Study of DTaP-IPV-Hep B-PRP~T Combined Vaccine in Indian Infants Previously Given a Dose of Hepatitis B Vaccine at Birth

Immunogenicity and Safety of Sanofi Pasteur's DTaP-IPV-Hep B-PRP-T Combined Vaccine Given at 6, 10 and 14 Weeks of Age in Infants From India Who Previously Received a Dose of Hepatitis B Vaccine at Birth

The purpose of this study is to describe the immunogenicity and safety of a novel DTaP- IPV- Hep B-PRT~T fully liquid combined hexavalent vaccine (Hexaxim™) administered at 6, 10 and 14 weeks of age in infants born to mothers documented to be serum anti-hepatitis B surface antigen (HBsAg) serology negative in India.

Primary Objective:

• To evaluate the immunogenicity of the study vaccine in terms of seroprotection [diphtheria toxoid, tetanus toxoid, poliovirus types 1, 2 and 3, Haemophilus influenzae type b (Hib) polysaccharide (PRP), hepatitis B (Hep B)] and vaccine response for pertussis antigens [pertussis toxoid (PT) and filamentous haemagglutinin (FHA)] one month after the third dose.

Secondary Objectives:

• To further describe the immunogenicity of the study vaccine, before the first dose and one month after the third dose.
• To describe the safety after each and any doses of the study vaccine.

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Whooping Cough; Tetanus; Diphtheria; Poliomyelitis; Invasive Hib Infections
• Intervention / Treatment: Biological: Hexaxim™: DTaP-IPV-Hep B-PRP~T combined vaccine

Detailed Description

All participants will receive a total 4 doses of Hep B, i.e. one dose of Hep B monovalent vaccine given at birth followed by 3 doses of Sanofi Pasteur's hexavalent vaccine given at 6, 10 and 14 weeks of age in the context of the study. Participants and parents will attend four clinic visits; the expected participation in the study is approximately 3 months.

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Pune, India, 411043
  • Punjab
    • Ludhiana, Punjab, India, 141008

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged between 42-56 days (6 to 8 weeks) on the day of inclusion
• Born at full term of pregnancy (≥37 weeks) and with a birth weight ≥2.5 kg
• Informed consent form signed by the parent(s) or any other legally acceptable representative
• Subject 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 maternal blood sample performed during last trimester of pregnancy available)
• Have received one documented dose of Hep B vaccine and oral poliovirus vaccine (OPV) from birth as per national recommendations.

Exclusion Criteria:

• Participation in another clinical trial 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 the first trial vaccination (except Bacillus Calmette-Guerin [BCG] vaccine) or planned receipt of any other vaccine within the period from 8 days before to 8 days after each subsequent trial vaccination
• Previous vaccination against the diphtheria, tetanus, pertussis, poliomyelitis (expect the birth dose of OPV as per national recommendations) and hepatitis B (except the birth dose of Hep B vaccine) diseases or Hib infection with 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)
• History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Hib infections (confirmed either clinically, serologically or microbiologically)
• Known personal or maternal history of Human Immunodeficiency Virus (HIV) or hepatitis C seropositivity
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the trial vaccine or a vaccine containing 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 (axillary temperature ≥38°C) on the day of inclusion (a prospective subject 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, relatives 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group; Participants will receive Sanofi Pasteur's DTaP-IPV-Hep B-PRP~T combined vaccine (investigational vaccine) at 6, 10 and 14 weeks of age.	Biological: Hexaxim™: DTaP-IPV-Hep B-PRP~T combined vaccine; 0.5 mL, Intramuscular; Other Names: Hexaxim™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroprotection After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Diphtheria antibodies were measured by a toxin neutralization test, tetanus antibodies by an enzyme-linked immunosorbent assay (ELISA), Haemophilus influenzae type b polysaccharide (PRP) antibodies by Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hepatitis B (Hep B) antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System. Description of seroprotection: Diphtheria and Tetanus antibody concentrations ≥0.01 International Units (IU)/mL; Poliovirus 1, 2, and 3 titers ≥8 (1/dilution); Hep B concentrations ≥10 mIU/mL, and PRP ≥0.15 µg/mL.	Pre-dose 1 to one month post-dose 3
Percentage of Participants With Vaccine Response After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibodies were measured with an ELISA. Vaccine response was defined as percentage of participants with post-dose 3 anti-PT and anti-FHA antibody concentrations in ELISA units (EU)/mL ≥ 4 x Lower Limit of Quantification (LLOQ) if pre-vaccination concentration was < 4 x LLOQ or ≥ pre-vaccination concentration if pre-vaccination concentrations ≥ 4 x LLOQ.	Pre-dose 1 to one month post-dose 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroprotection Before and After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Diphtheria antibodies were measured by a toxin neutralization test, tetanus antibodies by an enzyme-linked immunosorbent assay (ELISA), Haemophilus influenzae type b polysaccharide (PRP) antibodies by Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hepatitis B (Hep B) antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System. Description of seroprotection: Diphtheria and Tetanus antibody concentrations ≥0.01 International Units (IU)/mL; Poliovirus 1, 2, and 3 titers ≥8 (1/dilution); Hep B concentrations ≥10 mIU/mL, and PRP ≥0.15 µg/mL.	Pre-dose 1 to one month post-dose 3
Geometric Mean Titers of Antibodies Against Vaccine Antigens After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine After a Documented Dose of an Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Diphtheria antibodies were measured by a toxin neutralization test, tetanus, PT, and FHA antibodies by an ELISA, PRP antibodies by a Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hep B antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.	Pre-dose 1 to one month post-dose 3
Geometric Mean Titer Ratios of Antibodies Against Vaccine Antigens After Vaccinations With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine After a Documented Dose of Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth	Diphtheria antibodies were measured by a toxin neutralization test, PT and FHA antibodies by an ELISA, and Hep B antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.	Pre-dose 1 to one month post-dose 3
Percentage of Participants Reporting Solicited Injection-site or Systemic Reaction After Each Vaccination With Sanofi Pasteur's DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of Oral Poliovirus and Recombinant Hep B Vaccine at Birth	Injection-site reactions: Tenderness, Erythema, and Swelling. Systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3 Injection site reactions: Tenderness, Cries when injected limb is moved, or reduced movement of injected limb; Erythema and Swelling, ≥50 mm. Grade 3 Systemic reactions: Fever, >39.5°C or >103.1°F; Vomiting, ≥6 episodes/24 hours or requires parenteral hydration; Crying abnormal, >3 hours; Drowsiness, Sleeping most of the time/difficult to wake up; Appetite lost, Refuses ≥3 or most feeds/meals; Irritability, Inconsolable.	Within 7 days after each vaccine injection

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: February 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: September 18, 2013
• First Submitted That Met QC Criteria: September 18, 2013
• First Posted (Estimate): September 23, 2013

Study Record Updates

• Last Update Posted (Estimate): October 20, 2015
• Last Update Submitted That Met QC Criteria: September 29, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Hepatitis B; Diphtheria; Tetanus; Poliomyelitis; Whooping Cough; DTaP IPV-Hep B-PRP~T combined vaccine (Hexaxim™)
• 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; Hepatitis B; Whooping Cough; Hepatitis; Hepatitis A; Tetanus; Diphtheria; Poliomyelitis
• Other Study ID Numbers: A3L33; U1111-1127-6936 (Other Identifier: WHO); CTRI/2013/09/003997 (Registry Identifier: Clinical Trial Registry India)