Spanish Mixed HEXA/PENTA/HEXA Schedule (V419-010)

Study Overview
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Brief Summary
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To evaluate the immune response and the safety of a primary series schedule that includes V419 (PR5I) at 2 and 6 months of age and Pediacel at 4 months of age Primary objectives To demonstrate that the mixed schedule induces acceptable responses for Hepatitis B (HB) one month after completion of the mixed schedule To demonstrate that the mixed schedule induces acceptable responses for Haemophilus influenzae type b (Hib) one month after completion of the mixed schedule Secondary objectives To describe the antibody response to all PR5I antigens one month after completion of the mixed schedule To describe the antibody response to meningococcal serogroup C (MCC) conjugate vaccine one month after the second dose of MenC vaccine To describe the safety profile after each dose of study vaccines administered

Official Title
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A Phase 3 Open-label Study to Evaluate the Immunogenicity and Safety of a Mixed (HEXA/PENTA/HEXA) Primary Series Schedule That Includes V419 (PR5I) at 2 and 6 Months of Age and Pediacel at 4 Months of Age.

Conditions
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Neisseria Meningitidis, Bacterial Infections, Virus Diseases

Intervention / Treatment
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* Biological: PR5I
* Biological: Pediacel®
* Biological: NeisVac-C®
* Biological: RotaTeq®
* Biological: Prevenar 13®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infant 46 to 74 days (both inclusive) Documented receipt of only one dose of monovalent hepatitis B vaccine within the 3 days after birth Parent(s)/legal representative able to comply with the study procedures Exclusion Criteria: Participation in any study with an investigational compound or device since birth History of congenital or acquired immunodeficiency Chronic illness that could interfere with study conduct or completion Hypersensitivity to any of the study vaccines components or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines Contraindication to Pediacel®, NeisVac-C®, Prevenar 13®, and RotaTeq® History or maternal history of HBsAg seropositivity Coagulation disorder that contraindicate intramuscular injection History of vaccination with a Haemophilus influenzae type b conjugate, diphtheria, tetanus, pertussis (acelullar or whole-cell), poliovirus, meningococcal serogroup C conjugate, pneumococcal conjugate containing vaccine(s) History of hepatitis B, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, poliomyelitis, or serogroup C meningococcal infection Receipt of immune globulin, blood or blood-derived products since birth Receipt of systemic corticosteroids for more than 14 consecutive days within one month of the study start Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study

Ages Eligible for Study
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Minimum Age: 46 Days
Maximum Age: 76 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PR5I (V1); Pediacel® (V2); PR5I (V3)<br>[Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by intramuscular (IM) injection + oral RotaTeq®, given at 2 months of age. [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age. [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age. | Biological: PR5I<br>* Hexavalent PR5I vaccine (DTaP-HB-IPV-Hib = Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed [DTaP], Hepatitis B [HB; Recombinant DNA], Inactivated Poliovirus [IPV], and Haemophilus influenzae type b [Hib] conjugate vaccine [adsorbed]) at 0.5 mL for IM injection (left upper thigh) at 2 and 6 months of age.<br>* Other names: DTaP-HB-IPV-Hib;Biological: Pediacel®<br>* Pentavalent Pediacel® vaccine (DTaP-IPV-Hib = Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed [DTaP], Inactivated Poliovirus [IPV], and Haemophilus influenzae type b [Hib] conjugate vaccine [adsorbed]) at 0.5 mL for IM injection (left upper thigh) at 4 months of age.<br>* Other names: DTaP-IPV-Hib;Biological: NeisVac-C®<br>* Meningococcal group C (MCC) polysaccharide conjugate vaccine (adsorbed) at 0.5 mL for IM injection (right upper thigh) at 2 and 4 months of age.<br>Biological: RotaTeq®<br>* Human-bovine rotavirus reassortants (live) vaccine 2 mL oral administration at 2, 4 and 6 months of age. RotaTeq® administered prior to any other vaccine administration to avoid having the infant participants spit up the RotaTeq® when crying.<br>Biological: Prevenar 13®<br>* Pneumococcal polysaccharide conjugate vaccine [PCV; 13-valent, adsorbed]) at 0.5 mL for IM injection (right upper thigh) at 2 and 4 months of age.<br>* Other names: PCV-13;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Anti-Hepatitis B Surface Antigen (HBsAg) Antibody Titer ≥10 mIU/mL | The percentage of participants with an anti-HBsAg antibody titer ≥10 mill-International Units/mL (mIU/mL) was assessed. Participant serum samples were collected for analysis with an enhanced chemiluminescence assay to determine the concentration of antibodies to HBsAg. | Month 5 (one month after receiving Vaccination 3) | 
| Percentage of Participants With an Anti-Polyribosylribitol Phosphate (PRP) Antibody Titer ≥0.15 µg/mL | The percentage of participants with an anti-Polyribosylribitol Phosphate (PRP) antibody titer ≥0.15 µg/mL was assessed. Participant serum samples were collected for analysis by radioimmunoassay to determine the concentration of antibodies to PRP, a Haemophilus influenzae type b (Hib) capsular polysaccharide. | Month 5 (one month after receiving Vaccination 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration of Antibodies to Hepatitis B Surface Antigen (HBsAg) | Participant serum samples were collected for analysis with an enhanced chemiluminescence assay to determine the geometric mean concentration of antibodies to Hepatitis B Surface Antigen (HBsAg). The unit of measure is milli International Units/mL (mIU/mL). | Month 5 (one month after receiving Vaccination 3) | 
| Geometric Mean Concentration of Antibodies to Polyribosylribitol Phosphate (PRP) Antigen | Participant serum samples were collected for analysis by radioimmunoassay (RIA) to determine the geometric mean concentration of antibodies to polyribosylribitol phosphate (PRP), a Haemophilus influenzae type b (Hib) capsular polysaccharide. | Month 5 (one month after receiving Vaccination 3) | 
| Geometric Mean Concentration of Antibodies to Diphtheria Toxin | Participant serum samples were collected for analysis with a Micrometabolic Inhibition Test (MIT) to determine the geometric mean concentration of neutralizing antibodies to diphtheria toxin. The unit of measure is International Units/mL (IU/mL). | Month 5 (one month after receiving Vaccination 3) | 
| Geometric Mean Concentration of Antibodies to Tetanus Toxin | Participant serum samples were collected for analysis by Enzyme-linked Immunosorbent Assay (ELISA) to determine the geometric mean concentration of antibodies to tetanus toxin. The unit of measure is International Units/mL (IU/mL). | Month 5 (one month after receiving Vaccination 3) | 
| Geometric Mean Concentrations of Antibodies to Pertussis Antigens | Participant serum samples were collected for analysis by ELISA to determine the geometric mean concentration of antibodies (Abs) to the following Pertussis antigens: pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and fimbriae types (FIM) 2&3. The unit of measure is ELISA Units/mL (EU/mL). | Month 5 (one month after receiving Vaccination 3) | 
| Geometric Mean Titers for Antibodies to Inactivated Poliovirus 1-3 (IPV1-3) | Participant serum samples were collected for analysis with a Micrometabolic Inhibition Test (MIT) to determine the geometric mean titer of neutralizing antibodies (Abs) to Inactivated Poliovirus 1, 2, & 3 (IPV1, IPV2, & IPV3). The unit of measure is titer, expressed as the reciprocal dilution of the highest dilution that neutralizes 50% of the challenge virus. | Month 5 (one month after receiving Vaccination 3) | 
| Percentage of Participants Responding to Polyribosylribitol Phosphate (PRP) Antigen, Diptheria Toxin (D), Tetanus Toxin (T), and Inactivated Poliovirus 1, 2, & 3 (IPV1, IPV2, & IPV3) | Participants were considered as responding if the observed concentration or titer for antibodies (Abs) to specific antigens exceeded the following thresholds: For anti-PRP Abs (Hib capsular polysaccharide) - Response defined as a concentration ≥1 µg/mL (measured by RIA); For anti-D Abs - Response defined at 2 concentrations: ≥0.01 IU/mL and ≥0.10 IU/mL (measured by MIT); For anti-T Abs - Response defined at 2 concentrations: ≥0.01 IU/mL and ≥0.10 IU/mL (measured by ELISA); For anti-IPV1, anti-IPV2, and anti-IPV3 Abs - Response defined as a titer ≥ 8 (measured by MIT). The percentage of participants considered as responding to the individual antigen (per the response threshold[s]) were assessed. | Month 5 (one month after receiving Vaccination 3) | 
| Geometric Mean Titer of Anti-Meningococcal Group C Polysaccharide Conjugate (MCC) Antibodies | Participant serum samples were collected to determine the geometric mean titer of anti-MCC antibodies, measured by the Serum Bactericidal Antibody assay using rabbit complement (rSBA). The unit of measure is titer, expressed as the reciprocal of the final serum dilution giving ≥50% killing of the challenge bacterial strain. | Month 3 (one month after receiving Vaccination 2) | 
| Percentage of Participants With an Anti-Meningococcal Group C Polysaccharide Conjugate (MCC) Antibody Titer ≥8 | The percentage of participants with an anti-MCC antibody titer ≥8 was assessed. Participant serum samples were collected and analyzed for anti-MCC antibodies with the Serum Bactericidal Antibody assay using rabbit complement (rSBA). | Month 3 (one month after receiving Vaccination 2) | 
| Percentage of Participants With a Body Temperature ≥38°C After Each Vaccination | The percentage of participants with a body temperature ≥38.0°C from Day 1 to Day 5 after each vaccination was assessed. Per protocol, the participant's parent(s)/legal representative recorded daily body temperature measurements each evening by the axillary route (N=3 collected via rectal route; N=1 collected via oral route) and recorded these observations on the Vaccine Report Card (VRC). Temperatures were based on actual temperatures recorded with no adjustments for the route of assessment. | Up to Day 5 following each vaccination | 
| Number of Participants Experiencing a Solicited Injection Site Reaction (ISR) Related to the PR5I/Pediacel® Vaccination | The number of participants experiencing solicited ISRs related to the PRI5 or Pediacel® vaccination was assessed. Solicited ISRs (erythema, pain and swelling) occurring at the PR5I or Pediacel® injection site were always considered related to the PR5I or Pediacel® vaccine, respectively. All AEs/ISRs were recorded on the VRC by the participant's parent(s)/legal representative. Data are presented for the number of participants experiencing solicited ISRs up to Day 5 after each vaccination and after any vaccination. | Up to Day 5 following each vaccination | 
| Number of Participants Experiencing a Solicited Injection Site Reaction (ISR) Related to the NeisVac-C® (MCC) Vaccination | The number of participants experiencing solicited ISRs related to the NeisVac-C® (MCC) vaccination was assessed. Solicited ISRs (erythema, pain and swelling) occurring at the NeisVac-C® (MCC) injection site were always considered related to the NeisVac-C® (MCC) vaccine. All AEs/ISRs were recorded on the VRC by the participant's parent(s)/legal representative. Data are presented for the number of participants experiencing solicited ISRs up to Day 5 after each NeisVac-C® vaccination and after any NeisVac-C® vaccination. | Up to Day 5 following each vaccination | 
| Number of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) Related to the PR5I/Pediacel® Vaccination | The number of participants experiencing unsolicited ISRs related to the PRI5 or Pediacel® vaccination was assessed. Unsolicited ISRs occurring at the PR5I or Pediacel® injection site were always considered related to the PR5I or Pediacel® vaccine, respectively. All AEs/ISRs were recorded on the VRC by the participant's parent(s)/legal representative. Data are presented for the number of participants experiencing unsolicited ISRs up to Day 15 after each vaccination and after any vaccination. | Up to Day 15 following each vaccination | 
| Number of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) Related to the NeisVac-C® (MCC) Vaccination | The number of participants experiencing unsolicited ISRs related to the NeisVac-C® (MCC) vaccination was assessed. Unsolicited ISRs occurring at the NeisVac-C® (MCC) injection site were always considered related to the NeisVac-C® (MCC) vaccine. All AEs/ISRs were recorded on the VRC by the participant's parent(s)/legal representative. Data are presented for the number of participants experiencing unsolicited ISRs up to Day 15 after each NeisVac-C® vaccination and after any NeisVac-C® vaccination. | Up to Day 15 following each vaccination | 
| Number of Participants Experiencing a Solicited Systemic Adverse Event (AE) | The number of participants experiencing solicited systemic AEs (crying, decreased appetite, irritability, somnolence, pyrexia, and vomiting) was assessed. Each day from Day 1 to Day 5 following each vaccination, the participant's parent(s)/legal representative recorded all solicited AEs on the VRC. Data are presented for the number of participants experiencing solicited AEs up to Day 5 after each vaccination and after any vaccination. | Up to Day 5 following each vaccination | 
| Number of Participants Experiencing an Unsolicited Systemic Adverse Event (AE) | The number of participants experiencing unsolicited systemic AEs was assessed. Data are presented for the number of participants experiencing unsolicited AEs up to Day 15 after each vaccination and after any vaccination. | Up to Day 15 following each vaccination | 
| Number of Participants Experiencing a Serious Adverse Event (SAE) | An SAE is an adverse event (AE) that: results in death; is life threatening; results in persistent or significant disability or incapacity; results in or prolongs a hospitalization; is a congenital anomaly or birth defect; is a cancer; or may jeopardize the participant, potentially require medical or surgical intervention. | Up to  6 months (at any time during the study) |