A Study of DTaP-IPV-Hep B-PRP-T Vaccine Given With Prevenar™ and Rotarix™ in Healthy Latin American Infants

Study Overview
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Brief Summary
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The purpose of this study is to generate immunogenicity and safety data of an investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine compared to a control vaccine, Infanrix hexa™ when given along with Prevenar™ and Rotarix™ vaccines. Primary Objectives: To demonstrate the equivalence of immunogenicity of 3 lots of DTaP-IPV-Hep B-PRP-T vaccine 1 month after a 3-dose primary series (2, 4 and 6 months) when given with Prevenar™ and Rotarix™, in terms of immunoresponses. To demonstrate the non-inferiority of the hexavalent DTaP-IPV-Hep B-PRP-T vaccine to the licensed hexavalent Infanrix hexa vaccine when given with Prevenar™ and Rotarix™. Secondary Objectives: To describe in each group the immunogenicity parameters for all antigens for each vaccine To assess the safety profile in terms of solicited and unsolicited adverse events and serious adverse events in each group for each vaccine.

Detailed Description
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Each participant will receive 3 doses of 1 of 3 lots of the investigational hexavalent vaccine or the control vaccine, Infanrix hexa™, administered with Prevenar™ at 2, 4, and 6 months of age and Rotarix™ at 2 and 4 months of age. All participants will be monitored for safety for 6 months after the last injection of the primary vaccination series.

Official Title
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Lot-to-Lot Consistency Study of DTaP-IPV-Hep B-PRP-T Vaccine Administered at 2-4-6 Months of Age in Healthy Latin American Infants Concomitantly With Prevenar™ and Rotarix™

Conditions
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Diphtheria, Tetanus, Whooping Cough, Hepatitis B, Poliomyelitis

Intervention / Treatment
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* Biological: DTaP-IPV-Hep B-PRP-T Vaccine
* Biological: DTaP-IPV-Hep B-PRP-T Vaccine
* Biological: DTaP-IPV-Hep B-PRP-T Vaccine
* Biological: DTaP-Hep B-IPV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Two month old infants (55 to 65 days old) 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 as per local requirements. Able to attend all scheduled visits and to comply with all trial procedures. Received Hepatitis B and Bacille de Calmette-Guérin (BCG) vaccines between birth and one month of life in agreement with the national immunization calendar. 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. Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy, or long-term systemic corticosteroid therapy. 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. Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator. Blood or blood-derived products received since birth that might interfere with the assessment of the immune response. Any vaccination before trial vaccination (except Hepatitis B and Bacille de Calmette Guérin given at birth). Any planned vaccination until 1 month after the last trial vaccination (except the study vaccines, rotavirus and pneumococcal conjugated vaccines). Documented history of pertussis, tetanus, diphtheria, poliomyelitis, Haemophilus influenzae type b or Hepatitis B infection(s) (confirmed either clinically, serologically or microbiologically). Previous vaccination against pertussis, tetanus, diphtheria, poliomyelitis, or Haemophilus influenzae type b infections. Known personal or maternal history of Human Immunodeficiency Virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C seropositivity. Known coagulopathy, thrombocytopenia or a bleeding disorder preceding inclusion contraindicating intramuscular (IM) vaccination. History of seizures or encephalopathy. Febrile illness (temperature ≥ 38.0°C), or moderate or severe acute illness/infection on the day of inclusion, according to the Investigator judgment.

Ages Eligible for Study
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Minimum Age: 55 Days
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: DTaP-IPV-Hep B-PRP-T (Lot A)<br> | Biological: DTaP-IPV-Hep B-PRP-T Vaccine<br>* 0.5 mL, Intramuscular<br>|
| Experimental: Group 2: DTaP-IPV-Hep B-PRP-T (Lot B)<br> | Biological: DTaP-IPV-Hep B-PRP-T Vaccine<br>* 0.5 mL, Intramuscular<br>|
| Experimental: Group 3: DTaP-IPV-Hep B-PRP-T (Lot C)<br> | Biological: DTaP-IPV-Hep B-PRP-T Vaccine<br>* 0.5 mL, Intramuscular<br>|
| Active Comparator: Group 4: Active Control<br> | Biological: DTaP-Hep B-IPV vaccine<br>* 0.5 mL, Intramuscular<br>* Other names: Infanrix hexa™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Anti-Hepatitis B Before and After 3 Dose Primary Vaccination With Either DTaP-IPV-Hep B-PRP T Batch A, B, or C, or Infanrix Hexa™ | Antibodies against Hepatitis B (Hep B) were measured by chemiluminescence detection. | Day 0 (pre-vaccination) Dose 1 and 30 days post-vaccination | 
| Number of Participants With Seroprotection or Vaccine Response After Vaccination With Either DTaP-IPV-Hep B-PRP T or Infanrix Hexa Vaccine | Seroprotection was defined as titers ≥ 0.01 IU/mL for Diphtheria (D) and Tetanus (T); ≥ 10 IU/mL for Hep B; ≥ 0.15 µg/mL for PRP, and ≥ 8 (1/dil) for Poliovirus. Vaccine response for PT and FHA were defined as a titer ≥ lower limit of quantitation (LLOQ) in initially seronegative participants, or at least persistence (post-vaccination titer ≥ pre-vaccination titer) in initially seropositive subjects (titer ≥ LLOQ). | 30 Days post-dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Antibodies After Vaccination With Either DTaP-IPV-Hep B-PRP T or Infanrix Hexa Vaccine | Antibodies were measured by toxin neutralization test for Diphtheria (D); enzyme-linked immunosorbent assay (ELISA) for Tetanus (T), Pertussis toxoid (PT), and Filamentous hemagglutinin (FHA); neutralization assay for Poliovirus types 1, 2, and 3; chemiluminescence detection for Hepatitis B (Hep B), and Farr type radioimmunoassay for Haemophilus influenza type b (PRP). | Day 0 (pre-vaccination) and 30 days post-dose 3 | 
| Number of Participants Reporting at Least One Solicited Injection Site (Study Vaccine) or Systemic Reactions After Vaccination With Either DTaP-IPV-Hep B-PRP T or Infanrix Hexa Vaccine | Solicited Injection Site Reactions: Pain, Erythema, and Swelling. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia,and Irritability. Grade 3 was defined as: Pain, cries when injected limb is moved or movement of the limb is reduced; Erythema and Swelling, ≥ 5 cm; Pyrexia, (Temperature) ≥ 39.6°C; Vomiting, ≥ 6 episodes/24 hours or requiring parenteral hydration; Crying, > 3 hours; Somnolence, sleeping most of time or difficult to wake up; Anorexia, refuses ≥ 3 feed/meals or refuses most feeds/meals; and Irritability, inconsolable. | Day 0 up to 7 after each dose | 
| Number of Participants Reporting at Least One Solicited Injection Site Reaction at the Prevenar Injection Site After Vaccination With Either DTaP-IPV-Hep B-PRP T or Infanrix Hexa™ Vaccine | Solicited Injection Site Reactions: Pain, Erythema, and Swelling. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, and Irritability. Grade 3 was defined as: Pain, cries when injected limb is moved or movement of the limb is reduced; Erythema and Swelling, ≥ 5 cm; Pyrexia (Temperature), ≥ 39.6ºC; Vomiting, ≥ 6 episodes/24 hours or requiring parenteral hydration; Crying, > 3 hours; Somnolence, sleeping most of time or difficult to wake up; Anorexia, refuses ≥ 3 feed/meals or refuses most feeds/meals; and Irritability, inconsolable. | Day 0 up to 7 post each vaccination | 

 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, Diphtheria-Tetanus-acellular Pertussis Vaccines