Safety and Immunogenicity Study of Hib-MenCY-TT Vaccine Compared to Licensed Hib Conjugate Vaccine - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00289783

Purpose

This study evaluates the immunogenicity and consistency of 3 Hib-MenCY-TT vaccine lots and the safety and immunogenicity of Hib-MenCY-TT vaccine compared to a control group receiving licensed Hib conjugate vaccine, when each are co-administered with Pediarix® to healthy infants at 2, 4, and 6 months of age. The study will also evaluate the safety and immunogenicity of Hib-MenCY-TT vaccine compared to a control group receiving licensed Hib conjugate vaccine, when each are co-administered with M-M-R® II and Varivax® at 12 to 15 months of age.

Condition	Intervention	Phase
Haemophilus Influenzae Type b Infection Meningococcal Infection	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine Biological: ActHIB Biological: PedvaxHIB Biological: Prevnar Biological: M-M-R II Biological: Pediarix Biological: Varivax	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Safety/Efficacy Study
Official Title:	Immunogenicity Study to Evaluate 3 Hib-MenCY-TT Vaccine Lots & GSK Biologicals' Hib & N. Meningitidis Serogroups C&Y-Tetanus Toxoid Conjugate Vaccine Combined vs Monovalent Hib Vaccine in Healthy Infants at 2, 4, 6 & 12 to 15 Months

Resource links provided by NLM:

MedlinePlus related topics: Chickenpox Diphtheria Fever Flu Measles Mumps Rubella Shingles Tetanus

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Anti-PRP antibody concentrations [ Time Frame: 1 month after the primary vaccination course and post-booster vaccination. ] [ Designated as safety issue: No ]
hSBA-MenC titres [ Time Frame: 1 month after the primary vaccination course and post-booster vaccination ] [ Designated as safety issue: No ]
hSBA-MenY titres [ Time Frame: 1 month after the primary vaccination course and post-booster vaccination ] [ Designated as safety issue: No ]
Anti-diphtheria antibody concentrations [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-tetanus antibody concentrations [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-pertussis toxoid antibody concentrations [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-Filamentous Haemagglutinin antibody concentrations [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-pertactin antibody concentrations [ Time Frame: 1 month after the primary vaccination course. ] [ Designated as safety issue: No ]
Anti-poliovirus 1 antibody titres [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-poliovirus 2 antibody titres [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-poliovirus 3 antibody titres [ Time Frame: 1 month after the primary vaccination course. ] [ Designated as safety issue: No ]
Number of Subjects Reporting Fever > 39.5°C/103.1°F [ Time Frame: In the 4-day follow-up period following any dose of the primary vaccination and following the booster dose. ] [ Designated as safety issue: No ]
Anti-measles antibody concentrations [ Time Frame: Post-booster vaccination ] [ Designated as safety issue: No ]
Anti-mumps antibody titre [ Time Frame: Post-booster vaccination. ] [ Designated as safety issue: No ]
Anti-rubella antibody concentrations [ Time Frame: Post-booster vaccination ] [ Designated as safety issue: No ]
Anti-varicella antibody titres. [ Time Frame: Post-booster vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Anti-PRP antibody concentrations [ Time Frame: 1 month after the primary vaccination course, pre-booster and post-booster vaccination ] [ Designated as safety issue: No ]
rSBA-MenC titres [ Time Frame: 1 month after the primary vaccination course, pre-booster and post-booster vaccination ] [ Designated as safety issue: No ]
rSBA-MenY titres [ Time Frame: 1 month after the primary vaccination course, pre-booster and post-booster vaccination ] [ Designated as safety issue: No ]
Anti-Polysaccharide C antibody concentrations [ Time Frame: 1 month after the primary vaccination course, pre-booster and post-booster vaccination ] [ Designated as safety issue: No ]
Anti-Polysaccharide Y antibody concentrations [ Time Frame: 1 month after the primary vaccination course, pre-booster and post-booster vaccination ] [ Designated as safety issue: No ]
Anti-diphtheria antibody concentrations [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-tetanus antibody concentrations [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-Hepatitis B surface antigen antibody concentrations [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
hSBA-MenY titres [ Time Frame: 1 month after the primary vaccination course, pre-booster and post-booster vaccination ] [ Designated as safety issue: No ]
Anti-pertussis antibody concentrations [ Time Frame: 1 month after the primary vaccination course. ] [ Designated as safety issue: No ]
Anti-poliovirus types 1, 2, and 3 antibody titres. [ Time Frame: 1 month after the primary vaccination course ] [ Designated as safety issue: No ]
Anti-measles antibody concentrations in initially seronegative subjects [ Time Frame: Post-booster vaccination. ] [ Designated as safety issue: No ]
Anti-mumps antibody titres in initially seronegative subjects. [ Time Frame: Post-booster vaccination ] [ Designated as safety issue: No ]
hSBA-MenC titres [ Time Frame: 1 month after the primary vaccination course, pre-booster and post-booster vaccination ] [ Designated as safety issue: No ]
Anti-rubella antibody concentrations in initially seronegative subjects [ Time Frame: Post-booster vaccination ] [ Designated as safety issue: No ]
Anti-varicella antibody titres in initially seronegative subjects. [ Time Frame: Post-booster vaccination. ] [ Designated as safety issue: No ]
Number of subjects reporting Local and General Solicited Adverse Events [ Time Frame: Within 4 days (Day 0 through Day 3) following each vaccine dose. ] [ Designated as safety issue: No ]
Number of subjects reporting unsolicited symptoms [ Time Frame: Within 31 days (Day 0-30) following each dose of vaccine dose ] [ Designated as safety issue: No ]
Number of subjects reporting Serious Adverse Events (SAEs) [ Time Frame: From Dose 0 through 6 months after the last primary dose or until administration of the booster dose (whichever comes first); and from the booster dose of Hib-MenCY-TT vaccine and PedvaxHIB through the end of the 6-month safety follow-up. ] [ Designated as safety issue: No ]
Number of subjects reporting specific adverse events [ Time Frame: From Dose 0 through 6 months after the last primary dose or until administration of the booster dose (whichever comes first); and from the booster dose of Hib-MenCY-TT vaccine and PedvaxHIB through the end of the 6-month safety follow-up. ] [ Designated as safety issue: No ]
% subjects with at least a 4-fold rise in anti-H1N1, anti-H3N2, and anti-B ab titers, measured by hemagglutination inhibition assay (HIA), in subjects who received 1 or 2 doses of flu vaccine within the same flu season concomitantly with study vaccine. [ Time Frame: Post-booster vaccination ] [ Designated as safety issue: No ]
Incidence of increased circumferential swelling at the injected limb(s). [ Time Frame: Within 4 days (Day 0 to Day 3) after booster vaccination ] [ Designated as safety issue: No ]
Incidence of general symptoms specific to measles, mumps, rubella, and varicella vaccination (fever, rash/exanthem, parotid/salivary gland swelling, and any suspected signs of meningism including febrile convulsions). [ Time Frame: Within 43 days (Day 0 through Day 42) after booster vaccination ] [ Designated as safety issue: No ]

Enrollment:	4441
Study Start Date:	February 2006
Study Completion Date:	February 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group A: Experimental Primed with 3 doses of Hib-MenCY-TT vaccine Lot A co-administered with Pediarix. Boosted with 1 dose of Hib-MenCY-TT vaccine, with co-administration of M-M-R II and Varivax to all US subjects in Cohort 1.	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age. Biological: Prevnar 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age. Biological: M-M-R II 1 booster dose by subcutaneous injection at 12 to 15 months of age. Biological: Pediarix 3-dose intramuscular injection at 2, 4 and 6 months of age. Biological: Varivax 1 booster dose by subcutaneous injection at 12 to 15 months of age
Group B: Experimental Primed with 3 doses of Hib-MenCY-TT vaccine Lot B co-administered with Pediarix. Boosted with 1 dose of Hib-MenCY-TT vaccine, with co-administration of M-M-R II and Varivax to all US subjects in Cohort 1	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age. Biological: Prevnar 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age. Biological: M-M-R II 1 booster dose by subcutaneous injection at 12 to 15 months of age. Biological: Pediarix 3-dose intramuscular injection at 2, 4 and 6 months of age. Biological: Varivax 1 booster dose by subcutaneous injection at 12 to 15 months of age
Group C: Experimental Primed with 3 doses of Hib-MenCY-TT vaccine Lot C co-administered with Pediarix. Boosted with 1 dose of Hib-MenCY-TT vaccine, with co-administration of M-M-R II and Varivax to all US subjects in Cohort 1.	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age. Biological: Prevnar 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age. Biological: M-M-R II 1 booster dose by subcutaneous injection at 12 to 15 months of age. Biological: Pediarix 3-dose intramuscular injection at 2, 4 and 6 months of age. Biological: Varivax 1 booster dose by subcutaneous injection at 12 to 15 months of age
Hib Group: Active Comparator Primed with 3 doses of ActHIB co-administered with Pediarix. Boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax to all US subjects in Cohort 1	Biological: ActHIB 3-dose intramuscular injection at 2, 4 and 6 months of age. Biological: PedvaxHIB 1 booster dose by intramuscular injection at 12 to 15 months of age. Biological: Prevnar 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age. Biological: M-M-R II 1 booster dose by subcutaneous injection at 12 to 15 months of age. Biological: Pediarix 3-dose intramuscular injection at 2, 4 and 6 months of age. Biological: Varivax 1 booster dose by subcutaneous injection at 12 to 15 months of age

Detailed Description:

The subjects from this study will participate in one of three cohorts:

US Safety and Immunogenicity (Cohort 1): All immunogenicity analyses in the primary and booster phases will be evaluated in this cohort. These subjects will also contribute to the safety analyses in the primary and booster phases.
Safety Only (Cohort 2): Only safety objectives will be assessed in the primary and booster phases for this cohort.
Non-US Safety and Immunogenicity (Cohort 3): Only descriptive immunogenicity results in the primary and booster phases will be reported for this cohort. These subjects will also contribute to the safety analyses in the primary and booster phases.

Treatment allocation:

Primary phase: Subjects will be randomized with balanced allocation (1:1:1:1) to 1 of the 4 treatment groups and with a stratification according to the cohort. Assignment to a cohort will be based on study site.

Booster phase: Subjects who received Hib-MenCY-TT vaccine in the primary phase will receive a booster dose of Hib-MenCY-TT vaccine. Subjects who received ActHIB in the primary phase will receive a booster dose of PedvaxHIB.

During the 3-dose primary vaccination course, co-administration of Prevnar, Synagis, and/or rotavirus vaccine is permitted; co-administration of influenza vaccine is permitted at dose 3.

During the booster vaccination, co-administration of Prevnar, hepatitis A vaccine and influenza vaccine is permitted for all subjects in Cohort 1, 2 and 3; and co-administration of measles, mumps, rubella and varicella vaccine is permitted for all subjects in Cohort 2 and 3.

The study will be conducted in a double-blind fashion with regard to consistency of the 3 manufacturing lots of Hib-MenCY-TT vaccine and single-blind fashion for Hib-MenCY-TT vaccine versus monovalent Hib vaccine. The parents/guardians will be blinded up to collection of all data pertaining to the period up to one month after booster vaccination. Therefore, the extended safety follow-up after the booster dose will be conducted in an unblinded manner. The person administering the vaccines will ensure that the parent/guardian does not see the vaccine vial used in reconstituting the vaccine. Due to the differences in the presentations of the candidate Hib-MenCY-TT vaccine and control vaccines, it is not possible to blind study personnel who administer the vaccines.

Eligibility

Ages Eligible for Study:	6 Weeks to 15 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Subjects for whom the investigator believes that parents/guardians 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 or guardian of the subject.
Healthy subjects as established by medical history and clinical examination before entering into the study.
Born after 36 weeks gestation.
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.
Infants may have received a birth dose of Bacillus Calmette-Guérin (BCG) vaccine.

Exclusion Criteria:

Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine(s). (Synagis® [palivizumab, MedImmune], Prevnar (Prevenar), rotavirus vaccine, and influenza vaccine are allowed.
Previous vaccination against Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, and/or poliovirus; more than one previous dose of hepatitis B vaccine.
History of Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, hepatitis B, and/or poliovirus disease.
Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required).
History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including dry natural latex rubber.
Major congenital defects or serious chronic illness.
History of any neurologic disorders or seizures.
Acute disease at time of enrollment.
Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
Concurrent participation in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).

Additional specific criteria for the US subjects in Cohort 1. In addition, for Cohorts 2 and 3, subjects should not be administered M-M-R II and Varivax if any of these criteria apply:

History of measles, mumps, rubella or varicella.
Previous vaccination against measles, mumps, rubella or varicella.
Hypersensitivity to any component of the vaccines, including gelatin or neomycin.
Patients receiving immunosuppressive therapy.
Individuals with blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.
Individuals with primary and acquired immunodeficiency states.
Individuals with a family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.
Individuals with active tuberculosis.
Acute disease at time of booster vaccination.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00289783

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Locations

United States, Alabama
GSK Investigational Site
Birmingham, Alabama, United States, 35235
United States, Arizona
GSK Investigational Site
Phoenix, Arizona, United States, 85003
United States, Arkansas
GSK Investigational Site
Bryant, Arkansas, United States, 72011
GSK Investigational Site
Fayetteville, Arkansas, United States, 72703
GSK Investigational Site
Little Rock, Arkansas, United States, 72205
GSK Investigational Site
Little Rock, Arkansas, United States, 72202
United States, California
GSK Investigational Site
Rolling Hills Estates, California, United States, 90274
GSK Investigational Site
Fresno, California, United States, 93720
GSK Investigational Site
Fountain Valley, California, United States, 92708
GSK Investigational Site
Fresno, California, United States, 93710
GSK Investigational Site
Oakland, California, United States, 94609
GSK Investigational Site
West Covina, California, United States, 91790
GSK Investigational Site
Sacramento, California, United States, 95817
GSK Investigational Site
La Jolla, California, United States, 92037
GSK Investigational Site
East Artesia, California, United States, 90706
GSK Investigational Site
Fresno, California, United States, 93726
United States, Colorado
GSK Investigational Site
Longmont, Colorado, United States, 80501
United States, Florida
GSK Investigational Site
Pembroke Pines, Florida, United States, 33024
GSK Investigational Site
Cocoa Beach, Florida, United States, 32931
United States, Idaho
GSK Investigational Site
Nampa, Idaho, United States, 208 463 3126
United States, Iowa
GSK Investigational Site
West Desmoines, Iowa, United States, 50266
GSK Investigational Site
Des Moines, Iowa, United States, 50309
United States, Kansas
GSK Investigational Site
Kansas City, Kansas, United States, 66160
GSK Investigational Site
Ark City, Kansas, United States, 67005
United States, Kentucky
GSK Investigational Site
Bardstown, Kentucky, United States, 40004
GSK Investigational Site
Lexington, Kentucky, United States, 40503
GSK Investigational Site
Louisville, Kentucky, United States, 40272
United States, Louisiana
GSK Investigational Site
Bossier City, Louisiana, United States, 71111
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21201
United States, Massachusetts
GSK Investigational Site
Jamaica Plain, Massachusetts, United States, 02130
GSK Investigational Site
Fall River, Massachusetts, United States, 02724
United States, Michigan
GSK Investigational Site
Portage, Michigan, United States, 49024
GSK Investigational Site
Stevensville, Michigan, United States, 49127
GSK Investigational Site
Kalamazoo, Michigan, United States, 49008
United States, Minnesota
GSK Investigational Site
St. Paul, Minnesota, United States, 55108
GSK Investigational Site
Brainerd, Minnesota, United States, 56401
United States, Nebraska
GSK Investigational Site
Omaha, Nebraska, United States, 68131
United States, Nevada
GSK Investigational Site
North Las Vegas, Nevada, United States, 89025
United States, New York
GSK Investigational Site
New Hartford, New York, United States, 13413
GSK Investigational Site
Rochester, New York, United States, 14618
GSK Investigational Site
Bronx, New York, United States, 10467
GSK Investigational Site
Stony Brook, New York, United States, 11794
GSK Investigational Site
Ithaca, New York, United States, 14850
GSK Investigational Site
Syracuse, New York, United States, 13210
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27705
GSK Investigational Site
Durham, North Carolina, United States, 27710
GSK Investigational Site
Sylva, North Carolina, United States, 28779
GSK Investigational Site
Raleigh, North Carolina, United States, 27609
United States, Ohio
GSK Investigational Site
Cleveland, Ohio, United States, 44121
GSK Investigational Site
Boardman, Ohio, United States, 44512
GSK Investigational Site
South Euclid, Ohio, United States, 44121
GSK Investigational Site
Huber Heights, Ohio, United States, 45424
GSK Investigational Site
Columbus, Ohio, United States, 43205
GSK Investigational Site
Canton, Ohio, United States, 44718
United States, Oklahoma
GSK Investigational Site
Tulsa, Oklahoma, United States, 74127
United States, Oregon
GSK Investigational Site
Gresham, Oregon, United States, 97030
United States, Pennsylvania
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15241
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19114
GSK Investigational Site
Hershey, Pennsylvania, United States, 17033-0850
GSK Investigational Site
Erie, Pennsylvania, United States, 16501
GSK Investigational Site
Greenville, Pennsylvania, United States, 16125
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15236
GSK Investigational Site
Beaver Falls, Pennsylvania, United States, 15010
United States, South Carolina
GSK Investigational Site
Charleston, South Carolina, United States, 29406
GSK Investigational Site
Lexington, South Carolina, United States, 29072
United States, Texas
GSK Investigational Site
Amarillo, Texas, United States, 79124
GSK Investigational Site
Fort Worth, Texas, United States, 76107
GSK Investigational Site
San Antonio, Texas, United States, 78205
GSK Investigational Site
Temple, Texas, United States, 76508
GSK Investigational Site
Galveston, Texas, United States, 77555-0188
United States, Utah
GSK Investigational Site
South Jordan, Utah, United States, 84095
GSK Investigational Site
St. George, Utah, United States, 84790
GSK Investigational Site
Layton, Utah, United States, 84041
GSK Investigational Site
Pleasant Gorve, Utah, United States, 84062
United States, Virginia
GSK Investigational Site
Norfolk, Virginia, United States, 23510
United States, Washington
GSK Investigational Site
Vancouver, Washington, United States, 98664
United States, Wisconsin
GSK Investigational Site
La Crosse, Wisconsin, United States, 54601
Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Australia, Queensland
GSK Investigational Site
Herston, Queensland, Australia, 4029
GSK Investigational Site
South Brisbane, Queensland, Australia, 4101
Australia, Victoria
GSK Investigational Site
Carlton, Victoria, Australia, 3053
Mexico
GSK Investigational Site
Mexico, D.F., Mexico, 06720

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	103813, 105067
Study First Received:	February 9, 2006
Last Updated:	September 28, 2009
ClinicalTrials.gov Identifier:	NCT00289783 History of Changes
Health Authority:	United States: Food and Drug Administration