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

NCT01000974 | Completed Phase 3 Results

• 1 other identifier: 112957
• Study Type: interventional
• Target: 4,003
• Locations: 1 country
• Sites: 63

Brief 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.

Conditions

Haemophilus Influenzae Type b

Keywords

primary vaccination course; Haemophilus influenzae type b; infants, children; booster vaccination; immunogenicity; safety; Gram-negative bacterial infections; vaccines, conjugate

Outcome Measures

Primary Outcomes (8)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (26)

• Anti-protein-D (Anti-D) and Anti-protein-T (Anti-T) Antibody Concentrations

  At 1 month after last dose of primary vaccination

• Number of Subjects With Any Solicited Local Symptoms

  During a 4-day follow-up period (Days 0-3) following any vaccination

• Number of Subjects With Any Solicited General Symptoms

  During a 4-day follow-up period (Days 0-3) following any vaccination

• Number of Subjects With Any Unsolicited Adverse Events (AEs).

  During the 31-day (Day 0-Day 30) follow-up period after primary vaccination

• Number of Subjects With Serious Adverse Events (SAEs)

  From Day 0 until 6 months following the last primary dose

Study Arms (3)

Hiberix Group

EXPERIMENTAL

Pooled group of subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of 3 different lots of Hiberix® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age The Hiberix® vaccine was administered intramuscularly in the right thigh. Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.

Biological: GSK Biologicals' Haemophilus influenzae type b vaccine (GSK 208108); Biological: Pediarix™; Biological: Prevnar 13™; Biological: Rotarix™; Biological: Infanrix™

ActHIB Group

ACTIVE COMPARATOR

Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of ActHIB® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The ActHIB® vaccine was administered intramuscularly in the right thigh. The Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.

Biological: ActHIB™; Biological: Pediarix™; Biological: Prevnar 13™; Biological: Rotarix™; Biological: Infanrix™

Pentacel Group

ACTIVE COMPARATOR

Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of Pentacel® vaccine co-administered with 3 doses of Prevnar13® vaccine, 2 or 3 doses of Engerix™-B vaccine at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The Pentacel® vaccine was administered intramuscularly in the right thigh. The Engerix™-B vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally. If subjects in the Pentacel Group had received a birth dose of Hepatitis B vaccine then they were to receive Engerix™-B vaccine only at 2 and 6 months of age.

Biological: Pentacel™; Biological: Prevnar 13™; Biological: Rotarix™; Biological: Engerix™-B

Interventions

GSK Biologicals' Haemophilus influenzae type b vaccine (GSK 208108) BIOLOGICAL

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.

Also known as: Hiberix®

Hiberix Group

ActHIB™ BIOLOGICAL

Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection and one dose as a booster vaccination

ActHIB Group

Pentacel™ BIOLOGICAL

Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection and one dose as a booster vaccination

Pentacel Group

Pediarix™ BIOLOGICAL

Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection

ActHIB Group; Hiberix Group

Prevnar 13™ BIOLOGICAL

Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection

ActHIB Group; Hiberix Group; Pentacel Group

Rotarix™ BIOLOGICAL

Two oral doses in primary epoch at 2 and 4 months of age

ActHIB Group; Hiberix Group; Pentacel Group

Engerix™-B BIOLOGICAL

Two or three doses in primary epoch at 2,( 4) and 6 months of age as intramuscular injection

Pentacel Group

Infanrix™ BIOLOGICAL

One dose in the booster epoch at 15-18 months of age as intramuscular injection

ActHIB Group; Hiberix Group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (63)

GSK Investigational Site

Dothan, Alabama, 36305, United States

Location

GSK Investigational Site

Benton, Arkansas, 72019, United States

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GSK Investigational Site

Fayetteville, Arkansas, 72703, United States

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GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

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GSK Investigational Site

Little Rock, Arkansas, 72205, United States

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GSK Investigational Site

Anaheim, California, 92804, United States

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GSK Investigational Site

Antioch, California, 94509, United States

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GSK Investigational Site

Daly City, California, 94015, United States

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GSK Investigational Site

Fountain Valley, California, 92708, United States

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GSK Investigational Site

Fremont, California, 94538, United States

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GSK Investigational Site

Fresno, California, 93726, United States

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GSK Investigational Site

Hayward, California, 94545, United States

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GSK Investigational Site

Huntington Beach, California, 92647, United States

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GSK Investigational Site

Oakland, California, 94612, United States

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GSK Investigational Site

Redwood City, California, 94063, United States

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GSK Investigational Site

Roseville, California, 95661, United States

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GSK Investigational Site

Sacramento, California, 95815, United States

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GSK Investigational Site

Sacramento, California, 95823, United States

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GSK Investigational Site

San Jose, California, 95119, United States

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GSK Investigational Site

Santa Clara, California, 95051, United States

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GSK Investigational Site

Santa Rosa, California, 95403, United States

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GSK Investigational Site

Vallejo, California, 94589, United States

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GSK Investigational Site

Walnut Creek, California, 94596, United States

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GSK Investigational Site

West Covina, California, 91790, United States

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GSK Investigational Site

Boulder, Colorado, 80304, United States

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GSK Investigational Site

Colorado Springs, Colorado, 80922, United States

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GSK Investigational Site

Orange City, Florida, 32763, United States

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GSK Investigational Site

Marietta, Georgia, 30062, United States

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GSK Investigational Site

Woodstock, Georgia, 30189, United States

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GSK Investigational Site

Honolulu, Hawaii, 96819, United States

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GSK Investigational Site

Waipio, Hawaii, 96797, United States

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GSK Investigational Site

Nampa, Idaho, 83686, United States

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GSK Investigational Site

Bardstown, Kentucky, 40004, United States

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GSK Investigational Site

Louisville, Kentucky, 40291, United States

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GSK Investigational Site

Fall River, Massachusetts, 02721, United States

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GSK Investigational Site

Stevensville, Michigan, 49127, United States

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GSK Investigational Site

Saint Paul, Minnesota, 55108, United States

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GSK Investigational Site

Omaha, Nebraska, 68131, United States

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GSK Investigational Site

Mineola, New York, 11501, United States

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GSK Investigational Site

Syracuse, New York, 13210, United States

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GSK Investigational Site

Utica, New York, 13502, United States

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GSK Investigational Site

Fargo, North Dakota, 58103, United States

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GSK Investigational Site

Canton, Ohio, 44718, United States

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GSK Investigational Site

Cincinnati, Ohio, 45229, United States

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GSK Investigational Site

Cleveland, Ohio, 44121, United States

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GSK Investigational Site

Dayton, Ohio, 45406, United States

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GSK Investigational Site

Tulsa, Oklahoma, 74107, United States

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GSK Investigational Site

Erie, Pennsylvania, 16505, United States

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GSK Investigational Site

Greenville, Pennsylvania, 16125, United States

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GSK Investigational Site

Hermitage, Pennsylvania, 16148, United States

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GSK Investigational Site

Charleston, South Carolina, 29406, United States

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GSK Investigational Site

Amarillo, Texas, 79124, United States

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GSK Investigational Site

Fort Worth, Texas, 76107, United States

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GSK Investigational Site

Houston, Texas, 77055, United States

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GSK Investigational Site

Sugar Land, Texas, 77479, United States

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GSK Investigational Site

Bountiful, Utah, 84010, United States

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GSK Investigational Site

Layton, Utah, 84041, United States

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GSK Investigational Site

Roy, Utah, 84067, United States

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GSK Investigational Site

Salt Lake City, Utah, 84109, United States

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GSK Investigational Site

South Jordan, Utah, 84095, United States

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GSK Investigational Site

Syracuse, Utah, 84075, United States

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GSK Investigational Site

Madison, Wisconsin, 53792, United States

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GSK Investigational Site

Marshfield, Wisconsin, 54449, United States

Location

Related Links

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

MeSH Terms

Conditions

Haemophilus Infections; Gram-Negative Bacterial Infections

Interventions

Hiberix; Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; pentacel; PEDIARIX; 13-valent pneumococcal vaccine; RIX4414 vaccine; Diphtheria-Tetanus-acellular Pertussis Vaccines

Condition Hierarchy (Ancestors)

Pasteurellaceae Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Pertussis Vaccine; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined; Vaccines, Acellular; Vaccines, Subunit

Limitations and Caveats

Anti-HBs antibody concentration cut off defining seropositivity was based on 6.2 mIU/mL instead of 3.3 mIU/mL for the pre-booster vaccination phase as tested by the commercial assay Centaur

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: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2009
• First Posted: October 23, 2009
• Study Start: June 18, 2010
• Primary Completion: November 18, 2011
• Study Completion: July 17, 2013
• Last Updated: July 12, 2018
• Results First Posted: August 19, 2013

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (63)