Clinical trial NCT00127855: Dose Ranging Study of Combined Haemophilus Influenzae Type B-Meningococcal Serogroups CY (Hib-MenCY-TT) Vaccine
Official title: A Phase II, Open (Partially Double-blind), Randomised, Controlled, Multicentre, Primary Vaccination Study to Evaluate the Immunogenicity (Including Immune Memory), Reactogenicity and Safety of Three Different Formulations of the GSK Biologicals' Combined Haemophilus Influenzae Type B-meningococcal Serogroups CY Conjugate Vaccine Given Concomitantly With Infanrix® Penta and Prevenar®, Versus ActHIB® and Meningitec® Given Concomitantly With Infanrix® Penta and Versus ActHIB® Given Concomitantly With Infanrix® Penta and Prevenar® in Infants According to a 2-4-6 Month Schedule.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Haemophilus Influenzae Type b
Neisseria Meningitidis
Keywords: Invasive bacterial disease caused by Hib
Neisseria meningitidis serogroups C & Y
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-08-09
Enrollment: 409
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 evaluated the safety and immunogenicity of 3 formulations of Hib-MenCY-TT vaccine compared to 2 control groups receiving licensed meningococcal serogroup C conjugate vaccine and/or licensed Hib conjugate vaccine administered at 2, 4, and 6 months of age. Antibody persistence and immune responses to polysaccharide vaccine boosters were additionally assessed at 11 to 14 months of age.


Eligibility criteria: Inclusion criteria:

* A male or female between, and including, 6 and 12 weeks (42-90 days) 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.
* Vaccinated against hepatitis B at birth.
* Born after a gestation period of 36 - 42 weeks.

Exclusion criteria:

* Use of any investigational or non-registered 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 of immunosuppressants or other immune-modifying drugs since birth
* Any chronic drug therapy to be continued during the study period.
* Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the first dose of vaccine(s).
* Previous vaccination against diphtheria, tetanus, pertussis, polio, N. meningitidis of serogroups C and Y, Haemophilus influenzae type b or Streptococcus pneumoniae.
* History of or known exposure to diphtheria, tetanus, pertussis, polio, or invasive diseases due to N. meningitidis of serogroups C and Y, Haemophilus influenzae type b or Streptococcus pneumoniae.
* 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 vaccines.
* 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.

Primary outcomes:
measure: Number of Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to 1 Milligram Per Milliliter
timeFrame: One month after primary vaccination (Month 5)
measure: Number of Subjects With Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup C (MenC) Titers Greater Than or Equal to 1:8
timeFrame: One month after primary vaccination (Month 5)
measure: Number of Subjects With Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup Y (MenY) Titers Greater Than or Equal to 1:8
timeFrame: One month after primary vaccination (Month 5)
Secondary outcomes:
measure: Number of Subjects With Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup C (MenC) Titers Greater Than or Equal to 1:8
timeFrame: Prior to vaccination (Day 0), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup C (MenC) Titers
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Number of Subjects With rSBA-MenY Titers Greater Than or Equal to 1:8
timeFrame: Prior to vaccination (Day 0), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup Y (MenY) Titers
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Number of Subjects With Anti-polysaccharide C (PSC) Antibody Concentration Greater Than or Equal to 30 Micrograms Per Milliliter (µg/mL)
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Anti-polysaccharide C (PSC) Antibody Concentration
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Number of Subjects With Anti-polysaccharide Y (PSY) Antibody Concentration Greater Than or Equal to 30 Micrograms Per Milliliter (µg/mL)
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Anti-polysaccharide Y (PSY) Antibody Concentration
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Number of Subjects With Anti-PRP Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Anti-PRP Antibody Concentration
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11)
measure: Number of Subjects Seroprotected for Anti-diphtheria Antibodies
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Anti-diphtheria Antibody Concentrations
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Number of Subjects Seroprotected for Anti-tetanus Antibodies
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Anti-tetanus Antibody Concentrations
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Number of Subjects Seroseropositive for Anti-filamentus Haemagglutinin (FHA) Antibodies
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Anti- FHA Antibody Concentrations
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Number of Subjects Seroseropositive for Anti-pertactin (PRN) Antibodies
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Anti-PRN Antibody Concentrations
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Number of Subjects Seroseropositive for Anti-pertussis Toxoid (PT) Antibodies
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Anti- PT Antibody Concentrations
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Number of Subjects Seroprotected for Anti-hepatitis B (HBs) Antibodies
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Anti- HBs Antibody Concentrations
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Number of Subjects Seroprotected for Anti-poliovirus Types 1, 2 and 3 Antibodies
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Anti-poliovirus Types 1, 2 and 3 Antibody Titers
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Number of Subjects With Anti-pneumococcal Antibody Concentrations Greater Than or Equal to Pre-defined Cut-off Values
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Anti-pneumococcal Antibody Concentrations
timeFrame: Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10)
measure: Number of Subjects Reporting Solicited Local and General Symptoms During the Primary Vaccination Course
timeFrame: During the 8-Day (Day 0-7) follow-up period after any vaccine dose during the primary vaccination course
measure: Number of Subjects Reporting Solicited Local and General Symptoms After Administration of the Polysaccharide Challenge Dose
timeFrame: During the 8-Day (Day 0-7) follow-up period after the polysaccharide challenge dose
measure: Number of Subjects Reporting Unsolicited Adverse Events During the Primary Vaccination Course
timeFrame: During the 31-Day (Day 0-30) follow-up period after any vaccine dose during the primary vaccination course
measure: Number of Subjects Reporting Unsolicited Adverse Events After Administration of the Polysaccharide Challenge Dose
timeFrame: During the 31-Day (Day 0-30) follow-up period after administration of the polysaccharide challenge dose
measure: Number of Subjects Reporting Serious Adverse Events During the Primary Vaccination Course
timeFrame: Up to one month after the 3-dose primary vaccination course (Month 5)
measure: Number of Subjects Reporting Serious Adverse Events After Administration of the Polysaccharide Challenge Dose
timeFrame: Up to one month following administration of the polysaccharide challenge dose (Month 11)
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: Subiaco
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: Nolan T, Lambert S, Roberton D, Marshall H, Richmond P, Streeton C, Poolman J, Boutriau D. A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine is immunogenic and induces immune memory when co-administered with DTPa-HBV-IPV and conjugate pneumococcal vaccines in infants. Vaccine. 2007 Dec 12;25(51):8487-99. doi: 10.1016/j.vaccine.2007.10.013. Epub 2007 Oct 25.
citation: T Nolan et al. A novel Haemophilus influenzae type b - meningococcal serogroups C and Y conjugate (Hib-MenCY-TT) vaccine induces persistent immune responses and immune memory. Abstract presented at Pediatric Academic Societies' (PAS) Annual meeting. San Francisco, California, US, 29 April to 2 May 2006.