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

NCT01978093 | Completed Phase 3 Results

• 2 other identifiers: 1129312013-003459-39
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 26

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.

Conditions

Neisseria Meningitidis; Haemophilus Influenzae Type b

Keywords

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

Outcome Measures

Primary Outcomes (5)

• 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]

• 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)

• 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)

• 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)

• 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 Outcomes (14)

• Percentage of Subjects With Anti-PRP Antibody Concentrations ≥0.15 µg/mL.

  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)]

• Anti-PRP GMCs≥ 0.15 µg/mL.

  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)]

• Percentage of Subjects With Anti-PRP Antibody Concentrations ≥1.0 µg/mL

  2 months post-dose 2 [PedHib group only (Month 4)] and 1 month postdose 3 [HibCY group only (Month 5)].

• 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.

  1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14).

• Geometric Mean Titres (GMTs) of Human Complement Serum Bactericidal Assay to N. Meningitidis Serogroup C (hSBA-MenC) and to hSBA-MenY

  1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14).

Study Arms (2)

HibCY Group

EXPERIMENTAL

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®); Biological: Pediarix®; Biological: Rotarix®; Biological: Prevnar 13®; Biological: Havrix®

PedHIB Group

ACTIVE COMPARATOR

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®; Biological: Rotarix®; Biological: Prevnar 13®; Biological: PedvaxHIB®; Biological: Havrix®

Interventions

Hib-MenCY-TT (MenHibrix®) BIOLOGICAL

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.

HibCY Group

Pediarix® BIOLOGICAL

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.

HibCY Group; PedHIB Group

Rotarix® BIOLOGICAL

2 doses administered orally at Day 0 and Month 2 each in the HibCY Group and PedHIB Group.

HibCY Group; PedHIB Group

Prevnar 13® BIOLOGICAL

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.

HibCY Group; PedHIB Group

PedvaxHIB® BIOLOGICAL

3 doses administered IM in the right upper anterolateral thigh at Day 0, Month 2 and Month 10-13 in the PedHIB Group.

PedHIB Group

Havrix® BIOLOGICAL

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.

HibCY Group; PedHIB Group

Eligibility Criteria

• Age: 6 Weeks - 12 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (26)

GSK Investigational Site

Birmingham, Alabama, 35205, United States

Location

GSK Investigational Site

Fayetteville, Arkansas, 72703, United States

Location

GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

Location

GSK Investigational Site

Fresno, California, 93726, United States

Location

GSK Investigational Site

Huntington Beach, California, 92648, United States

Location

GSK Investigational Site

Paramount, California, 90723, United States

Location

GSK Investigational Site

Pleasanton, California, 94588, United States

Location

GSK Investigational Site

Roseville, California, 95661, United States

Location

GSK Investigational Site

Sacramento, California, 95823, United States

Location

GSK Investigational Site

San Jose, California, 95119, United States

Location

GSK Investigational Site

Santa Clara, California, 95051, United States

Location

GSK Investigational Site

Walnut Creek, California, 94596, United States

Location

GSK Investigational Site

Fall River, Massachusetts, 02721, United States

Location

GSK Investigational Site

Woburn, Massachusetts, 01801, United States

Location

GSK Investigational Site

Niles, Michigan, 49120, United States

Location

GSK Investigational Site

Stevensville, Michigan, 49127, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27609, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44121, United States

Location

GSK Investigational Site

Dayton, Ohio, 45406, United States

Location

GSK Investigational Site

Hermitage, Pennsylvania, 16148, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29406, United States

Location

GSK Investigational Site

Layton, Utah, 84041, United States

Location

GSK Investigational Site

Murray, Utah, 84124, United States

Location

GSK Investigational Site

Orem, Utah, 84057, United States

Location

GSK Investigational Site

Roy, Utah, 84067, United States

Location

GSK Investigational Site

Syracuse, Utah, 84075, United States

Location

MeSH Terms

Conditions

Haemophilus Infections

Interventions

Hib-MenCY-TT vaccine; PEDIARIX; RIX4414 vaccine; 13-valent pneumococcal vaccine; Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; Hepatitis A Vaccines

Condition Hierarchy (Ancestors)

Pasteurellaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 7, 2013
• Study Start: February 1, 2014
• Primary Completion: March 18, 2016
• Study Completion: March 18, 2016
• Last Updated: September 14, 2018
• Results First Posted: June 26, 2018

Record last verified: 2018-08

Locations

US (26)