DTaP-IPV-Hep B-PRP~T Combined Vaccine Versus DTaP-IPV//PRP~T Combined Vaccine + Hep B Vaccine in Hep B Primed Infants

Immunogenicity and Safety of Sanofi Pasteur's DTaP-IPV-Hep B-PRP~T Combined Vaccine at 2, 4, and 6 Months of Age Versus Sanofi Pasteur's DTaP IPV//PRP~T Combined Vaccine at 2, 4, and 6 Months of Age + Hep B Vaccine at 1 and 6 Months of Age, in South Korean Infants Primed With Hep B at Birth

The aim of this study is to evaluate the immunogenicity and safety of a novel DTaP-IPV-Hep B-PRP~T fully liquid combined hexavalent vaccine (study vaccine) administered at 2, 4, and 6 months of age compared to Sanofi Pasteur's DTaP-IPV//PRP~T combined vaccine (Pentaxim™) given at 2, 4, and 6 months of age and Hep B vaccine (Euvax B®) given at 1 and 6 months of age in South Korean infants that received a birth dose of Hep B and born to mothers documented to be serum anti-HBs Ag negative.

Primary Objective

• To demonstrate the non-inferiority in terms of seroprotection (Diphtheria, Tetanus, poliovirus types 1, 2, and 3, PRP-T, Hep B) and vaccine response for pertussis antigens (pertussis toxoid [PT] and filamentous haemagglutinin [FHA]) of Group A versus Group B, one month after the third dose of combined vaccines.

Secondary Objectives:

• To further study the immunogenicity of the two vaccination schemes, before the first dose and one month after the last dose of vaccines.
• To study the safety after each and any dose of vaccines administered in the two vaccination schemes

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Pertussis; Tetanus; Diphtheria; Poliomyelitis; Haemophilus Influenzae Type b Infection
• Intervention / Treatment: Biological: DTaP-IPV-Hep B-PRP~T combined vaccine; Biological: DTaP-IPV//PRP~T and Hepatitis B vaccine

Detailed Description

Study participants who received a first dose of recombinant Hep B vaccine at birth will receive either DTaP-IPV-Hep B-PRP~T combined vaccine at 2, 4, and 6 months of age + 3 doses of Hep B vaccine or Hep B vaccine (Euvax B®) at 1 and 6 months of age and DTaP IPV//PRP~T combined vaccine (Pentaxim™) at 2, 4, and 6 months of age, according to the official vaccination schedule for Hep B, DTaP, poliovirus, and Hib vaccinations in South Korea.

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daejeon, Korea, Republic of, 301 724
  • Gyeonggi Do, Korea, Republic of
  • Gyeonggi do, Korea, Republic of, 425 707
  • Gyeongsangnam do, Korea, Republic of, 641 560
  • Gyeongsangnam do, Korea, Republic of
  • Jeollabuk do, Korea, Republic of, 570 711
  • Jeonbuk, Korea, Republic of, 561 712
  • Kangwon do, Korea, Republic of, 220 701
  • Kyunggi Do, Korea, Republic of, 420 717
  • Seoul, Korea, Republic of
  • Seoul, Korea, Republic of, 120 752
  • Seoul, Korea, Republic of, 130 87
  • Seoul, Korea, Republic of, 137 701
  • Seoul, Korea, Republic of, 139 709
  • Seoul, Korea, Republic of, 158 710
  • Suwon Gyeonggi do, Korea, Republic of, 442 723

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 30 to 40 days on the day of the first study visit
• Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg
• Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative
• Participant and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures
• Born to known hepatitis B surface antigen (HBsAg) seronegative mother (documented laboratory result of HBsAg assay from the maternal blood sample is available)
• Have received one documented dose of Hep B vaccine at birth according to the national recommendations.

Exclusion Criteria:

• Participation in the 4 weeks preceding the trial inclusion or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding any trial vaccination (except Bacille Calmette Guerin (BCG) vaccine) or planned receipt of any vaccine in the 8 days following any trial vaccination
• Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B (except the dose of Hep B vaccine given at birth) diseases or Haemophilus influenzae type b infection with either the trial vaccine or another vaccine
• Past or current receipt of immune globulins, blood or blood-derived products or planned administration during the trial
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, since birth; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks since birth)
• Known personal or maternal history of Human Immunodeficiency Virus (HIV) or hepatitis C seropositivity
• History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Haemophilus influenzae type b infection, confirmed either clinically, serologically, or microbiologically
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
• Known thrombocytopenia, as reported by the parent/legally acceptable representative
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
• In an emergency setting, or hospitalized involuntarily
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study
• History of seizures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Participants will receive 3 injections of the study vaccine (DTaP-IPV-Hep B-PRP~T combined vaccine) at 2, 4, and 6 months of age	Biological: DTaP-IPV-Hep B-PRP~T combined vaccine; 0.5 mL, Intramuscular
Active Comparator: Group B; Participants will receive 2 injections of monovalent Hep B vaccine (Euvax B®) at age 1 and 6 months and 3 injections of DTaP IPV//PRP~T vaccine (Pentaxim™) at age 2, 4, and 6 months	Biological: DTaP-IPV//PRP~T and Hepatitis B vaccine; 0.5 mL, Intramuscular; Other Names: Euvax B®; Pentaxim™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with anti-Diphtheria antibody concentrations ≥ 0.01 International Units (IU)/mL	Anti-Diphtheria antibodies will be measured by a toxin neutralization test	1 month post third vaccination
Number of participants with anti-Tetanus antibody concentrations ≥ 0.1 International unit (IU)/mL	Anti-Tetanus antibodies will be measured by enzyme-linked immunosorbent assay (ELISA).	1 month post third vaccination
Number of participants with ≥ 4 fold increase in anti-PT and anti-FHA antibody concentrations (EU/mL) from 1 month pre-dose 1 to 1 month post-dose 3	Anti-PT and anti-FHA antibodies will be measured by enzyme-linked immunosorbent assay (ELISA).	I month post dose 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with anti-Diphtheria antibody concentrations ≥ 0.01 IU/mL and ≥ 0.1 IU/mL International Units (IU)/mL	Anti-Diphtheria antibodies will be measured by a toxin neutralization test	Day 0 Pre-vaccination
Number of participants with anti-Hepatitis B antibody concentrations ≥ 10 mIU/mL international unit (IU)/mL	Anti-Hepatitis B antibodies will be measured by the commercially available VITROS ECi/ECiQ Immunodiagnostic System using chemiluminescence detection technology	Day 0 Pre-vaccination
Number of participants with anti Diphtheria antibody concentrations ≥ 0.1 IU/mL International Units (IU)/mL	Anti-Diphtheria antibodies will be measured by a toxin neutralization test	1 month post third vaccination
Number of participants reporting solicited injection site and solicited systemic reactions, unsolicited adverse events, and serious adverse events following vaccination with either DTaP-IPV-Hep B-PRP~T combined vaccine or Pentaxim™ and Euvax B® vaccine	Solicited injection site reactions Tenderness, Erythema, and Swelling. Solicited systemic reactions Fever (temperature), Vomiting, Crying abnormal, Drowsiness, Appetite loss, and Irritability.	Day 0 and up to Day 180 post-vaccination
Number of participants with response to vaccine Pertussis toxoid (PT) and Filamentous Haemagglutinin (FHA) antigens	Vaccine response defined as: Post-dose 3 anti-PT and anti-FHA antibody concentrations in ELISA units (EU)/mL ≥ 4 x Lower Limit of Quantitation (LLOQ) if pre-vaccination concentration is < 4 x LLOQ or ≥ pre-vaccination concentration if pre-vaccination concentrations ≥ 4 x LLOQ	1 month post third vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: March 20, 2014
• First Submitted That Met QC Criteria: March 20, 2014
• First Posted (Estimate): March 24, 2014

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Hepatitis B; Pertussis; Diphtheria; Tetanus; Haemophilus influenzae type b infection; DTaP-IPV-Hep - PRP-T vaccine
• Additional Relevant MeSH Terms: Digestive System Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Neuromuscular Diseases; Central Nervous System Infections; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Enterovirus Infections; Picornaviridae Infections; Spinal Cord Diseases; Clostridium Infections; Corynebacterium Infections; Myelitis; Pasteurellaceae Infections; Hepatitis B; Whooping Cough; Hepatitis; Tetanus; Diphtheria; Poliomyelitis; Haemophilus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: A3L31; U1111-1127-6896 (Other Identifier: WHO)