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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatitis B, Polio, Diphtheria, Pertussis, Haemophilus Influenzae Type b

Intervention / Treatment
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* Biological: DTaP-IPV-HB-PRP T
* Biological: CombAct-HIB®
* Biological: Engerix B® Pediatric


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 3 Days

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: DTaP-IPV-Hep B-PRP-T<br> | Biological: DTaP-IPV-HB-PRP T<br>* 0.5 mL, Intramuscular (IM)<br>|
| Experimental: Group 2: CombAct-HIB™ + OPV<br> | Biological: CombAct-HIB®<br>* 0.5 mL, IM<br>|
| Active Comparator: Group 3: DTaP-IPV-Hep B-PRP-T (ENGERIX B™ at birth)<br> | Biological: Engerix B® Pediatric<br>* 0.5 mL, IM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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). | 1 month post-Dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | 1 month post-Dose 3 | 
| 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) | 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. | Day 42 before Dose 1 and 1 month post-Dose 3 | 
| 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 | 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. | Day 540 pre-booster and Day 570 post-booster | 
| 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 | 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. | Day 540 pre-booster and Day 570, post-booster | 
| 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). | 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. | Day 0 up to Day 7 post each dose | 
| 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) | 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. | Day 0 up to 7 post-booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, Polio, Diphtheria, Pertussis, H. influenzae type b