Comparison of DTaP-IPV-Hep B-PRP~T Combined Vaccine to CombAct-HIB® Concomitantly Given With Engerix B® Paediatric and OPV

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00362336
First received: August 8, 2006
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to document the immunological response to the investigational hexavalent vaccine at the 6, 10, and 14 weeks schedule

The primary objective is to demonstrate that the hexavalent DTaP-IPV-HB-PRP~T combined vaccine does not induce lower immune responses than CombAct-HIB® with Engerix B® Paediatric and OPV in terms of seroprotection rates to Diphtheria (D), Tetanus (T), polio, Hepatitis B (HB), and Polyribosyl ribitol phosphate (PRP), one month after a 3-dose primary series (6, 10, and 14 weeks) with no HB vaccination at birth.

The secondary Objectives are:

To describe the safety in terms of any adverse events in the first 28 days after each injection and any serious adverse events during the entire trial.

To describe Immunogenicity after the primary series and prior to and after a booster vaccination.


Condition Intervention Phase
Hepatitis B
Polio
Diphtheria
Pertussis
Haemophilus Influenzae Type b
Biological: DTaP-IPV-HB-PRP~T
Biological: CombAct-HIB®
Biological: Engerix B® Pediatric
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunogenicity Study of a DTaP-IPV-Hep B-PRP~T Combined Vaccine in Comparison to CombAct-HIB® Concomitantly Administered With Engerix B® Paediatric and OPV at 6, 10, and 14 Weeks of Age in South African Infants

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of Participants With Seroprotection After Primary Series Vaccination With DTaP-IPV-Hep B-PRT~T or CombAct Hib™ + Engerix B™ + Oral Polio Vaccine (OPV) [ Time Frame: 1 month post-Dose 3 ] [ Designated as safety issue: No ]
    Antibodies were measured by the following methods: anti-Hepatitis B (Hep B) by enhanced chemiluminescence detection, anti-Haemophilus influenzae type b (Hib) by Farr type radio immunoassay, anti-Diphtheria (D) by toxin neutralization assay, anti-Tetanus (T) by indirect enzyme-linked immunosorbent assay (ELISA), and anti-Poliovirus types 1, 2, and 3 by neutralization assay. Seroprotection was defined as the following antibody titers: Anti-Tetanus ≥ 0.01 International Unit (IU)/mL; Anti-Diphtheria ≥ 0.01 IU/mL; Anti-Hepatitis B ≥ 10 mIU/mL; Anti-Polyribosyl ribitol phosphate ≥ 0.15 µg/mL; Anti-polio 1, 2, and 3 ≥ 8 (1/dil).


Secondary Outcome Measures:
  • Number of Participants Attaining Other Seroprotection and Seroconversion Titers After Primary Series Vaccination With DTaP-IPV-Hep B-PRT~T (With or Without Engerix B™ at Birth) or CombAct Hib™ + Engerix B™ + Oral Polio Vaccine (OPV) [ Time Frame: 1 month post-Dose 3 ] [ Designated as safety issue: No ]
    Anti-Hepatitis B (Hep B) was measured by enhanced chemiluminescence detection, anti-Haemophilus influenzae type b (Hib) by Farr type radio immunoassay, anti diphtheria by toxin neutralization assay, anti-Tetanus (T) by indirect enzyme-linked immunosorbent assay (ELISA), and anti-Pertussis toxoid (PT) and anti-Filamentous hemagglutinin (FHA) by ELISA. Seroprotection was defined as a titer ≥ 100 mIU/mL for anti-Hep B; ≥ 1 µg/mL for anti-PRP; ≥ 0.1 IU/mL (Level 1) and ≥ 1.0 IU/mL (Level 2) for anti-Diphtheria and anti-Tetanus. Seroconversion for anti-PT and anti-FHA was a ≥ 4-fold increase from baseline.

  • Geometric Mean Titers (GMTs) of Antibodies After Primary Series Vaccination With DTaP-IPV-Hep B-PRT~T (With or Without Engerix B™ at Birth) or CombAct Hib™ + Engerix B™ + Oral Polio Vaccine (OPV) [ Time Frame: Day 42 before Dose 1 and 1 month post-Dose 3 ] [ Designated as safety issue: No ]
    Anti-Hepatitis B (Hep B) was measured by enhanced chemiluminescence detection, anti-Haemophilus influenzae type b (Hib) by Farr type radio-immunoassay, anti-Diphtheria by toxin neutralization assay, anti-Tetanus by indirect enzyme-linked immunosorbent assay (ELISA), anti-Poliovirus types 1, 2, and 3 by neutralization assay, and anti-Pertussis toxoid (PT) and anti-Filamentous hemagglutinin (FHA) by ELISA.

  • Number of Participants With Antibody Persistence Pre-Booster and Response Post-Booster Vaccination With DTaP-IPV-Hep B-PRT~T (With or Without Engerix B™ at Birth) or CombAct Hib™ + Engerix B™ + OPV [ Time Frame: Day 540 pre-booster and Day 570 post-booster ] [ Designated as safety issue: No ]
    Antibodies were measured by the following methods: anti-Hepatitis B (Hep B) by enhanced chemiluminescence detection, anti-Haemophilus influenzae type b (PRP) by Farr type radio immunoassay, anti-Diphtheria by toxin neutralization assay, anti-Tetanus by indirect enzyme-linked immunosorbent assay (ELISA), anti-poliovirus types 1, 2, and 3 by neutralization assay. Persistence and response were defined as a titer ≥ 10 mIU/mL for anti-Hep B, ≥ 0.15 µg/mL for anti-PRP, ≥ 0.01 IU/mL for anti-Diphtheria and anti-Tetanus, ≥ 8 (1/dil) for anti-Poliovirus, and ≥ 4 EU/mL for anti-PT and anti-FHA.

  • Geometric Mean Titers (GMTs) of Antibodies Pre- and Post-Booster Vaccination With DTaP-IPV-Hep B-PRT~T (With or Without Engerix B™ at Birth) or CombAct Hib™ + Engerix B™ + OPV [ Time Frame: Day 540 pre-booster and Day 570, post-booster ] [ Designated as safety issue: No ]
    Anti-Hepatitis B (Hep B) was measured by enhanced chemiluminescence detection, anti-Haemophilus influenzae type b (PRP) by Farr type radio immunoassay, anti-Diphtheria by toxin neutralization assay, anti-Tetanus (T) by indirect enzyme-linked immunosorbent assay (ELISA), anti-Poliovirus types 1, 2, and 3 by neutralization assay, and anti-Pertussis toxoid (PT) and anti-Filamentous hemagglutinin (FHA) by ELISA.

  • Number of Participants With Solicited Injection Site and Systemic Reactions After Primary Vaccination Series With With DTaP-IPV-Hep B-PRT~T (With or Without Engerix B™ at Birth) or CombAct Hib™ + Engerix B™ + Oral Polio Vaccine (OPV). [ Time Frame: Day 0 up to Day 7 post each dose ] [ Designated as safety issue: No ]
    Solicited Injection Site Reactions: Pain, Erythema, Swelling. Solicited System Reactions: Fever (Temperature), Vomiting, Crying, Somnolence, Anorexia, Irritability. Grade 3 was defined as: Pain - crying when injected limb is moved or the movement reduced; Erythema and Swelling - ≥ 5 cm; Fever - temperature ≥ 39.0ºC; Vomiting - ≥ 6 episodes/24 hours or requiring parenteral hydration; Crying abnormal - > 3 hours; Somnolence - sleeping most of the time or difficulty to wake up; Anorexia - refusing ≥ 3 feeds or refusing most feeds/meals; and Irritability - inconsolable.

  • Number of Participants With Solicited Injection Site (Study Vaccine Site) and Systemic Reactions After Booster Vaccination With DTaP-IPV-Hep B-PRT~T (With or Without Engerix B™ at Birth) or CombAct Hib™ + Engerix B™ + Oral Polio Vaccine (OPV) [ Time Frame: Day 0 up to 7 post-booster vaccination ] [ Designated as safety issue: No ]
    Solicited Injection Site Reactions: Pain, Erythema, Swelling, and Extensive swelling of vaccinated limb. Solicited System Reactions: Fever (Temperature), Vomiting, Crying, Somnolence, Anorexia, and Irritability. Grade 3 was defined as: Pain, crying when injected limb is moved or the movement reduced; Erythema and Swelling, ≥ 5 cm; Fever, temperature ≥ 39.0ºC; Vomiting, ≥ 6 episodes/24 hours or requiring parenteral hydration; Crying, > 3 hours; Somnolence, sleeping most of the time or difficulty to wake up; Anorexia, refusing ≥ 3 feeds or refusing most feeds/meals; and Irritability, inconsolable.


Enrollment: 622
Study Start Date: August 2006
Study Completion Date: August 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: DTaP-IPV-Hep B-PRP-T Biological: DTaP-IPV-HB-PRP~T
0.5 mL, Intramuscular (IM)
Experimental: Group 2: CombAct-HIB™ + OPV Biological: CombAct-HIB®
0.5 mL, IM
Active Comparator: Group 3: DTaP-IPV-Hep B-PRP-T (ENGERIX B™ at birth) Biological: Engerix B® Pediatric
0.5 mL, IM

  Eligibility

Ages Eligible for Study:   up to 3 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 0 to 3 day old infants
  • Mother seronegative for Human Immunodeficiency Virus (HIV)
  • Born at full term of pregnancy (≥ 37 weeks) with a birth weight ≥ 2.5 kg
  • Apgar score >7 at 5 or 10 minutes of life
  • Informed consent form signed by a parent or other legal guardian and by an independent witness if the parent or other legal guardian is illiterate
  • Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

  • Current or planned participation in another clinical trial during the entire duration of the present trial
  • Suspected congenital or acquired immunodeficiency
  • Suspected maternal acute seroconversion syndrome to HIV after 24 weeks gestation based on clinical history
  • Chronic illness at a stage that could interfere with trial conduct or completion
  • Blood or blood-derived products received since birth
  • Any planned vaccination (except Bacille Calmette Guérin and trial vaccinations) from birth to 18 weeks of age
  • Oral Poliovirus Vaccine (OPV) administration at birth
  • Known maternal history of HIV, Hepatitis B (HB) (HbsAg carrier) or Hepatitis C seropositivity
  • Thrombocytopenia or bleeding disorder contraindicating intramuscular (IM) vaccination
  • History of seizures
  • Febrile or acute illness on the day of inclusion.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00362336

Locations
South Africa
Soweto, Johannesburg, South Africa, 2013
Bertsham, South Africa
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Clinical Trials Sanofi Pasteur Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00362336     History of Changes
Other Study ID Numbers: A3L15
Study First Received: August 8, 2006
Results First Received: February 14, 2014
Last Updated: April 1, 2014
Health Authority: South Africa: Department of Health

Keywords provided by Sanofi:
Hepatitis B
Polio
Diphtheria
Pertussis
H. influenzae type b

Additional relevant MeSH terms:
Diphtheria
Hepatitis
Hepatitis A
Hepatitis B
Influenza, Human
Whooping Cough
Poliomyelitis
Corynebacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Orthomyxoviridae Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Bordetella Infections
Gram-Negative Bacterial Infections
Infection
Myelitis
Central Nervous System Viral Diseases
Central Nervous System Infections
Central Nervous System Diseases

ClinicalTrials.gov processed this record on September 14, 2014