Dose Ranging Study of Combined Haemophilus Influenzae Type B-Meningococcal Serogroups CY (Hib-MenCY-TT) Vaccine

Haemophilus Influenzae Type b Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00127855
• Other study ID #: 792014/001
• Secondary ID: 792014/002
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2003
• Est. completion date: February 12, 2004

Study information

• Verified date: October 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 409
• Est. completion date: February 12, 2004
• Est. primary completion date: February 1, 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 12 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• Haemophilus Infections
• Haemophilus Influenzae Type b
• Influenza, Human
• Neisseria Meningitidis

Intervention

Biological:
• Hib-MenCY-TT vaccine (MenHibrix)
Three doses were administered intramuscularly (IM) in left thigh at Months 0,2 and 4 respectively
• Meningitec®
Three doses were administered IM in right lower thigh at Months 0,2 and 4.
• ActHIB®
Three doses were administered IM in left thigh at Months 0,2 and 4.
• Infanrix® Penta
Three doses were administered IM in right upper thigh at Months 0,2 and 4 respectively.
• Prevenar®
Three doses were administered IM in right lower thigh at Months 0,2 and 4 respectively.
• Mencevax® ACWY
One fifth of one dose was administered IM in deltoid region of right arm at Month 10 as booster.
• PRP (Polyribosyl Ribitol Phosphate)
One dose was administered IM in deltoid region of left arm at Month 10 as booster.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Carlton	Victoria
Australia	GSK Investigational Site	North Adelaide	South Australia
Australia	GSK Investigational Site	Subiaco	Western Australia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Australia, 

References & Publications (3)

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. Review. — View 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. Epub 2007 Oct 25. — View 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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to 1 Milligram Per Milliliter	The cut-off concentration assessed was 1 milligram per milliliter (mg/mL).	One month after primary vaccination (Month 5)
Primary	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	The cut-off titer assessed was a dilution of 1:8. Titers were expressed as the reciprocal of the dilution resulting in 50 percent inhibition.	One month after primary vaccination (Month 5)
Primary	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	The cut-off titer assessed was a dilution of 1:8. Titers were expressed as the reciprocal of the dilution resulting in 50 percent inhibition.	One month after primary vaccination (Month 5)
Secondary	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	The cut-off titer assessed was a dilution of 1:8. Titers were expressed as the reciprocal of the dilution resulting in 50 percent inhibition.	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	Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup C (MenC) Titers	Titers were presented as geometric mean titers (GMTs) expressed as the reciprocal of the dilution resulting in 50 percent inhibition.	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	Number of Subjects With rSBA-MenY Titers Greater Than or Equal to 1:8	The cut-off titer assessed was a dilution of 1:8. Titers were expressed as the reciprocal of the dilution resulting in 50 percent inhibition.	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	Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup Y (MenY) Titers	Titers were presented as geometric mean titers (GMTs) expressed as the reciprocal of the dilution resulting in 50 percent inhibition.	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	Number of Subjects With Anti-polysaccharide C (PSC) Antibody Concentration Greater Than or Equal to 30 Micrograms Per Milliliter (µg/mL)	The cut-off concentration assessed was 30 micrograms per milliliter (µg/mL).	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	Anti-polysaccharide C (PSC) Antibody Concentration	Titers are presented as Geometric Mean Titers (GMTs) expressed as micrograms per milliliter (µg/mL).	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	Number of Subjects With Anti-polysaccharide Y (PSY) Antibody Concentration Greater Than or Equal to 30 Micrograms Per Milliliter (µg/mL)	The cut-off concentration assessed was 30 micrograms per milliliter (µg/mL).	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	Anti-polysaccharide Y (PSY) Antibody Concentration	Titers are presented as Geometric Mean Titers (GMTs) expressed as micrograms per milliliter (µg/mL).	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	Number of Subjects With Anti-PRP Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values	The cut-off concentrations assessed were 0.15 micrograms per milliliter (µg/mL) and 1 µg/mL.	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	Anti-PRP Antibody Concentration	Concentrations are presented as GMCs and expressed as µg/mL.	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	Number of Subjects Seroprotected for Anti-diphtheria Antibodies	Seroprotection is defined as anti-diphtheria toxoid antibody concentration greater than or equal to 0.1 International Units per Milliliter (IU/mL).	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	Anti-diphtheria Antibody Concentrations	Concentrations are presented as GMCs and expressed as International Units per Milliliter (IU/mL).	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	Number of Subjects Seroprotected for Anti-tetanus Antibodies	Seroprotection is defined as anti-tetanus toxoid antibody concentration greater than or equal to 0.1 International Units per Milliliter (IU/mL).	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	Anti-tetanus Antibody Concentrations	Concentrations are presented as GMCs and expressed as International Units per Milliliter (IU/mL).	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	Number of Subjects Seroseropositive for Anti-filamentus Haemagglutinin (FHA) Antibodies	Seropositivity is defined as anti-FHA antibody concentration greater than or equal to 5 Enzyme-Linked Immunosorbent Assay (ELISA) Units per Milliliter (EL.U/mL).	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	Anti- FHA Antibody Concentrations	Concentrations are presented as GMCs and expressed as Enzyme-Linked Immunosorbent Assay (ELISA) Units per Milliliter (EL.U/mL).	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	Number of Subjects Seroseropositive for Anti-pertactin (PRN) Antibodies	Seropositivity is defined as anti-PRN antibody concentration greater than or equal to 5 Enzyme-Linked Immunosorbent Assay (ELISA) Units per Milliliter (EL.U/mL).	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	Anti-PRN Antibody Concentrations	Concentrations are presented as GMCs and expressed as Enzyme-Linked Immunosorbent Assay (ELISA) Units per Milliliter (EL.U/mL).	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	Number of Subjects Seroseropositive for Anti-pertussis Toxoid (PT) Antibodies	Seropositivity is defined as anti-PT antibody concentration greater than or equal to 5 Enzyme-Linked Immunosorbent Assay (ELISA) Units per Milliliter (EL.U/mL).	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	Anti- PT Antibody Concentrations	Concentrations are presented as GMCs and expressed as Enzyme-Linked Immunosorbent Assay (ELISA) Units per Milliliter (EL.U/mL).	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	Number of Subjects Seroprotected for Anti-hepatitis B (HBs) Antibodies	Seroprotection is defined as anti-HBs antibody concentration greater than or equal to 10 Milli-International Units per Milliliter (mIU/mL).	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	Anti- HBs Antibody Concentrations	Concentrations are presented as GMCs and expressed as Milli-International Units per Milliliter (mIU/mL).	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	Number of Subjects Seroprotected for Anti-poliovirus Types 1, 2 and 3 Antibodies	Seroprotection is defined as anti-polio antibody titer greater than or equal to 1:8 dilution.	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	Anti-poliovirus Types 1, 2 and 3 Antibody Titers	Titers are presented as GMTs and expressed in terms of the 50 % inhibitory dilution.	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	Number of Subjects With Anti-pneumococcal Antibody Concentrations Greater Than or Equal to Pre-defined Cut-off Values	Pneumococcal antibodies assessed included anti-4, anti-6B, anti-9V, anti-14, anti-18C, anti-19F and anti-23F antibodies. The cut-off values assessed were 0.05 and 0.2 micrograms per milliliter (µg/mL).	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	Anti-pneumococcal Antibody Concentrations	Pneumococcal antibodies assessed included anti-4, anti-6B, anti-9V, anti-14, anti-18C, anti-19F and anti-23F antibodies. Concentrations are presented as GMCs and expressed as micrograms per milliliter (µg/mL).	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	Number of Subjects Reporting Solicited Local and General Symptoms During the Primary Vaccination Course	Solicited local symptoms assessed include pain, redness and swelling at the injection site. Solicited general symptoms assessed include drowsiness, irritability, loss of appetite and fever (rectal temperature greater than or equal to 38 degrees Celcius).	During the 8-Day (Day 0-7) follow-up period after any vaccine dose during the primary vaccination course
Secondary	Number of Subjects Reporting Solicited Local and General Symptoms After Administration of the Polysaccharide Challenge Dose	Solicited local symptoms assessed include pain, redness and swelling at the injection site. Solicited general symptoms assessed include drowsiness, irritability, loss of appetite and fever (rectal temperature greater than or equal to 38 degrees Celcius).	During the 8-Day (Day 0-7) follow-up period after the polysaccharide challenge dose
Secondary	Number of Subjects Reporting Unsolicited Adverse Events During the Primary Vaccination Course	Unsolicited adverse event covers any adverse event 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 after any vaccine dose during the primary vaccination course
Secondary	Number of Subjects Reporting Unsolicited Adverse Events After Administration of the Polysaccharide Challenge Dose	Unsolicited adverse event covers any adverse event 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 after administration of the polysaccharide challenge dose
Secondary	Number of Subjects Reporting Serious Adverse Events During the Primary Vaccination Course	Serious adverse events cover all 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.	Up to one month after the 3-dose primary vaccination course (Month 5)
Secondary	Number of Subjects Reporting Serious Adverse Events After Administration of the Polysaccharide Challenge Dose	Serious adverse events cover all 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.	Up to one month following administration of the polysaccharide challenge dose (Month 11)

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