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

• ClinicalTrials.gov Identifier: NCT01978093
• Recruitment Status: Completed
• First Posted: November 7, 2013
• Results First Posted: June 26, 2018
• Last Update Posted: September 14, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Neisseria Meningitidis; Haemophilus Influenzae Type b	Biological: Hib-MenCY-TT (MenHibrix®); Biological: Pediarix®; Biological: Rotarix®; Biological: Prevnar 13®; Biological: PedvaxHIB®; Biological: Havrix®	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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
• Study Start Date: February 1, 2014
• Actual Primary Completion Date: March 18, 2016
• Actual Study Completion Date: March 18, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: HibCY Group; Subjects received 4 doses of Hib-MenCY-TT (MenHibrix®) vaccine at Day 0, Month 2, Month 4 and Month 10-13 , 3 doses of Pediarix® vaccine at Day 0, Month 2 and Month 4, 2 doses of Rotarix® vaccine at Day 0 and Month 2, 4 doses of Prevnar 13® vaccine at Day 0 and Month 2, Month 4 and Month 10-13 and 2 doses of Havrix® vaccine at Month 10-13 and Month 16-19.	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.; Biological: 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.; Biological: Rotarix®; 2 doses administered orally at Day 0 and Month 2 each in the HibCY Group and PedHIB Group.; Biological: 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.; Biological: 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.
Active Comparator: PedHIB Group; Subjects received 3 doses of PedvaxHIB® vaccine at Day 0, Month 2 and Month 10-13, 3 doses of Pediarix® vaccine at Day 0, Month 2 and Month 4, 2 doses of Rotarix® vaccine at Day 0 and Month 2, 4 doses of Prevnar 13® vaccine at Day 0 and Month 2, Month 4 and Month 10-13 and 2 doses of Havrix® vaccine at Month 10-13 and Month 16-19.	Biological: 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.; Biological: Rotarix®; 2 doses administered orally at Day 0 and Month 2 each in the HibCY Group and PedHIB Group.; Biological: 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.; Biological: PedvaxHIB®; 3 doses administered IM in the right upper anterolateral thigh at Day 0, Month 2 and Month 10-13 in the PedHIB Group.; Biological: 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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Subjects With Anti-Polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (≥) 1.0 µg/mL [ Time Frame: 1 month after the fourth dose for HibCY Group and 1 month after third dose for PedHIB Group [Month (M) 11-14] ]

   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.

2. Anti-rotavirus Serum Immunoglobulin A (IgA) Geometric Mean Concentrations (GMCs). [ Time Frame: 2 months post-dose 2 of Rotarix (Month 4) ]

   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

3. Anti-Streptococcus (S) Pneumoniae GMCs [ Time Frame: 1 month post-dose 3 of Prevnar 13 (Month 5) ]

   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.

4. Percentage of Subjects With Anti-Hepatitis A (Anti-Havrix) Antibody Concentrations ≥ 15mIU/mL [ Time Frame: 1 month post-dose 2 of Havrix (Month 17-20) ]

   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

5. Anti-S. Pneumoniae GMCs [ Time Frame: 1 month post-dose 4 of Prevnar 13 (Month 11-14) ]

   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

Secondary Outcome Measures :

1. Percentage of Subjects With Anti-PRP Antibody Concentrations ≥0.15 µg/mL. [ Time Frame: 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)] ]
   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. Anti-PRP GMCs≥ 0.15 µg/mL. [ Time Frame: 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)] ]

   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.

3. Percentage of Subjects With Anti-PRP Antibody Concentrations ≥1.0 µg/mL [ Time Frame: 2 months post-dose 2 [PedHib group only (Month 4)] and 1 month postdose 3 [HibCY group only (Month 5)]. ]
   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.
4. 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. [ Time Frame: 1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14). ]
   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.
5. Geometric Mean Titres (GMTs) of Human Complement Serum Bactericidal Assay to N. Meningitidis Serogroup C (hSBA-MenC) and to hSBA-MenY [ Time Frame: 1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14). ]
   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.
6. Percentage of Subjects With Anti-rotavirus IgA Antibody Concentrations ≥ 20 Units (U)/mL [ Time Frame: 2 month post-dose 2 of Rotarix (Month 4) ]
   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.
7. Percentage of Subjects With Anti-HAV Antibodies ≥ 15 mIU/mL [ Time Frame: 1 month post-dose 1 of Havrix (Month 11-14) ]
   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.
8. Anti-HAV GMCs ≥ 15 mIU/mL [ Time Frame: 1 month post-dose 1 of HAV (M11-14). ]
   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
9. GMCs for Anti-HAV Antibodies ≥15mIU/mL. [ Time Frame: 1 month post-dose 2 of HAV (Month 17-20). ]
   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
10. 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 [ Time Frame: 1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14) ]
    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
11. Percentage of Subjects Reporting Any Solicited Local Adverse Events (AE). [ Time Frame: 4 days (Day 0 to Day 3) after all vaccines post-primary and post-fourth dose ]
    Solicited local adverse events include pain, redness and swelling at injection site.
12. Percentage of Subjects Reporting Any Solicited General AEs. [ Time Frame: 4 days (Day 0 to Day 3) after all vaccines post-primary and post-fourth dose. ]
    Solicited general AEs include fever [defined as temperature ≥38.0 degrees Celsius (°C) by any method], drowsiness, irritability/fussiness and loss of appetite.
13. Percentage of Subjects Reporting Any Unsolicited AEs. [ Time Frame: During 31 days (Day 0 to Day 30) after all vaccines post-primary (Dose 1-3) and post-fourth dose (Dose 4) ]
    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.
14. Percentage of Subjects Reporting Any Serious Adverse Events (SAEs). [ Time Frame: During the entire study period (from Day 0 to Month 17-20) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 6 Weeks to 12 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Birmingham, Alabama, United States, 35205

United States, Arkansas

GSK Investigational Site

Fayetteville, Arkansas, United States, 72703

GSK Investigational Site

Jonesboro, Arkansas, United States, 72401

United States, California

GSK Investigational Site

Fresno, California, United States, 93726

GSK Investigational Site

Huntington Beach, California, United States, 92648

GSK Investigational Site

Paramount, California, United States, 90723

GSK Investigational Site

Pleasanton, California, United States, 94588

GSK Investigational Site

Roseville, California, United States, 95661

GSK Investigational Site

Sacramento, California, United States, 95823

GSK Investigational Site

San Jose, California, United States, 95119

GSK Investigational Site

Santa Clara, California, United States, 95051

GSK Investigational Site

Walnut Creek, California, United States, 94596

United States, Massachusetts

GSK Investigational Site

Fall River, Massachusetts, United States, 02721

GSK Investigational Site

Woburn, Massachusetts, United States, 01801

United States, Michigan

GSK Investigational Site

Niles, Michigan, United States, 49120

GSK Investigational Site

Stevensville, Michigan, United States, 49127

United States, North Carolina

GSK Investigational Site

Raleigh, North Carolina, United States, 27609

United States, Ohio

GSK Investigational Site

Cleveland, Ohio, United States, 44121

GSK Investigational Site

Dayton, Ohio, United States, 45406

United States, Pennsylvania

GSK Investigational Site

Hermitage, Pennsylvania, United States, 16148

United States, South Carolina

GSK Investigational Site

Charleston, South Carolina, United States, 29406

United States, Utah

GSK Investigational Site

Layton, Utah, United States, 84041

GSK Investigational Site

Murray, Utah, United States, 84124

GSK Investigational Site

Orem, Utah, United States, 84057

GSK Investigational Site

Roy, Utah, United States, 84067

GSK Investigational Site

Syracuse, Utah, United States, 84075

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01978093
• Other Study ID Numbers: 112931; 2013-003459-39 ( EudraCT Number )
• First Posted: November 7, 2013
• Results First Posted: June 26, 2018
• Last Update Posted: September 14, 2018
• Last Verified: August 2018

Keywords provided by GlaxoSmithKline:

Conjugate; Immunogenicity; Hib-MenCY-TT vaccine; Haemophilus type b; Safety; Reactogenicity

Additional relevant MeSH terms:

Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs