Consistency & Immunogenicity Study of 3 Lots of GSK's Hib Conjugate Vaccine Versus ActHIB & Pentacel in Healthy Infants

Haemophilus Influenzae Type b Clinical Trial

Official title:

Phase III, Partially Double-blind Study to Evaluate Consistency and Immunogenicity of 3 Lots of GSK Biologicals' Hib Conjugate Vaccine 208108 Versus ActHIB and Pentacel at 2, 4, 6 and 15-18 Months of Age in Healthy Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01000974
• Other study ID #: 112957
• Status: Completed
• Phase: Phase 3
• Start date: June 18, 2010
• Est. completion date: July 17, 2013

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate safety, to demonstrate lot-to-lot consistency of the vaccine, to address the relevant concomitant vaccine administrations and to provide a comparison between GSK Biologicals' Hib conjugate vaccine and the licensed monovalent Hib vaccine ActHIB as well as the licensed combination product Pentacel in infants at 2, 4, 6 and 15-18 months of age. This study is designed with a primary and a booster phase.

Description:

This protocol posting has been updated following protocol amendment 3, dated 12 April 2011. The impacted section is: Eligibility Criteria (Exclusion criteria).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4003
• Est. completion date: July 17, 2013
• Est. primary completion date: November 18, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 12 Weeks

Eligibility

Inclusion Criteria:

• Subjects for whom the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR[s]) can and will comply with the requirements of the protocol (e.g., completion of the diary card, return for follow-up visits).

• 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 subject's parent/LAR.

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

• Born after a gestation period of minimum 36 weeks.

• 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:

• 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 of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine and until 30 days after the booster dose.

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

• History of Haemophilus influenzae type b, diphtheria, tetanus, pertussis, pneumococcal, rotavirus, poliovirus, and hepatitis B diseases.

• 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.

• Major congenital defects or serious chronic illness.

• History of any neurologic disorders or seizures.

• Acute disease at time of enrollment. All vaccines can be administered to persons with a minor illness.

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

• Concurrent participation in another clinical study, up to 30 days prior to study entry or 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).

• Child in care.

• History of intussusception.

• History of uncorrected congenital malformation of the gastrointestinal tract that would predispose the infant to intussusception.

• History of Severe Combined Immunodeficiency Disease.

Related Conditions & MeSH terms

• Haemophilus Influenzae Type b

Intervention

Biological:
• GSK Biologicals' Haemophilus influenzae type b vaccine (GSK 208108)
Three doses of 3 different manufacturing lots in primary study at 2, 4 and 6 months of age as intramuscular injection and one dose as booster vaccination.
• ActHIB™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection and one dose as a booster vaccination
• Pentacel™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection and one dose as a booster vaccination
• Pediarix™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
• Prevnar 13™
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
• Rotarix™
Two oral doses in primary epoch at 2 and 4 months of age
• Engerix™-B
Two or three doses in primary epoch at 2,( 4) and 6 months of age as intramuscular injection
• Infanrix™
One dose in the booster epoch at 15-18 months of age as intramuscular injection

Locations

Country	Name	City	State
United States	GSK Investigational Site	Amarillo	Texas
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Antioch	California
United States	GSK Investigational Site	Bardstown	Kentucky
United States	GSK Investigational Site	Benton	Arkansas
United States	GSK Investigational Site	Boulder	Colorado
United States	GSK Investigational Site	Bountiful	Utah
United States	GSK Investigational Site	Canton	Ohio
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Daly City	California
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	Dothan	Alabama
United States	GSK Investigational Site	Erie	Pennsylvania
United States	GSK Investigational Site	Fall River	Massachusetts
United States	GSK Investigational Site	Fargo	North Dakota
United States	GSK Investigational Site	Fayetteville	Arkansas
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Fountain Valley	California
United States	GSK Investigational Site	Fremont	California
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Greenville	Pennsylvania
United States	GSK Investigational Site	Hayward	California
United States	GSK Investigational Site	Hermitage	Pennsylvania
United States	GSK Investigational Site	Honolulu	Hawaii
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Layton	Utah
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Madison	Wisconsin
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Marshfield	Wisconsin
United States	GSK Investigational Site	Mineola	New York
United States	GSK Investigational Site	Nampa	Idaho
United States	GSK Investigational Site	Oakland	California
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Orange City	Florida
United States	GSK Investigational Site	Redwood City	California
United States	GSK Investigational Site	Roseville	California
United States	GSK Investigational Site	Roy	Utah
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Saint Paul	Minnesota
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	Santa Clara	California
United States	GSK Investigational Site	Santa Rosa	California
United States	GSK Investigational Site	South Jordan	Utah
United States	GSK Investigational Site	Stevensville	Michigan
United States	GSK Investigational Site	Sugar Land	Texas
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Syracuse	Utah
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Utica	New York
United States	GSK Investigational Site	Vallejo	California
United States	GSK Investigational Site	Waipio	Hawaii
United States	GSK Investigational Site	Walnut Creek	California
United States	GSK Investigational Site	West Covina	California
United States	GSK Investigational Site	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (=) 0.15 Microgram Per Milliliter (µg/mL) and = 1.0 µg/mL	Non-inferiority of Hiberix to ActHIB, each co-administered with Pediarix, Prevnar13 and Rotarix following 3 primary doses in terms of immune response to PRP (Anti-PRP= 0.15 µ g/ml and =1.0 µg/mL).	At 1 month after last dose of primary vaccination
Primary	Number of Subjects With Anti-Protein-D (Anti-D) and Anti-Protein-T (Anti-T) Antibody Concentrations = 0.1 International Units Per Milliliter (IU/mL)	Non-inferiority of Pediarix co-administered with Hiberix, Prevnar13 and Rotarix compared to Pediarix co-administered with ActHIB, Prevnar13 and Rotarix following 3 primary vaccine doses in terms of immune response to Diphtheria, Tetanus.	At 1 month after last dose of primary vaccination
Primary	Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations	Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).	At 1 month after last dose of primary vaccination
Primary	Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibody Concentrations	Antibody concentrations were given as geometric mean concentrations (GMCs) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter i.e. EL.U/mL.	At 1 month after last dose of primary vaccination
Primary	Anti-Streptococcus Pneumoniae (S.Pneumoniae) Antibody Concentrations	Antibody concentrations against S.pneumoniae were given as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).	At 1 month after last dose of primary vaccination
Primary	Number of Subjects With Seroresponse (95%) to Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA)	Seroresponse (95%) was defined as the number of subjects showing a concentration above a threshold that leads to 95% seroresponse in the ActHIB group.	At 1 month after last dose of primary vaccination
Primary	Number of Subjects With Anti-Polio 1,2,3 Antibody Titres Greater Than or Equal to Cut-off Value	The cut-off value was defined as a concentration = 8 ED50 (ED50 is the concentration at which the protein exhibits 50% of its maximum activity).; The polio testing which started at the Biomnis laboratory was stopped because the polio virus micro-neutralization assays were found to be not in line with the quality standards defined in GSK Biologicals' SOPs. As a result, polio testing was restarted at the GSK laboratory and the results were uploaded into the clinical database.	At 1 month after last dose of primary vaccination
Primary	Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations = 1.0 µg/mL	Non-inferiority of a booster dose of Hiberix co-administered with Infanrix in subjects 15-18 months of age who received 3 primary vaccine doses of Hiberix to a booster dose of ActHIB co-administered with Infanrix in subjects of 15-18 months of age who received 3 primary vaccine doses of ActHIB in terms of immune response to PRP	At 1 month after booster vaccination
Secondary	Anti-protein-D (Anti-D) and Anti-protein-T (Anti-T) Antibody Concentrations	Antibody concentrations were given as geometric mean concentrations (GMCs) and expressed as International Units per milliliter (IU/mL).	At 1 month after last dose of primary vaccination
Secondary	Number of Subjects With Any Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any symptom regardless of intensity grade.	During a 4-day follow-up period (Days 0-3) following any vaccination
Secondary	Number of Subjects With Any Solicited General Symptoms	Assessed solicited general symptoms were drowsiness, irritability, fever and loss of appetite. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Any fever= Rectal temperature equal to or above (=) 38 degrees Celsius (°C).	During a 4-day follow-up period (Days 0-3) following any vaccination
Secondary	Number of Subjects With Any Unsolicited Adverse Events (AEs).	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.	During the 31-day (Day 0-Day 30) follow-up period after primary vaccination
Secondary	Number of Subjects With 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.	From Day 0 until 6 months following the last primary dose
Secondary	Number of Subjects With AEs of Specific Interest (AESIs)	An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.	From Day 0 until 6 months following the last primary dose or the receipt of the booster vaccination, whichever comes first
Secondary	Number of Subjects With Seroresponse (90%) to Anti-PT, Anti-PRN and Anti-FHA	Seroresponse (90%) was defined as the number of subjects showing a concentration above a threshold that leads to 90% seroresponse in the ActHIB group.	At 1 month after last dose of primary vaccination
Secondary	Number of Subjects With Anti-PT, Anti-PRN and Anti-FHA Antibody Concentrations = 5 EL.U/mL	Seroresponse was defined as the number of subjects showing a concentration above a threshold that leads to 90% seroresponse in the ActHIB group.	At 1 month after last dose of primary vaccination
Secondary	Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations = 0.15 µg/mL and = 1.0 µg/mL	Evaluation of persistence of anti-PRP antibodies induced by three primary vaccine doses of Hiberix, and ActHIB, each co-administered with Pediarix, Prevnar 13 and Rotarix, or Pentacel co-administered with Engerix-B, Rotarix and Prevnar 13 prior to the booster dose of Hiberix, ActHIB or Pentacel at 15-18 months of age and evaluation of immunogenicity of a booster dose of Hiberix co-administered with Infanrix, ActHIB co-administered with Infanrix and Pentacel in terms of the percentage of subjects with anti-PRP concentrations =0.15 µg/mL, =1.0 µg/mL and GMCs one month after the booster dose.	Prior to the booster vaccination and 1 month after the booster vaccination
Secondary	Anti-Hepatitis B (Anti-HBs) Antibody Concentrations	Antibody concentrations were tabulated as geometric mean concentrations (GMCs) and expressedas milli-international units per milliliter (mIU/mL).	At 1 month after last dose of primary vaccination
Secondary	Number of Subjects With S.Pneumoniae Antibody Concentrations = 0.05 µg/mL, = 0.2 µg/mL and =1.0 µg/mL	Evaluation of immunogenicity of a 3-dose primary vaccination course of Prevnar 13 co-administered with Hiberix, Rotarix and Pediarix, of Prevnar 13 co-administered with ActHIB, Rotarix and Pediarix and of Prevnar 13 co-administered with Pentacel, Rotarix and Engerix-B in terms of S.pneumoniae GMCs and antibody concentrations = 0.05µg/mL, = 0.2 µg/mL, = 1.0 µg/mL at one month after the last dose of primary vaccination.	At 1 month after the last dose of primary vaccination
Secondary	Antibody Titers for Poliovirus Types 1, 2 and 3	Antibody titers were given as geometric mean titers(GMTs).	At 1 month after last dose of primary vaccination
Secondary	Number of Subjects With Anti-HBs Antibody Concentrations Greater Than or Equal to Cut-off Values	The cut-off values were defined as a concentration= 3.3 mIU/mL (seropositivity) and = 10 mIU/mL (seroprotection).	At 1 month after last dose of primary vaccination
Secondary	Anti-polyribosylribitol Phosphate (PRP) Antibody Concentrations	Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).	Prior to the booster vaccination and 1 month after the booster vaccination
Secondary	Anti-Hepatitis B (Anti-HBs) Antibody Concentrations =10.0 mIU/mL and =6.2 mIU/mL	Antibody concentrations were expressed as geometric mean concentrations (GMCs) and expressed as milli-international units per milliliter (mIU/mL).	Prior to the booster vaccination
Secondary	Number of Subjects With Anti-HB Antibody Concentrations =10.0 mlU/mL and =6.2mLU/mL	The cut-off values were defined as a concentration= 6.2 mIU/mL (seropositivity) and = 10 mIU/mL (seroprotection).	Prior to booster vaccination
Secondary	Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations = 5 EL.U/mL	Evaluation of persistence of anti-PT, anti-FHA and anti-PRN antibodies induced by Pediarix or Pentacel and Engerix-B prior to the administration of a booster dose of Hib vaccine at 15-18 months of age and evaluation of immunogenicity of a booster dose of Infanrix co-administered with Hiberix, a booster dose of Infanrix co-administered with ActHIB and a booster dose of Pentacel with respect to anti-PT, anti-FHA and anti- PRN antibodies.	Prior to the booster vaccination and 1 month after the booster vaccination
Secondary	Anti-poliovirus Types 1, 2, and 3 Antibody Titres and Titres = 8	Antibody concentrations were tabulated as geometric mean titers (GMTs) and expressed as titers.	Prior to the booster vaccination
Secondary	Number of Subjects With Anti-Polio-1,2,3 Antibody Titers = 8	Anti-polio 1,2,3 antibody titers greater or equal to the cut off value were calculated.	Prior to booster vaccination
Secondary	Number of Subjects With Anti-D and Anti-T Antibody Concentrations = 0.1 IU/mL and =1.0 IU/mL, Respectively.	Evaluation of persistence of anti-D, anti-T antibodies induced by Pediarix or Pentacel and Engerix-B prior to the administration of a booster dose of Hib vaccine at 15-18 months of age and evaluation of immunogenicity of a booster dose of Infanrix co-administered with Hiberix, a booster dose of Infanrix co-administered with ActHIB and a booster dose of Pentacel with respect to anti-D and anti-T antibodies.	Prior to the booster vaccination and 1 month after the booster vaccination
Secondary	Number of Subjects With Any Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any symptom regardless of intensity grade.	Within 4 days (Days 0-3) following the booster dose
Secondary	Number of Subjects With Any Solicited General Symptoms	Assessed solicited general symptoms were drowsiness, irritability, fever and loss of appetite. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Any fever= Axillary temperature equal to or above (=) 38 degrees Celsius (°C).	Within 4 days (Days 0-3) following the booster dose
Secondary	Number of Subjects With AEs of Specific Interest (AESIs)	An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.	From booster dose until 6 months following receipt of the booster dose
Secondary	Number of Subjects With Any Unsolicited Adverse Events (AEs).	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.	Within 31 days (Day 0 to Day 30) following the booster dose
Secondary	Number of Subjects With Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	From the booster dose until 6 months following receipt of the booster dose
Secondary	Anti-FHA, Anti-PRN and Anti-PT Antibody Concentrations	Antibody concentrations were given as geometric mean concentrations (GMCs) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter i.e. EL.U/mL.	pre-booster and one month after booster vaccination

External Links

•   IPD for this study will be made available via the Clinical Study Data Request site.