Neisseria MeningitidisPhase 3NCT01978093

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

A Phase 3 study testing Hib-MenCY-TT (MenHibrix®), Pediarix® and Rotarix® in people with Neisseria Meningitidis and Haemophilus Influenzae Type b, run by GlaxoSmithKline at 26 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 6 to 12 weeksHealthy volunteers can take part
Conditions the study is for: Neisseria Meningitidis, Haemophilus Influenzae Type b
What is being tested?: Hib-MenCY-TT (MenHibrix®), Pediarix® and Rotarix®
Type of treatment: Vaccines, Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 600 participants
Where: 26 sitesUnited States
Study dates: 1 Feb 2014to 18 Mar 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 12 weeks
All sexes
Healthy volunteers accepted
Child

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

26 sites in 1 country.

City, postcode or hospital

26 sites in 1 country

United States26 sites

GSK Investigational Site
Birmingham, Alabama, 35205
GSK Investigational Site
Charleston, South Carolina, 29406
GSK Investigational Site
Cleveland, Ohio, 44121
GSK Investigational Site
Dayton, Ohio, 45406
GSK Investigational Site
Fall River, Massachusetts, 02721
GSK Investigational Site
Fayetteville, Arkansas, 72703
GSK Investigational Site
Fresno, California, 93726
GSK Investigational Site
Hermitage, Pennsylvania, 16148
GSK Investigational Site
Huntington Beach, California, 92648
GSK Investigational Site
Jonesboro, Arkansas, 72401
GSK Investigational Site
Layton, Utah, 84041
GSK Investigational Site
Murray, Utah, 84124
GSK Investigational Site
Niles, Michigan, 49120
GSK Investigational Site
Orem, Utah, 84057
GSK Investigational Site
Paramount, California, 90723
GSK Investigational Site
Pleasanton, California, 94588
GSK Investigational Site
Raleigh, North Carolina, 27609
GSK Investigational Site
Roseville, California, 95661
GSK Investigational Site
Roy, Utah, 84067
GSK Investigational Site
Sacramento, California, 95823
GSK Investigational Site
San Jose, California, 95119
GSK Investigational Site
Santa Clara, California, 95051
GSK Investigational Site
Stevensville, Michigan, 49127
GSK Investigational Site
Syracuse, Utah, 84075
GSK Investigational Site
Walnut Creek, California, 94596
GSK Investigational Site
Woburn, Massachusetts, 01801

Other trials in United States

About this study

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

Conditions: Neisseria Meningitidis, Haemophilus Influenzae Type b
Being tested: Hib-MenCY-TT (MenHibrix®), Pediarix®, Rotarix®, Prevnar 13®, PedvaxHIB®
Keywords: Conjugate, Immunogenicity, Hib-MenCY-TT vaccine, Haemophilus type b, Safety, Reactogenicity
Medical subject headings: Haemophilus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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.
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.
Rotarix®Biological
2 doses administered orally at Day 0 and Month 2 each in the HibCY Group and 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.
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.
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.

Study groups in NCT01978093
Study group	Role	What they receive
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. Receives: 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. Receives: Biological: Pediarix®; Biological: Rotarix®; Biological: Prevnar 13®; Biological: PedvaxHIB®; Biological: Havrix®

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
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.
Measured: 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.
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.
Measured: 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
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.
Measured: 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.
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.
Measured: 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
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.
Measured: 1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14).
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.
Measured: 2 month post-dose 2 of Rotarix (Month 4)
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.
Measured: 1 month post-dose 1 of Havrix (Month 11-14)
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
Measured: 1 month post-dose 1 of HAV (M11-14).
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
Measured: 1 month post-dose 2 of HAV (Month 17-20).
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
Measured: 1 month post-dose 3 (Month 5) and 1 month post-dose 4 (Month 11-14)
Percentage of Subjects Reporting Any Solicited Local Adverse Events (AE).
Solicited local adverse events include pain, redness and swelling at injection site.
Measured: 4 days (Day 0 to Day 3) after all vaccines post-primary and post-fourth dose
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.
Measured: 4 days (Day 0 to Day 3) after all vaccines post-primary and post-fourth dose.
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.
Measured: During 31 days (Day 0 to Day 30) after all vaccines post-primary (Dose 1-3) and post-fourth dose (Dose 4)
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.
Measured: During the entire study period (from Day 0 to Month 17-20)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Feb 201418 Mar 2016

First posted7 Nov 2013 (estimated)
Study start1 Feb 2014
Primary completion18 Mar 2016
Study completion18 Mar 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Neisseria MeningitidisStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 600 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01978093
Sponsor's protocol ID: 112931
Other IDs: 2013-003459-39
Status last verified: Aug 2018
First submitted: 31 Oct 2013
Last updated: 14 Sep 2018
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01978093
Acronym / sponsor ID: 112931
Conditions: Neisseria Meningitidis, Haemophilus Influenzae Type b
Keywords: Conjugate, Immunogenicity, Hib-MenCY-TT vaccine, Haemophilus type b, Safety, Reactogenicity
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 600 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 1 Feb 2014
Primary completion: 18 Mar 2016 (actual)
Study completion: 18 Mar 2016 (actual)
First posted: 7 Nov 2013 (estimated)
Results: Posted 26 Jun 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
HibCY Group	Experimental	Biological: Hib-MenCY-TT (MenHibrix®), Biological: Pediarix®, Biological: Rotarix®, Biological: Prevnar 13®, Biological: Havrix®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.
PedHIB Group	Active comparator	Biological: Pediarix®, Biological: Rotarix®, Biological: Prevnar 13®, Biological: PedvaxHIB®, Biological: Havrix®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.

Who may qualify

Ages: 6 to 12 weeks
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (6 listed)

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).

Key exclusion criteria (13 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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	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.	Biological	HibCY Group, PedHIB Group
Rotarix®2 doses administered orally at Day 0 and Month 2 each in the HibCY Group and PedHIB Group.	Biological	HibCY Group, 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.	Biological	HibCY Group, 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.	Biological	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.	Biological	HibCY Group, PedHIB Group

Primary outcome

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.
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
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.
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
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

14 secondary outcomes

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)]
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)]
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)].
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).
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).
Percentage of Subjects With Anti-rotavirus IgA Antibody Concentrations ≥ 20 Units (U)/mL
Time frame: 2 month post-dose 2 of Rotarix (Month 4)
Percentage of Subjects With Anti-HAV Antibodies ≥ 15 mIU/mL
Time frame: 1 month post-dose 1 of Havrix (Month 11-14)
Anti-HAV GMCs ≥ 15 mIU/mL
Time frame: 1 month post-dose 1 of HAV (M11-14).
GMCs for Anti-HAV Antibodies ≥15mIU/mL.
Time frame: 1 month post-dose 2 of HAV (Month 17-20).
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)
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
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.
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)
Percentage of Subjects Reporting Any Serious Adverse Events (SAEs).
Time frame: During the entire study period (from Day 0 to Month 17-20)

Results and safety

Results posted to the registry on 26 Jun 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
HibCY Group	297	232
PedHIB Group	303	230

Primary outcome: 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]. Number (95% Confidence Interval). Unit: Percentage of subjects

Measure	HibCY Group n = 223	PedHIB Group n = 218
Value	98.2 (95.5 to 99.5)	97.2 (94.1 to 99.0)

HibCY Group vs PedHIB Group: Difference in percentage of subjects: 0.96 (95% CI -2.12 to 4.30), Group difference in proportions

Population analysed: The analysis was performed on the Fourth dose According to Protocol (ATP) cohort for analysis of immunogenicity, which included all evaluable subjects who have received 3 vaccine doses in the first 3-doses vaccination course and who have received the fourth vaccine dose and the first Havrix dose.

Primary outcome: Anti-rotavirus Serum Immunoglobulin A (IgA) Geometric Mean Concentrations (GMCs).

Time frame: 2 months post-dose 2 of Rotarix (Month 4). Geometric mean (95% Confidence Interval). Unit: U/mL

Measure	HibCY Group n = 155	PedHIB Group n = 161
Value	138.9 (104.0 to 185.5)	115.0 (87.5 to 151.0)

HibCY Group vs PedHIB Group: Adjusted GMC ratios: 1.21 (97.5% CI 0.77 to 1.90), ANCOVA

Population analysed: The analysis was performed on the Rota ATP cohort for analysis of immunogenicity, which included all evaluable subjects who received the two doses of Rotarix vaccine and for whom immunogenicity results were available.

Primary outcome: Anti-Streptococcus (S) Pneumoniae GMCs

Time frame: 1 month post-dose 3 of Prevnar 13 (Month 5). Geometric mean (95% Confidence Interval). Unit: µg/mL

Measure	HibCY Group n = 156	PedHIB Group n = 158
Anti-1 antibody	1.49 (1.30 to 1.70)	1.26 (1.10 to 1.44)
Anti-3 antibody	0.55 (0.48 to 0.63)	0.48 (0.42 to 0.55)
Anti-4 antibody	0.81 (0.72 to 0.90)	0.74 (0.66 to 0.84)
Anti-5 antibody	0.80 (0.71 to 0.91)	0.68 (0.59 to 0.78)
Anti-6A antibody	1.76 (1.55 to 2.00)	1.37 (1.18 to 1.60)
Anti-6B antibody	1.00 (0.85 to 1.18)	0.87 (0.73 to 1.05)
Anti-7F antibody	2.59 (2.29 to 2.93)	2.36 (2.10 to 2.65)
Anti-9V antibody	0.78 (0.69 to 0.89)	0.63 (0.55 to 0.73)

HibCY Group vs PedHIB Group: Adjusted GMC ratio: 1.18 (97.5% CI 0.95 to 1.47), ANCOVA
HibCY Group vs PedHIB Group: Adjusted GMC ratio: 1.15 (97.5% CI 0.93 to 1.42), ANCOVA
HibCY Group vs PedHIB Group: Adjusted GMC ratio: 1.08 (97.5% CI 0.90 to 1.31), ANCOVA

Population analysed: The analysis was performed on the First three doses ATP cohort for analysis of immunogenicity, which included all evaluable subjects who have received three doses of Prevnar 13 vaccine and for whom immunogenicity results were available.

Primary outcome: 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). Number (95% Confidence Interval). Unit: Percentage of subjects

Measure	HibCY Group n = 129	PedHIB Group n = 124
Value	100 (97.2 to 100)	100 (97.1 to 100)

HibCY Group vs PedHIB Group: Difference in percentage of subjects: 0.00 (97.5% CI -3.76 to 3.91), Group difference in proportions

Population analysed: The analysis was performed on the Havrix ATP cohort for analysis of immunogenicity which include all evaluable subjects who received two doses of Havrix vaccine and for whom immunogenicity results were available.

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited adverse events - Day 0-Day 4 Unsolicited Adverse events - Day 0- Day 31 after all vaccines post-primary and post-fourth dose. SAEs - day 0 to study end (Month 17-20). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HibCY Group	8 of 297 (2.7%)	282 of 297 (94.9%)	1 of 297
PedHIB Group	11 of 303 (3.6%)	291 of 303 (96%)	0 of 303

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

26 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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]). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01978093.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2018.