 IU/mL
timeFrame: Just prior to the fourth dose and 42 days after the fourth dose
measure: Number of Subjects With Anti-varicella Titer Greater Than or Equal to 1:5
timeFrame: Just prior to the fourth dose and 42 days after the fourth dose
measure: Number of Subjects With a Fourth Dose Response for hSBA-MenC
timeFrame: 42 days after the fourth dose
measure: Number of Subjects With a Fourth Dose Response for hSBA-MenY
timeFrame: 42 days after the fourth dose
measure: Number of Subjects With Anti-measles Concentration Greater Than or Equal to Predefined Cut-off Values in Initially Seronegative Subjects
timeFrame: 42 days after the fourth dose
measure: Anti-measles Concentrations in Initially Seronegative Subjects
timeFrame: 42 days after the fourth dose
measure: Number of Subjects With Anti-rubella Concentration Greater Than or Equal to Predefined Cut-off Values in Initially Seronegative Subjects
timeFrame: 42 days after the fourth dose
measure: Anti-rubella Concentrations in Initially Seronegative Subjects
timeFrame: 42 days after the fourth dose
measure: Number of Subjects With Anti-mumps Titer Greater Than or Equal to 28 ED50 in Subjects With Anti-mumps Titer Below 28 ED50 Before Vaccination
timeFrame: 42 days after the fourth dose
measure: Number of Subjects With Anti-mumps Titer Greater Than or Equal to Predefined Cut-off Values in Initially Seronegative Subjects
timeFrame: 42 days after the fourth dose
measure: Anti-mumps Titers in Initially Seronegative Subjects
timeFrame: 42 days after the fourth dose
measure: Number of Subjects With Anti-varicella Titer Greater Than or Equal to Predefined Cut-off Values in Initially Seronegative Subjects
timeFrame: 42 days after the fourth dose
measure: Anti-varicella Titers in Initially Seronegative Subjects
timeFrame: 42 days after the fourth dose
measure: Number of Subjects Reporting Solicited Local and General Symptoms During the Primary Vaccination Phase
timeFrame: During a 4-day period (Day 0-3) after any vaccine dose in the primary vaccination phase
measure: Number of Subjects Reporting Solicited Local and General Symptoms During the Fourth Dose Vaccination Phase
timeFrame: During a 4-day period (Day 0-3) after the fourth dose vaccination phase
measure: Number of Subjects Reporting Unsolicited Adverse Events
timeFrame: During the 31-day (Day 0-30) post-primary and post-fourth dose vaccination period
measure: Number of Subjects Reporting Specific Solicited General AEs Related to Measles, Mumps, Rubella Vaccine and Varicella Vaccine
timeFrame: During a 43-day (Day 0-42) after the fourth dose
measure: Number of Subjects Reporting Serious Adverse Events (SAEs), New Onset of Chronic Illnesses (NOCI), Rash, Emergency Room Visits (ER), Physician Office Visits (PO) During the Primary Vaccination Phase
timeFrame: From enrolment through the day preceding the fourth dose
measure: Number of Subjects Reporting Serious Adverse Events (SAEs), New Onset of Chronic Illnesses (NOCI), Rash, Emergency Room Visits (ER), Physician Office Visits (PO) During the Fourth Dose Vaccination Phase
timeFrame: From the day of administration of the fourth dose until the end of the extended safety follow-up period (last study contact at 18-21 months of age
Other outcomes:
Locations:
city: North Adelaide
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Carlton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Perth
country: Australia
facility: GSK Investigational Site
state: Western Australia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bryant KA, Marshall GS. Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers. Expert Rev Vaccines. 2011 Jul;10(7):941-50. doi: 10.1586/erv.11.90.
citation: Bryant K, McVernon J, Marchant C, Nolan T, Marshall G, Richmond P, Marshall H, Nissen M, Lambert S, Aris E, Mesaros N, Miller J. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials. Hum Vaccin Immunother. 2012 Aug;8(8):1036-41. doi: 10.4161/hv.20357. Epub 2012 Aug 1.
citation: Nolan T, Richmond P, Marshall H, McVernon J, Alexander K, Mesaros N, Aris E, Miller J, Poolman J, Boutriau D. Immunogenicity and safety of an investigational combined haemophilus influenzae type B-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine. Pediatr Infect Dis J. 2011 Mar;30(3):190-6. doi: 10.1097/INF.0b013e3181fcb2bf.