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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00127855




Registration number
NCT00127855
Ethics application status
Date submitted
8/08/2005
Date registered
9/08/2005
Date last updated
27/08/2018

Titles & IDs
Public title
Dose Ranging Study of Combined Haemophilus Influenzae Type B-Meningococcal Serogroups CY (Hib-MenCY-TT) Vaccine
Scientific 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.
Secondary ID [1] 0 0
792014/002
Secondary ID [2] 0 0
792014/001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haemophilus Influenzae Type b 0 0
Neisseria Meningitidis 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Hib-MenCY-TT vaccine (MenHibrix)
Treatment: Other - Meningitec®
Treatment: Other - ActHIB®
Treatment: Other - Infanrix® Penta
Treatment: Other - Prevenar®
Treatment: Other - Mencevax® ACWY
Treatment: Other - PRP (Polyribosyl Ribitol Phosphate)

Experimental: MenHibrix Formulation 1 Group - Subjects were primed with MenHibrix formulation 1 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.

Experimental: MenHibrix Formulation 2 Group - Subjects were primed with MenHibrix formulation 2 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.

Experimental: MenHibrix Formulation 3 Group - Subjects were primed with MenHibrix formulation 3 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.

Active comparator: Menjugate Group - Subjects were primed with Menjugate co-administered with Infanrix Penta and ActiHIB according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.

Active comparator: ActHIB Group - Subjects were primed with ActHIB co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.


Treatment: Other: Hib-MenCY-TT vaccine (MenHibrix)
Three doses were administered intramuscularly (IM) in left thigh at Months 0,2 and 4 respectively

Treatment: Other: Meningitec®
Three doses were administered IM in right lower thigh at Months 0,2 and 4.

Treatment: Other: ActHIB®
Three doses were administered IM in left thigh at Months 0,2 and 4.

Treatment: Other: Infanrix® Penta
Three doses were administered IM in right upper thigh at Months 0,2 and 4 respectively.

Treatment: Other: Prevenar®
Three doses were administered IM in right lower thigh at Months 0,2 and 4 respectively.

Treatment: Other: Mencevax® ACWY
One fifth of one dose was administered IM in deltoid region of right arm at Month 10 as booster.

Treatment: Other: PRP (Polyribosyl Ribitol Phosphate)
One dose was administered IM in deltoid region of left arm at Month 10 as booster.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to 1 Milligram Per Milliliter
Timepoint [1] 0 0
One month after primary vaccination (Month 5)
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
One month after primary vaccination (Month 5)
Primary outcome [3] 0 0
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
Timepoint [3] 0 0
One month after primary vaccination (Month 5)
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup C (MenC) Titers
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Number of Subjects With rSBA-MenY Titers Greater Than or Equal to 1:8
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup Y (MenY) Titers
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Number of Subjects With Anti-polysaccharide C (PSC) Antibody Concentration Greater Than or Equal to 30 Micrograms Per Milliliter (µg/mL)
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Anti-polysaccharide C (PSC) Antibody Concentration
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Number of Subjects With Anti-polysaccharide Y (PSY) Antibody Concentration Greater Than or Equal to 30 Micrograms Per Milliliter (µg/mL)
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Anti-polysaccharide Y (PSY) Antibody Concentration
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Number of Subjects With Anti-PRP Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Anti-PRP Antibody Concentration
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Number of Subjects Seroprotected for Anti-diphtheria Antibodies
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Anti-diphtheria Antibody Concentrations
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Number of Subjects Seroprotected for Anti-tetanus Antibodies
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Anti-tetanus Antibody Concentrations
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Number of Subjects Seroseropositive for Anti-filamentus Haemagglutinin (FHA) Antibodies
Timepoint [15] 0 0
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)
Secondary outcome [16] 0 0
Anti- FHA Antibody Concentrations
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Number of Subjects Seroseropositive for Anti-pertactin (PRN) Antibodies
Timepoint [17] 0 0
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)
Secondary outcome [18] 0 0
Anti-PRN Antibody Concentrations
Timepoint [18] 0 0
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)
Secondary outcome [19] 0 0
Number of Subjects Seroseropositive for Anti-pertussis Toxoid (PT) Antibodies
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
Anti- PT Antibody Concentrations
Timepoint [20] 0 0
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)
Secondary outcome [21] 0 0
Number of Subjects Seroprotected for Anti-hepatitis B (HBs) Antibodies
Timepoint [21] 0 0
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)
Secondary outcome [22] 0 0
Anti- HBs Antibody Concentrations
Timepoint [22] 0 0
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)
Secondary outcome [23] 0 0
Number of Subjects Seroprotected for Anti-poliovirus Types 1, 2 and 3 Antibodies
Timepoint [23] 0 0
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)
Secondary outcome [24] 0 0
Anti-poliovirus Types 1, 2 and 3 Antibody Titers
Timepoint [24] 0 0
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)
Secondary outcome [25] 0 0
Number of Subjects With Anti-pneumococcal Antibody Concentrations Greater Than or Equal to Pre-defined Cut-off Values
Timepoint [25] 0 0
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)
Secondary outcome [26] 0 0
Anti-pneumococcal Antibody Concentrations
Timepoint [26] 0 0
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)
Secondary outcome [27] 0 0
Number of Subjects Reporting Solicited Local and General Symptoms During the Primary Vaccination Course
Timepoint [27] 0 0
During the 8-Day (Day 0-7) follow-up period after any vaccine dose during the primary vaccination course
Secondary outcome [28] 0 0
Number of Subjects Reporting Solicited Local and General Symptoms After Administration of the Polysaccharide Challenge Dose
Timepoint [28] 0 0
During the 8-Day (Day 0-7) follow-up period after the polysaccharide challenge dose
Secondary outcome [29] 0 0
Number of Subjects Reporting Unsolicited Adverse Events During the Primary Vaccination Course
Timepoint [29] 0 0
During the 31-Day (Day 0-30) follow-up period after any vaccine dose during the primary vaccination course
Secondary outcome [30] 0 0
Number of Subjects Reporting Unsolicited Adverse Events After Administration of the Polysaccharide Challenge Dose
Timepoint [30] 0 0
During the 31-Day (Day 0-30) follow-up period after administration of the polysaccharide challenge dose
Secondary outcome [31] 0 0
Number of Subjects Reporting Serious Adverse Events During the Primary Vaccination Course
Timepoint [31] 0 0
Up to one month after the 3-dose primary vaccination course (Month 5)
Secondary outcome [32] 0 0
Number of Subjects Reporting Serious Adverse Events After Administration of the Polysaccharide Challenge Dose
Timepoint [32] 0 0
Up to one month following administration of the polysaccharide challenge dose (Month 11)

Eligibility
Key inclusion 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.
Minimum age
6 Weeks
Maximum age
12 Weeks
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/02/2004
Sample size
Target
Accrual to date
Final
409
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - North Adelaide
Recruitment hospital [2] 0 0
GSK Investigational Site - Carlton
Recruitment hospital [3] 0 0
GSK Investigational Site - Subiaco
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment postcode(s) [2] 0 0
3053 - Carlton
Recruitment postcode(s) [3] 0 0
6018 - Subiaco

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00127855
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00127855