Immunogenicity, Safety and Reactogenicity Study of GlaxoSmithKline (GSK) Biologicals' Hib-MenCY-TT (MenHibrix®) Vaccine Compared to Merck & Co, Inc. PedvaxHIB Vaccine in Healthy Infants and Toddlers 12 to 15 Months of Age

Haemophilus Influenzae Type b Clinical Trial

Official title:

Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Hib-MenCY-TT (MenHibrix®) Vaccine 792014 Compared to Merck & Co, Inc. Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) Vaccine in Healthy Infants and Toddlers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01978093
• Other study ID #: 112931
• Secondary ID: 2013-003459-39
• Status: Completed
• Phase: Phase 3
• Start date: February 1, 2014
• Est. completion date: March 18, 2016

Study information

• Verified date: August 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of GSK Biologicals' Hib-MenCY-TT (MenHibrix®) vaccine co-administered with Rotarix, Prevnar 13 and Havrix as compared to PedvaxHIB co-administered with Rotarix, Prevnar 13 and Havrix in infants and toddlers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: March 18, 2016
• Est. primary completion date: March 18, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 12 Weeks

Eligibility

Inclusion Criteria:

• Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.

• 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(s)/LAR(s) of the subject.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

• Born full-term (i.e. born after a gestation period of at least 37 weeks inclusive).

• Infants who have not received a previous dose of hepatitis B vaccine or those who have received only 1 dose of hepatitis B vaccine administered at least 30 days prior to enrollment.

Exclusion Criteria:

• Child in care.

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine or planned use during the study period.

• Chronic administration of immunosuppressants or other immune-modifying drugs since birth prior to the first vaccine dose. Inhaled and topical steroids are allowed.

• Previous vaccination against Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, rotavirus, pneumococcus, hepatitis A and/or poliovirus; more than one previous dose of hepatitis B vaccine.

• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after the dose of vaccines. Subjects may receive inactivated influenza vaccine or pandemic influenza vaccines any time during the study according to the national recommendation. Measles, mumps, rubella and varicella vaccination are allowed 30 days before or 30 days after the final vaccination of Hib-MenCY-TT or PedvaxHIB.

• History of Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, pneumococcus, hepatitis B, hepatitis A, rotavirus, and/or poliovirus 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 vaccines, including dry natural latex rubber. Hypersensitivity to any component of the vaccines, including gelatin or neomycin.

• Major congenital defects or serious chronic illnesses.

• History of any neurologic disorders or seizures. A single, simple febrile seizure is allowed.

• Subjects with history of intussusceptions or uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusceptions.

• Acute disease and/or fever at the time of enrollment.

• Administration of immunoglobulins and/or blood products since birth or planned administration during the study period.

Related Conditions & MeSH terms

• Haemophilus Influenzae Type b
• Neisseria Meningitidis

Intervention

Biological:
• Hib-MenCY-TT (MenHibrix®)
4 doses administered intramuscularly (IM) in the right upper anterolateral thigh at Day 0, Month 2, Month 4 and Month 10-13 in the HibCY Group.
• Pediarix®
3 doses administered IM in the left upper anterolateral thigh at Day 0, Month 2 and Month 4. 2 doses administered IM in the left upper anterolateral thigh at Day 0 and Month 2 and 1 dose administered IM in the right upper anterolateral thigh at Month 4 in the PedHIB Group.
• Rotarix®
2 doses administered orally at Day 0 and Month 2 each in the HibCY Group and PedHIB Group.
• Prevnar 13®
4 doses administered IM in the left lower anterolateral thigh at Day 0, Month 2, Month 4 and Month 10-13 each in the HibCY Group and PedHIB Group.
• PedvaxHIB®
3 doses administered IM in the right upper anterolateral thigh at Day 0, Month 2 and Month 10-13 in the PedHIB Group.
• Havrix®
2 doses administered IM in the left upper anterolateral thigh at Month 10-13 and Month 16-19 each in the HibCY Group and PedHIB Group.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Fall River	Massachusetts
United States	GSK Investigational Site	Fayetteville	Arkansas
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Hermitage	Pennsylvania
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Layton	Utah
United States	GSK Investigational Site	Murray	Utah
United States	GSK Investigational Site	Niles	Michigan
United States	GSK Investigational Site	Orem	Utah
United States	GSK Investigational Site	Paramount	California
United States	GSK Investigational Site	Pleasanton	California
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Roseville	California
United States	GSK Investigational Site	Roy	Utah
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	Santa Clara	California
United States	GSK Investigational Site	Stevensville	Michigan
United States	GSK Investigational Site	Syracuse	Utah
United States	GSK Investigational Site	Walnut Creek	California
United States	GSK Investigational Site	Woburn	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Anti-Polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (=) 1.0 µg/mL	Percentage of subjects with Anti-PRP antibody concentrations=1.0 µg/mL were assessed.; Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts. Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.As per an hierarchical procedure, the primary objective about Anti-PRP will first need to be met to be able to conclude on any other primary objective, and within each subsequent arm, the first primary objective will have to be reached to conclude on the second primary objective of that Epoch.	1 month after the fourth dose for HibCY Group and 1 month after third dose for PedHIB Group [Month (M) 11-14]
Primary	Anti-rotavirus Serum Immunoglobulin A (IgA) Geometric Mean Concentrations (GMCs).	Anti-rotavirus serum IgA was assessed by ELISA, tabulated as GMCs and expressed in Units per mililiter (U/mL).Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.; Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.As per a hierarchical procedure, the primary objective about Anti-PRP will first need to be met to be able to conclude on any other primary objective, and within each subsequent arm, the first primary objective will have to be reached to conclude on the second primary objective of that Epoch	2 months post-dose 2 of Rotarix (Month 4)
Primary	Anti-Streptococcus (S) Pneumoniae GMCs	Antibody concentrations against S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F were assessed by ELISA, tabulated as GMCs and expressed in µg/mL.; Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.As per an hierarchical procedure, the primary objective about Anti-PRP will first need to be met to be able to conclude on any other primary objective, and within each subsequent arm, the first primary objective will have to be reached to conclude on the second primary objective of that Epoch.	1 month post-dose 3 of Prevnar 13 (Month 5)
Primary	Percentage of Subjects With Anti-Hepatitis A (Anti-Havrix) Antibody Concentrations = 15mIU/mL	Percentage of subjects with Anti-Havrix (Anti-HAV) antibody concentrations was assessed. The cut-off value is =15 mIU/mL.; Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.As per an hierarchical procedure, the primary objective about Anti-PRP will first need to be met to be able to conclude on any other primary objective, and within each subsequent arm, the first primary objective will have to be reached to conclude on the second primary objective of that Epoch	1 month post-dose 2 of Havrix (Month 17-20)
Primary	Anti-S. Pneumoniae GMCs	Antibody concentrations against S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F were assessed by ELISA, tabulated as GMCs and expressed in µg/mL.; Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.As per an hierarchical procedure, the primary objective about Anti-PRP will first need to be met to be able to conclude on any other primary objective, and within each subsequent arm, the first primary objective will have to be reached to conclude on the second primary objective of that Epoch	1 month post-dose 4 of Prevnar 13 (Month 11-14)
Secondary	Percentage of Subjects With Anti-PRP Antibody Concentrations =0.15 µg/mL.	The cut-off value for this assay was 0.15 µg/mL. Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.	2 months post-dose 2 [PedHib Group only (Month 4)], 1 month post-dose 3 (Month 5 for HibCY group and Months 11-14 for PedHib Group) and 1 month post-dose 4 [HibCY Group only (Month 11-14)]
Secondary	Anti-PRP GMCs= 0.15 µg/mL.	Anti-PRP antibody concentrations were assessed by Enzyme-Linked-Immunosorbent-Assay (ELISA), tabulated as Geometric Mean Concentrations (GMCs) and expressed in micrograms per mililiter (µg/mL).The cut-off value for this assay was 0.15 µg/mL.; Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.	2 months post-dose 2 [PedHib Group only (Month 4)], 1 month post-dose 3 (Month 5 for HibCY group and Month 11-14 for PedHib Group) and 1 month post-dose 4 [HibCY Group only (Month 11-14)]
Secondary	Percentage of Subjects With Anti-PRP Antibody Concentrations =1.0 µg/mL	The cut-off value for this assay was 1.0 µg/mL. Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.	2 months post-dose 2 [PedHib group only (Month 4)] and 1 month postdose 3 [HibCY group only (Month 5)].
Secondary	Percentage of Subjects With Serum Bactericidal Assay to N. Meningitidis Serogroup C (hSBA-MenC) and N. Meningitidis Serogroup Y (hSBA-MenY) Antibody Titers =1:8, =1:16, =1:32.	The cut off values are dilutions of 1:8, 1:16 and 1:32. Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.	1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14).
Secondary	Geometric Mean Titres (GMTs) of Human Complement Serum Bactericidal Assay to N. Meningitidis Serogroup C (hSBA-MenC) and to hSBA-MenY	The cut-off values are dilutions of 1:8, 1:16 and 1:32. Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.	1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14).
Secondary	Percentage of Subjects With Anti-rotavirus IgA Antibody Concentrations = 20 Units (U)/mL	The cut-off value is 20 Units (U)/mL Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.	2 month post-dose 2 of Rotarix (Month 4)
Secondary	Percentage of Subjects With Anti-HAV Antibodies = 15 mIU/mL	The cut-off value is 15 mIU/mL. Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups.	1 month post-dose 1 of Havrix (Month 11-14)
Secondary	Anti-HAV GMCs = 15 mIU/mL	The cut-off value is 15 mIU/mL. Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups	1 month post-dose 1 of HAV (M11-14).
Secondary	GMCs for Anti-HAV Antibodies =15mIU/mL.	The cut-off value is 15 mIU/mL. Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups	1 month post-dose 2 of HAV (Month 17-20).
Secondary	Percentage of Subjects With S. Pneumoniae Antibody Concentrations = 0.15 µg/mL, = 0.26 µg/mL and = 0.35 µg/mL for Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F	The cut-off values are 0.15, 0.26, 0.35 µg/mL. Analysis of Immunogenicity is performed on blood sample (BS) sub-cohorts.Assignment to a BS sub-cohort depends on the date of enrolment of the subject: BS sub-cohort for the first 200 , for the next 200 subjects or for the last 200 subjects. Within each BS sub-cohort subjects have been randomized 1:1 to either HibCY or PedHIB groups	1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14)
Secondary	Percentage of Subjects Reporting Any Solicited Local Adverse Events (AE).	Solicited local adverse events include pain, redness and swelling at injection site.	4 days (Day 0 to Day 3) after all vaccines post-primary and post-fourth dose
Secondary	Percentage of Subjects Reporting Any Solicited General AEs.	Solicited general AEs include fever [defined as temperature =38.0 degrees Celsius (°C) by any method], drowsiness, irritability/fussiness and loss of appetite.	4 days (Day 0 to Day 3) after all vaccines post-primary and post-fourth dose.
Secondary	Percentage of Subjects Reporting Any Unsolicited AEs.	Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms were reported as an unsolicited adverse event.	During 31 days (Day 0 to Day 30) after all vaccines post-primary (Dose 1-3) and post-fourth dose (Dose 4)
Secondary	Percentage of Subjects Reporting Any Serious Adverse Events (SAEs).	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the entire study period (from Day 0 to Month 17-20)