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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Diphtheria, Tetanus, Whooping Cough, Hepatitis B, Poliomyelitis, Invasive Hib Infections

Intervention / Treatment
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* Biological: Hexaxim™: DTaP-IPV-Hep B-PRP T combined vaccine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 8 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>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<br>* 0.5 mL, Intramuscular<br>* Other names: Hexaxim™;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diphtheria, Tetanus, Whooping Cough, Hepatitis B, Poliomyelitis, DTaP IPV-Hep B-PRP T combined vaccine (Hexaxim™)