3 Formulations of Hib-MenCY-TT Vaccine & 1 Formulation of Hib-MenC-TT Vaccine Compared to Licensed Meningococcal Serogroup C Conjugate Vaccine, Each Administered at 2,3,4 Mths of Age

Study Overview
=================
Brief Summary
-----------------
This study evaluated the safety and immunogenicity of 3 formulations of Hib-MenCY-TT vaccine and 1 formulation of Hib-MenC-TT vaccine compared to a control group receiving licensed meningococcal serogroup C conjugate vaccine, each administered at 2, 3, and 4 months of age. Antibody persistence and immune responses to booster vaccinations were additionally assessed at 12 to 18 months of age.

Detailed Description
-----------------
Primary & booster vaccination study to evaluate the immuno,reacto & safety of 3 diff. formulations of GSKBio'combined Haemophilus influenzae typeb-meningococcal serogroups C & Y-conjugate vaccine & one formulation of GSKBio' Haemophilus influenzae typeb-meningococcal serogroup C conjugate vaccine each given concomitantly With Infanrix penta (DTaP-IPV-HepB vaccine), vs Meningitec meningococcal SerogroupC conj.vaccine) given concomitantly With Infanrix hexa (DTaP-IPV-HepB-Hib vaccine) in infants according a 2-3-4 mth schedule

Official Title
-----------------
A Phase II, Open (Partially Double-blind), Randomised, Controlled, Multicentre, Primary Vaccination Study to Evaluate the Immunogenicity, Reactogenicity and Safety of Three Different Formulations of GSK Biologicals' Combined Haemophilus Influenzae Type B-meningococcal Serogroups C and Y- Conjugate Vaccine and One Formulation of GSK Biologicals' Haemophilus Influenzae Type B-meningococcal Serogroup C Conjugate Vaccine Each Given Concomitantly With InfanrixTM Penta, Versus MeningitecTM, Given Concomitantly With InfanrixTM Hexa in Infants According to a 2-3-4 Month Schedule

Conditions
-----------------
Haemophilus Influenzae Type b, Neisseria Meningitidis

Intervention / Treatment
-----------------
* Biological: Hib-MenCY-TT vaccine
* Biological: Hib-MenC-TT vaccine
* Biological: Menjugate ®
* Biological: Infanrix penta ®
* Biological: Infanrix hexa ®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy infants without major congenital illness, immunosuppression, or chronic disease born at 36 to 42 weeks of gestation, between 6 and 12 weeks of age at enrollment, and vaccinated against hepatitis B at birth. Exclusion Criteria: Infants should not have received any investigational drug, vaccine, chronic immunosuppressants, or immunoglobulin or blood products.

Ages Eligible for Study
-----------------
Minimum Age: 6 Weeks
Maximum Age: 12 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Menhibrix F1/Infanrix-penta Group<br>Subjects received Menhibrix vaccine formulation 1 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively. | Biological: Hib-MenCY-TT vaccine<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in left thigh.<br>Biological: Infanrix penta ®<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in right thigh.<br>* Other names: DTPa-HBV-IPV vaccine;|
| Experimental: Menhibrix F2/Infanrix-penta Group<br>Subjects received Menhibrix vaccine formulation 2 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively. | Biological: Hib-MenCY-TT vaccine<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in left thigh.<br>Biological: Infanrix penta ®<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in right thigh.<br>* Other names: DTPa-HBV-IPV vaccine;|
| Experimental: Menhibrix F3/Infanrix-penta Group<br>Subjects received Menhibrix vaccine formulation 3 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively. | Biological: Hib-MenCY-TT vaccine<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in left thigh.<br>Biological: Infanrix penta ®<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in right thigh.<br>* Other names: DTPa-HBV-IPV vaccine;|
| Experimental: Menitorix/Infanrix-penta Group<br>Subjects received Menitorix vaccine and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menitorix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively. | Biological: Hib-MenC-TT vaccine<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in left thigh.<br>Biological: Infanrix penta ®<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in right thigh.<br>* Other names: DTPa-HBV-IPV vaccine;|
| Active Comparator: Menjugate/Infanrix-hexa Group<br>Subjects received Menjugate vaccine and Infanrix-hexa vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menjugate and Infanrix-hexa vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively. | Biological: Menjugate ®<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in left thigh.<br>Biological: Infanrix hexa ®<br>* Three doses during the primary vaccination and one booster dose administered intramuscularly (IM) in right thigh.<br>* Other names: DTPa-HBV-IPV/Hib vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1 Microgram Per Millilitre (µg/mL). | Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 1 microgram per millilitre (µg/mL) | One month after dose 3 (at study Month 3 - primary phase) | 
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titre Equal to or Above 1:8 | rSBA-MenC antibody titre cut-off value assessed was ≥1:8 | One month after dose 3 (at study Month 3 - primary phase) | 
| Number of Subjects With Meningococcal Serogroup Y Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenY) Titre Equal to or Above 1:8 | rSBA-MenY antibody titre cut-off value assessed was ≥1:8 | One month after dose 3 (at study Month 3 - primary phase) | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1 Microgram Per Millilitre (µg/mL). | Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 1 microgram per millilitre (µg/mL) | One month after the booster vaccination (at study Month 1 - booster phase) | 
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titre Equal to or Above 1:8 | rSBA-MenC antibody titre cut-off value assessed was ≥1:8 | One month after the booster vaccination (at study Month 1 - booster phase) | 
| Number of Subjects With Meningococcal Serogroup Y Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenY) Titre Equal to or Above 1:8 | rSBA-MenY antibody titre cut-off value assessed was ≥1:8 | One month after the booster vaccination (at study Month 1 - booster phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titre Equal to or Above 1:8 | rSBA-MenC antibody titre cut-off value assessed was ≥1:8 | Before the administration of the first dose (at pre-vaccination = study Month 0 - primary phase) | 
| Number of Subjects With Meningococcal Serogroup Y Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenY) Titre Equal to or Above 1:8 | rSBA-MenY antibody titre cut-off value assessed was ≥1:8 | Before the administration of the first dose (at pre-vaccination = study Month 0 - primary phase) | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1 Microgram Per Millilitre (µg/mL). | Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 1 microgram per millilitre (µg/mL) | Before the administration of the first dose (at pre-vaccination = study Month 0 - primary phase) | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1 Microgram Per Millilitre (µg/mL). | Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 1 microgram per millilitre (µg/mL) | Prior to the booster vaccination (at study Month 0 - booster phase) | 
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titre Equal to or Above 1:8 | rSBA-MenC antibody titre cut-off value assessed was ≥1:8 | Prior to the booster vaccination (at study Month 0 - booster phase) | 
| Number of Subjects With Meningococcal Serogroup Y Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenY) Titre Equal to or Above 1:8 | rSBA-MenY antibody titre cut-off value assessed was ≥1:8 | Prior to the booster vaccination (at study Month 0 - booster phase) | 
| rSBA-MenC Antibody Titres | Titres are expressed as geometric mean titres (GMTs) | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| rSBA-MenY Antibody Titres | Titres are expressed as geometric mean titres (GMTs) | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 0.15 Microgram Per Millilitre (µg/mL). | Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 0.15 microgram per millilitre (µg/mL) | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Anti-PRP Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL. | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Equal to or Above 0.30 Microgram Per Millilitre (µg/mL) | Anti-PSC antibody concentration cut-off value assessed was ≥0.30 µg/mL | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Number of Subjects With Anti-polysaccharide Y (Anti-PSY) Antibody Concentration Equal to or Above 0.30 Microgram Per Millilitre (µg/mL) | Anti-PSY antibody concentration cut-off value assessed was ≥0.30 µg/mL | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Anti-PSC Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL. | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Anti-PSY Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL. | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Anti-tetanus Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in International Units per millilitre (IU/mL). | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Anti-filamentous Haemagglutinin (Anti-FHA), Anti-pertactin (Anti-PRN), Anti-pertussis Toxoid (Anti-PT) Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in Enzyme-Linked Immunosorbent Assay (ELISA) Units per millilitre. | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Number of Seroprotected Subjects for Anti-tetanus Antibodies | Seroprotection status is defined as anti-tetanus toxoid antibody concentration ≥ 0.1 International Units per millilitre (IU/mL) | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Number of Subjects With Anti-FHA, Anti-PRN and Anti-PT Antibody Concentration Equal to or Above 5 Enzyme-Linked Immunosorbent Assay (ELISA) Units Per Millilitre (EL.U/mL) | Anti-FHA, anti-PRN and anti-PT antibody concentration cut-off value assessed was ≥ 5 ELISA units per millilitre. | Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase) | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 0.15 Microgram Per Millilitre (µg/mL). | Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 0.15 microgram per millilitre (µg/mL) | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Anti-PRP Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL. | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titre Equal to or Above 1:128 | rSBA-MenC antibody titre cut-off value assessed was ≥1:128 | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Number of Subjects With Meningococcal Serogroup Y Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenY) Titre Equal to or Above 1:128 | rSBA-MenY antibody titre cut-off value assessed was ≥1:128 | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| rSBA-MenC Antibody Titres | Titres are expressed as geometric mean titres (GMTs) | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| rSBA-MenY Antibody Titres | Titres are expressed as geometric mean titres (GMTs) | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Equal to or Above 0.30 Microgram Per Millilitre (µg/mL) | Anti-PSC antibody concentration cut-off value assessed was ≥0.30 µg/mL | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Equal to or Above 2.0 Microgram Per Millilitre (µg/mL) | Anti-PSC antibody concentration cut-off value assessed was ≥2.0 µg/mL | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Anti-PSC Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL. | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Anti-PSY Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL. | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Number of Subjects With Anti-tetanus Toxoid (Anti-T) Antibody Concentration Equal to or Above 0.1 International Units Per Millilitre (IU/mL). | Anti-tetanus toxoid antibody concentration cut-off value assessed was ≥ 0.1 IU/mL | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Anti-T Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in International Units per millilitre (IU/mL). | Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase) | 
| Anti-diphtheria Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in IU/mL. | One month after the third dose (at study Month 3 - primary phase) | 
| Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | Antibody concentrations are expressed as geometric mean concentrations (GMCs) in milli-International Units per millilitre (mIU/mL). | One month after the third dose (at study Month 3 - primary phase) | 
| Anti-poliovirus Types 1, 2, 3 Antibody Titres | Titres are expressed as geometric mean titres (GMTs) | One month after the third dose (at study Month 3 - primary phase) | 
| Number of Seroprotected Subjects for Anti-diphtheria Antibodies | Seroprotection status is defined as anti-diphtheria antibody concentrations ≥ 0.1 IU/mL | One month after the third dose (at study Month 3 - primary phase) | 
| Number of Seroprotected Subjects for Anti-hepatitis B Antibodies | Seroprotection status is defined as anti-HBs antibody concentrations ≥ 10 mIU/mL | One month after the third dose (at study Month 3 - primary phase) | 
| Number of Seroprotected Subjects for Anti-poliovirus Types 1, 2 and 3 Antibodies | Seroprotection status is defined as anti-polio 1, 2 and 3 antibody titres ≥ 1:8 | One month after the third dose (at study Month 3 - primary phase) | 
| Number of Subjects With Vaccine Response to PT, FHA and PRN | Vaccine response rates are defined as appearance of antibodies in subjects who were initially seronegative (i.e., with concentrations < cut-off value) or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e., with concentrations ≥ cut-off value), taking into consideration the decreasing maternal antibodies. | One month after the third dose (at study Month 3 - primary phase) | 
| Number of Subjects With Solicited Local Symptoms | Solicited local symptoms assessed were pain, redness and swelling. | During the 8-day (Day 0-7) follow-up period (during the primary phase) | 
| Number of Subjects With Solicited General Symptoms | Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (fever is defined as rectal temperature ≥ 38.0 degrees Celsius (°C)). | During the 8-day (Day 0-7) follow-up period (during the primary phase) | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. | During the 31-day (Day 0-30) follow-up period (during the primary phase) | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. | Over the full course of the primary phase (up to study Month 3 - primary phase) | 
| Number of Subjects With Solicited Local Symptoms | Solicited local symptoms assessed were pain, redness and swelling. | During the 8-day (Day 0-7) follow-up period (during the booster phase) | 
| Number of Subjects With Solicited General Symptoms | Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (fever is defined as rectal temperature ≥ 38.0 degrees Celsius (°C)). | During the 8-day (Day 0-7) follow-up period (during the booster phase) | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. | During the 31-day (Day 0-30) follow-up period (during the booster phase) | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. | Over the full course of the booster phase (up to study Month 1 - booster phase) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Invasive bacterial disease caused by Hib, Neisseria meningitidis serogroups C & Y