Study of DTwP-HepB-Hib-IPV (SHAN6™) Vaccine Administered Concomitantly With Routine Pediatric Vaccines to Healthy Infants and Toddlers in Thailand

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the non-inferiority of the SHAN6™ vaccine to the licensed SHAN5™ given with bOPV and IPV vaccines when coadministered with PCV and ORV Secondary Objective: To describe the immunogenicity profile of the SHAN6™ vaccine 3-dose primary infant vaccination and that of the control vaccines (SHAN5™ given with bOPV and IPV) To describe the immune response to co-administered ORV-1 (Rotarix™) in a subset of participants from each group To describe the immune response to co-administered PCV-13 (Prevnar 13®) in a subset of participants from each group To describe the persistence of the antibodies against SHAN6™ antigens following a 3-dose primary series of SHAN6™ or SHAN5™ given with bOPV and IPV To describe the immunogenicity profile of SHAN6™ 28 days after the single booster dose of SHAN6™ To describe the safety profile of the SHAN6™ vaccine and the control vaccines (SHAN5™ given with bOPV and IPV), when administered concomitantly with routine pediatric vaccines

Detailed Description
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The duration of each participant's active participation in the study will be approximately 14-17 months (416-506 days) in addition to the 2 MedDRA terms: Polio immunisation 10054175 Hepatitis B immunisation 10054181 Haemophilus influenzae type B immunisation 10069533 Tetanus immunisation 10054131 Rotavirus immunisation 10076886 Pneumococcal immunisation 10069578

Official Title
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Immunogenicity and Safety of a DTwP-HepB-Hib-IPV (Shan6™) Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in Thailand

Conditions
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Pertussis Immunisation, Diphtheria Immunisation, Polio Immunisation, Hepatitis B Immunisation, Haemophilus Influenzae Type B Immunisation, Tetanus Immunisation, Rotavirus Immunisation, Pneumococcal Immunisation

Intervention / Treatment
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* Biological: DTwP-HepB-Hib-IPV hexavalent vaccine (Diphtheria toxoid, Tetanus toxoid, whole cell pertussis, Hepatitis B surface antigen (HBsAg), Haemophilus influenzae type b, inactivated poliovirus)
* Biological: DTwP-HepB-Hib pentavalent vaccine (Diphtheria toxoid, Tetanus toxoid, whole cell pertussis, Hepatitis B surface antigen (HBsAg), Haemophilus influenzae type b)
* Biological: Inactivated Poliomyelitis Vaccine
* Biological: Poliomyelitis Vaccine bivalent types 1 and 3
* Biological: Human Rotavirus, live attenuated
* Biological: Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Aged ≥ 2 months (age range of 8 weeks <12 weeks) on the day of the first vaccination Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg or medically stable prematurely born infants (born after a gestational period of 27-36 weeks) Infants who have received the birth dose of Bacille Calmette-Guérin vaccine (BCG) at least 4 weeks before the first trial vaccination Participant and parent(s)/legally acceptable representative(s) are able to attend all scheduled visits and comply with all study procedures Exclusion criteria: Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) 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 or planned receipt of any vaccine within the period of 4 weeks before to 4 weeks after each trial vaccination, except for oral polio vaccine (OPV) and influenza vaccination. OPV may be received any time during the study while influenza vaccination may be received at a gap of at least 2 weeks before or 2 weeks after any study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B (except the dose of Hep B vaccine given at birth or at least 4 weeks before the first trial vaccination), Haemophilus influenzae type b, poliomyelitis (except OPV), rotavirus, and Streptococcus pneumoniae with either the trial vaccines or another vaccine Receipt of immune globulins, blood or blood-derived products since birth 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 at ≥ 0.5 mg/kg/day for more than 2 consecutive weeks since birth) Known personal or maternal history of Human Immunodeficiency Virus (HIV), hepatitis B (HBsAg positive), or hepatitis C (hepatitis C virus [HCV] ribonucleic acid [RNA] positive) Individuals with blood dyscrasias, leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b, rotavirus, or pneumococcal infection(s) confirmed either clinically, serologically, or microbiologically History of any neurologic disorders, including encephalopathy, seizures (febrile and non-febrile) and progressive neurologic disorders History of intussusception In an emergency setting, or hospitalized Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances Thrombocytopenia, as reported by the parent/legally acceptable representative, contraindicating intramuscular vaccination in the Investigator's opinion Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion Chronic illness that, in the Investigator's opinion, is at a stage where it might interfere with trial conduct or completion Any condition which, in the Investigator's opinion, might interfere with the evaluation of the study objectives Moderate or severe acute illness/infection (according to the Investigator's judgment) on the day of vaccination or febrile illness (axillary temperature ≥ 38.0 C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw Identified as a natural or adopted child of the Investigator, relatives or employee with direct involvement in the proposed study The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 8 Weeks
Maximum Age: 11 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A - Intervention regimen<br>SHAN6™ + routine pediatric vaccines pneumococcal 13-valent conjugate vaccine [PCV] [Prevnar 13®] and oral rotavirus vaccine [ORV-1] [Rotarix™] at age of 2, 4 months; SHAN6™ + Prevnar 13® at age of 6 months; SHAN6™ administered alone as a booster dose at age of 15-18 months | Biological: DTwP-HepB-Hib-IPV hexavalent vaccine (Diphtheria toxoid, Tetanus toxoid, whole cell pertussis, Hepatitis B surface antigen (HBsAg), Haemophilus influenzae type b, inactivated poliovirus)<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: SHAN6™;Biological: Human Rotavirus, live attenuated<br>* Pharmaceutical form:Oral suspension Route of administration: Oral<br>* Other names: Rotarix™;Biological: Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Prevnar 13®, PCV-13;|
| Active Comparator: Group B - Control regimen<br>SHAN5™ + bivalent oral polio vaccine (bOPV), co-administered with Prevnar 13® and Rotarix™ at 2, 4 months of age and with inactivated polio vaccine [IPV] at 4 months of age; SHAN5™ + bOPV, co-administered with Prevnar 13® at 6 months of age SHAN6™ administered alone as a booster dose at 15-18 months of age | Biological: DTwP-HepB-Hib-IPV hexavalent vaccine (Diphtheria toxoid, Tetanus toxoid, whole cell pertussis, Hepatitis B surface antigen (HBsAg), Haemophilus influenzae type b, inactivated poliovirus)<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: SHAN6™;Biological: DTwP-HepB-Hib pentavalent vaccine (Diphtheria toxoid, Tetanus toxoid, whole cell pertussis, Hepatitis B surface antigen (HBsAg), Haemophilus influenzae type b)<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: SHAN5™;Biological: Inactivated Poliomyelitis Vaccine<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: IMOVAX Polio;Biological: Poliomyelitis Vaccine bivalent types 1 and 3<br>* Pharmaceutical form:Oral suspension Route of administration: Oral<br>Biological: Human Rotavirus, live attenuated<br>* Pharmaceutical form:Oral suspension Route of administration: Oral<br>* Other names: Rotarix™;Biological: Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)<br>* Pharmaceutical form:Suspension for injection Route of administration: Intramuscular<br>* Other names: Prevnar 13®, PCV-13;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with antibodies (Ab) above predefined threshold against diphtheria (D), tetanus (T), hepatitis B (Hep B), Haemophilus influenzae type b (Hib) and poliovirus (Polio) antigens | Ab titers against D, T, Hep B, Hib and Polio antigens will be measured Threshold values will be considered | 28 days after the third dose (Day 148) | 
| Adjusted Geometric Mean Concentrations (aGMCs) of Ab against pertussis antigens | Ab against pertussis antigens will be measured | 28 days after the third dose (Day 148) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Ab titers above predefined thresholds against each antigen diphtheria, tetanus, hepatitis B, Haemophilus influenzae type b and poliovirus antigens | Ab titers against D, T, Hep B, Hib and polio antigens will be measured Threshold values will be considered | At baseline (Day 0) and 28 days after the third dose (Day 148) | 
| Number of participants with a vaccine response for pertussis antigens | Pertussis antigens vaccine response Threshold values will be considered | At baseline (Day 0) and 28 days after the third dose (Day 148) | 
| Pertussis antigens vaccine seroconversion | Ab against pertussis antigens will be measured | At baseline (Day 0) and 28 days after the third dose (Day 148) | 
| Geometric Mean Concentrations Ratios (GMCRs) of Ab against all the antigens, including anti-rotavirus and anti-S. pneumoniae in a subset of participants | Ab concentrations against all the antigens, including anti-rotavirus and anti-S. pneumoniae for a subset of participants, will be measured The ratio calculated will be: (post dose 3/pre-primary) | At baseline (Day 0) and 28 days after the third dose (Day 148) | 
| GMCs of Ab against each antigen, including anti-rotavirus and anti-pneumococcal serotypes, in a subset of participants | Ab concentrations against each antigen, including anti rotavirus and anti pneumococcal serotypes for a subset of participants, will be measured | At baseline (Day 0) and 28 days after the third dose (Day 148) | 
| Number of participants with anti-rotavirus Ab titers above predefined thresholds in a subset of participants | Ab against rotavirus will be measured in a subset of participants Threshold values will be considered | At baseline (Day 0) and 28 days after the third dose (Day 148) | 
| Number of participants with anti-pneumococcal Ab titers above predefined thresholds in a subset of participants | Anti-pneumococcal Ab will be measured in a subset of participants Threshold values will be considered | At baseline (Day 0) and 28 days after the third dose (Day 148) | 
| Number of participants with Ab titers above predefined threshold against diphtheria, tetanus, hepatitis B, Haemophilus influenzae type b and poliovirus antigens | Ab against D, T, Hep B, Hib and polio antigens will be measured Threshold values will be considered | Before and 28 days after the booster dose (at Day 388-478 and Day 416-506) | 
| Number of participants with a booster response for pertussis antigens | Pertussis antigens booster response Threshold values will be considered | Before and 28 days after the booster dose (at Day 388-478 and Day 416-506) | 
| Pertussis antigens vaccine seroconversion | Ab against pertussis antigens will be measured | Before and 28 days after the booster dose (at Day 388-478 and Day 416-506) | 
| GMCRs of Ab against all the antigens | Ab concentrations against all the antigens will be measured The ratio calculated will be: (post booster/pre-booster) | Before and 28 days after the booster dose (at Day 388-478 and Day 416-506) | 
| GMCs of Ab against each antigen | Ab concentrations against each antigen will be measured | Before and 28 days after the booster dose (at Day 388-478 and Day 416-506) | 
| aGMCs of Ab against pertussis antigens | Ab against pertussis antigens will be measured, adjusted for baseline value | Before and 28 days after the booster dose (at Day 388-478 and Day 416-506) | 
| Number of participants reporting immediate systemic adverse events (AEs) | Unsolicited (spontaneously reported) systemic AEs | Within 30 minutes post-vaccination | 
| Number of participants reporting solicited injection site and systemic reactions | Solicited injection site reactions: - tenderness, erythema and site swelling Solicited systemic reactions: - fever, vomiting, crying abnormal, drowsiness, appetite lost and irritability | Up to 7 days post-vaccination | 
| Number of participants reporting unsolicited non-serious AEs | Unsolicited non-serious AEs | Up to 28 days post-vaccination | 
| Number of participants reporting serious adverse events (SAEs) | SAEs | Up to Day 416-506 |