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

Phase 3

Completed

Conditions: Bacterial Infections
Virus Diseases
Neisseria Meningitidis

Interventions: Biological: PR5I
Biological: Pediacel®
Biological: NeisVac-C®
Biological: RotaTeq®
Biological: Prevenar 13®

Registration Number: NCT01839188

Lead Sponsor: MCM Vaccines B.V.

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 385

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PR5I (V1); Pediacel® (V2); PR5I (V3)	PR5I	\[Vaccination 1\]: 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.
PR5I (V1); Pediacel® (V2); PR5I (V3)	Prevenar 13®	\[Vaccination 1\]: 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.
PR5I (V1); Pediacel® (V2); PR5I (V3)	Pediacel®	\[Vaccination 1\]: 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.
PR5I (V1); Pediacel® (V2); PR5I (V3)	NeisVac-C®	\[Vaccination 1\]: 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.
PR5I (V1); Pediacel® (V2); PR5I (V3)	RotaTeq®	\[Vaccination 1\]: 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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With an Anti-Hepatitis B Surface Antigen (HBsAg) Antibody Titer ≥10 mIU/mL	Month 5 (one month after receiving Vaccination 3)	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.
Percentage of Participants With an Anti-Polyribosylribitol Phosphate (PRP) Antibody Titer ≥0.15 µg/mL	Month 5 (one month after receiving Vaccination 3)	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Experiencing a Solicited Injection Site Reaction (ISR) Related to the PR5I/Pediacel® Vaccination	Up to Day 5 following each 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.
Number of Participants Experiencing a Solicited Injection Site Reaction (ISR) Related to the NeisVac-C® (MCC) Vaccination	Up to Day 5 following each 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.
Number of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) Related to the PR5I/Pediacel® Vaccination	Up to Day 15 following each 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.
Number of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) Related to the NeisVac-C® (MCC) Vaccination	Up to Day 15 following each 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.
Number of Participants Experiencing a Solicited Systemic Adverse Event (AE)	Up to Day 5 following each vaccination	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.
Number of Participants Experiencing an Unsolicited Systemic Adverse Event (AE)	Up to Day 15 following each vaccination	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.
Number of Participants Experiencing a Serious Adverse Event (SAE)	Up to ~6 months (at any time during the study)	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.
Percentage of Participants Responding to Polyribosylribitol Phosphate (PRP) Antigen, Diptheria Toxin (D), Tetanus Toxin (T), and Inactivated Poliovirus 1, 2, & 3 (IPV1, IPV2, & IPV3)	Month 5 (one month after receiving Vaccination 3)	Participants were considered as responding if the observed concentration or titer for antibodies (Abs) to specific antigens exceeded the following thresholds: 1. For anti-PRP Abs (Hib capsular polysaccharide) - Response defined as a concentration ≥1 µg/mL (measured by RIA); 2. For anti-D Abs - Response defined at 2 concentrations: ≥0.01 IU/mL and ≥0.10 IU/mL (measured by MIT); 3. For anti-T Abs - Response defined at 2 concentrations: ≥0.01 IU/mL and ≥0.10 IU/mL (measured by ELISA); 4. 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.
Geometric Mean Titer of Anti-Meningococcal Group C Polysaccharide Conjugate (MCC) Antibodies	Month 3 (one month after receiving Vaccination 2)	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.
Percentage of Participants With an Anti-Meningococcal Group C Polysaccharide Conjugate (MCC) Antibody Titer ≥8	Month 3 (one month after receiving Vaccination 2)	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).
Percentage of Participants With a Body Temperature ≥38°C After Each Vaccination	Up to Day 5 following 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.
Geometric Mean Concentration of Antibodies to Hepatitis B Surface Antigen (HBsAg)	Month 5 (one month after receiving Vaccination 3)	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).
Geometric Mean Concentration of Antibodies to Polyribosylribitol Phosphate (PRP) Antigen	Month 5 (one month after receiving Vaccination 3)	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.
Geometric Mean Concentration of Antibodies to Diphtheria Toxin	Month 5 (one month after receiving Vaccination 3)	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).
Geometric Mean Concentration of Antibodies to Tetanus Toxin	Month 5 (one month after receiving Vaccination 3)	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).
Geometric Mean Concentrations of Antibodies to Pertussis Antigens	Month 5 (one month after receiving Vaccination 3)	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).
Geometric Mean Titers for Antibodies to Inactivated Poliovirus 1-3 (IPV1-3)	Month 5 (one month after receiving Vaccination 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.