Safety of DTaP-IPV-Hep B-PRP T Combined Vaccine Compared to Tritanrix-HepB/Hib™ and OPV Given at Age 2, 4, and 6 Months.

Study Overview
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Brief Summary
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To demonstrate that DTaP-IPV-HB-PRP T combined vaccine does not induce a higher incidence rate of high fever than Tritanrix-HepB/Hib™ and Oral Polio Vaccine (OPV) after any of the three vaccinations at 2, 4, and 6 months of age for each subject. To evaluate the overall safety in terms of: Any solicited adverse reactions in the first 7 days after each injection, Any adverse events and reactions in the first 30 days after each injection, Any serious adverse events during the trial. Immunogenicity: To document the immune response to Hepatitis B antigen of the three batches of the investigational DTaP-IPV-HB-PRP T vaccine.

Official Title
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Large Scale Safety Study of a DTaP-IPV-Hep B-PRP T Combined Vaccine, in Comparison to Tritanrix-Hep B/Hib™ and OPV Administered at 2, 4, and 6 Months of Age in Latin American Infants

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

Intervention / Treatment
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* Biological: DTaP-IPV-HB-PRP T
* Biological: Tritanrix-HepB/Hib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2 months old infants on the day of inclusion Born at full term of pregnancy (≥ 37 weeks) with a birth weight ≥ 2.5 kg Informed consent form signed by one or both parents or by the legally acceptable representative and 1 or 2 independent witnesses Able to attend all scheduled visits and to comply with all trial procedures Has complied with the national immunization calendar (BCG for both countries) for the first 2 months of life. Exclusion Criteria: Participation in another clinical trial in the 4 weeks preceding the first trial vaccination Planned participation in another clinical trial during the present trial period Congenital or acquired immunodeficiency, immunosuppressive therapy such as long-term systemic corticosteroids therapy Subjects with congenital or acquired immunodeficiency in the child's surrounding 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 Chronic illness at a stage that could interfere with trial conduct or completion Blood or blood-derived products received since birth Any vaccination in the 4 weeks preceding the first trial vaccination Vaccination planned in the 4 weeks following the trial vaccination Documented history of pertussis, tetanus, diphtheria, poliomyelitis, Haemophilus influenzae type b or hepatitis B infection(s) (confirmed either clinically, serologically or microbiologically) Mother known as seropositive for HIV or Hepatitis C, or known carrier of Hepatitis B surface antigen Previous vaccination against pertussis, tetanus, diphtheria, poliomyelitis, or Haemophilus influenzae type b infection(s) Coagulopathy, thrombocytopenia or a bleeding disorder contraindicating IM vaccination History of seizures Febrile or acute illness on the day of inclusion.

Ages Eligible for Study
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Minimum Age: 50 Days
Maximum Age: 71 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: Single


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>|
| Active Comparator: Group 2: Tritanrix-Hep B/Hib™+OPV<br> | Biological: Tritanrix-HepB/Hib<br>* 0.5 mL, Intramuscular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With High Fever Observed After Either DTaP-IPV-Hep B-PRP T or Tritanrix Hep B/Hib™ + Placebo or Tritanrix-Hep B/Hib™ + Placebo Injection. | High fever was defined as rectal temperature equivalent to ≥ 39.6ºC. | Day 0 up to Day 7 post-injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Anti Hepatitis B Antibodies Following Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine + Placebo or Tritanrix-Hep B/Hib™ + Placebo | Anti-hepatitis B (Hep B) antibodies were measured by automated enhanced chemiluminescence assay. | Day 30 post-dose 3 | 
| Percentage of Participants Reaching Seroprotection Threshold Following Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine + Placebo or Tritanrix-Hep B/Hib™ + Placebo | Anti hepatitis B (Hep B) antibodies were measured by automated enhanced chemiluminescence assay. Two Seroprotection thresholds were defined: a titer ≥ 10 mIU/mL and ≥ 100 mIU/mL, respectively. | Day 30 post-dose 3 | 
| Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Each Vaccination | Solicited Injection Site Reactions: Pain, Erythema, Swelling. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, Irritability. Severe solicited reactions were defined as follows: Pain, cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling, ≥5 cm; Fever ≥39.6 ºC; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying, >3 hours; Somnolence, sleeping most of the time or difficulty to wake up; Anorexia, refuses ≥3 feeds or refuses most feeds; Irritability, inconsolable. | Day 0 up to Day 7 Post-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diphtheria, Tetanus, Pertussis, Recombinant Hepatitis B, Poliomyelitis, Haemophilus influenzae type b, Tetanus protein