A Phase 2, Randomized, Active-controlled, observer-blindED Trial, to Assess the Safety, Tolerability, and Immunogenicity of MCV4, TDAP Vaccine and bivalent RLP2086 Vaccine When Administered Concomitantly in Healthy Subjects Aged ≥10 to <13 Years

INTERVENTION: Product Name: Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein Product Code: PF‐05212366 Pharmaceutical Form: Suspension for injection Pharmaceutical form of the placebo: Suspension for injection Route of administration of the placebo: Intramuscular use CONDITION: Prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MnB) in adolescents and young adults, aged 10 through 25 years. ; MedDRA version: 14.1 Level: LLT Classification code 10004049 Term: Bacterial meningitis System Organ Class: 100000004862 Therapeutic area: Body processes [G] ‐ Immune system processes [G12] PRIMARY OUTCOME: Main Objective: demonstrate immune response(based on geometric mean titer GMT)induced by MCV4 and Tdap vaccines given with bivalent rLP2086 vaccine(Group1)is noninferior to immune response induced by MCV4 and Tdap vaccines alone(Group2)when measured 1month after first vaccination(Visit2)in both groups. Immune response to all components of MCV4 and Tdap vaccines will be assessed.; demonstrate immune response (based on GMT)induced by bivalent rLP2086 vaccine,as measured by serum bactericidal assay using human complement(hSBA)performed with 2MnB strains, 1expressing LP2086 subfamily A and 1expressing LP2086 subfamily B proteins,given with MCV4 and Tdap vaccines(Group1)is noninferior to the immune response induced by bivalent rLP2086 vaccine alone(Group3),when measured 1month after the third vaccination(Visit6)with bivalent rLP2086 vaccine in both groups; evaluate safety profile of bivalent rLP2086 vaccine as measured by proportion of subjects reporting local reactions,systemic events,adverse events Primary end point(s): The primary endpoints for the co‐primary objectives are:; The primary endpoints for the first co‐primary objective are the geometric mean titers (GMTs) or geometric mean concentrations (GMCs) for each of the antibodies reactive with each of the 10 antigenic components in the marketed vaccines at visit 2, among subjects in Groups 1 and 2; The primary endpoints for the second co‐primary objective are the hSBA GMTs for each of the 2 primary strains (PMB80 [A22] and PMB2948 [B24]) at visit 6, among subjects in Groups 1 and 3.; ; Primary Endpoints : GMs; Marketed Vaccine Components ; Meningococcal serogroup A : GMT; Meningococcal serogroup C : GMT; Meningococcal serogroup Y : GMT; Meningococcal serogroup W‐135 : GMT; Diphtheria : GMC; Tetanus : GMC; Pertussis toxoid (PT) : GMC; Pertussis filamentous hemagglutinin (FHA) : GMC; Pertussis pertactin (PRN) : GMC; Pertussis fimbriae types 2 and 3 (FIM) : GMC; rLP2086 Vaccine Strains ; PMB80 (A22) : GMT; PMB2948 (B24) : GMT; ; All of the safety endpoints will be applied to each group.; • Proportion of subjects reporting local reactions (pain, redness and swelling) and by severity after each vaccination visit.; • Proportion of subjects reporting systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, muscle pain other than muscle pain at any injection site, and joint pain) and by severity after each vaccination visit.; • Proportion of subjects reporting the use of antipyretic medication after each vaccination visit.; • Proportion of subjects who develop at least one adverse event occurring during the following time periods:; • 30 days after each vaccination; • 30 days after any vaccination; • During the vaccination phase [from the first study vaccination (Visit 1) through 1 month after the last study vaccination (Visit 6)]; • Proportion of subjects with at least one SAE during the following time periods:; • 30 days after each vaccination; • 30 days after any vaccination; • During the vaccination phase [from the first study vaccination (Visit 1) through 1 month after the last study vaccination (Visit 6)]; • During the follow‐up phase [from 1 month after the last study vaccination (Visit 6) through 6 months after the third study vaccination (Visit 7)]; • Throughout the study period [from the first study vaccination (Visit 1) through 6 months after the third study vaccination (Visit 7)]. ; • Proportion of subjects reporting at least one immediate adverse event after each vaccination.; • Proportion of subjects reporting at least one newly diagnosed major illness, during the follow‐up phase [from 1 month after the last study vaccination (Visit 6) through 6 months after the third study vaccination (Visit 7)].; Secondary Objective: To describe the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 2 MnB strains, one expressing LP2086 subfamily A and one expressing LP2086 subfamily B proteins, measured 1 month after the third vaccination (Visit 6) with bivalent rLP2086 vaccine (Group 3).; ; To describe the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 2 MnB strains, one expressing LP2086 subfamily A and one expressing LP2086 subfamily B proteins, measured 1 month after the second vaccination (Visit 4) with bivalent rLP2086 vaccine (Group 3); ; To describe the seroresponses to antigens contained in MCV4 and Tdap (Groups 1 and 2) when measured 1 month after vaccination with MCV4 and Tdap (Visit 2); Timepoint(s) of evaluation of this end point: • One month post vaccination 1 and last vaccination for first and secondary co‐primary immunogenicity endpoint ; ; Safety Endpoints; Local Reactions, Systemic Events, Antipyretic Use; • 7days after each vaccination; ; AE’s; • 30 days after each/any vaccination; • During vaccination [from first through 1 month after last study vaccination ]; SAE’s; • 30 days after each/any vaccination; • During vaccination [from first through 1 month after last study vaccination ]; • During the follow‐up [from 1 month after last through 6 months after third study vaccination ]; • Throughout study [from first through 6 months after third study vaccination ; Immediate AE’s; • 30min after each vaccination; Newly Diagnosed Major Illness; • 1 month after last through 6 months after third study vaccination SECONDARY OUTCOME: Secondary end point(s): • The seroresponse rate at visit 2 for each of the 10 marketed vaccine antigens in Group 1 and Group 2. ; • For Tdap vaccine, the booster response is used, which is defined as at least 4‐fold rise in antibody concentration if the pre‐vaccination concentration is = cutoff value and at least 2‐fold rise in antibody concentration if the pre‐vaccination concentration is > cutoff value. The cutoff values are described as below: ; ; Table 1. Cutoff for Booster Response ; ; Antigens : Cutoff ; Tdap ; Diphtheria : 0.1 IU/mL ; Tetanus : 0.1 IU/mL ; Pertussis toxoid (PT) : 0.9 EU/mL ; Pertussis filamentous hemagglutinin (FHA) : 2.9 EU/mL ; Pertussis pertactin (PRN) : 3.0 EU/mL ; Pertussis fimbriae types 2 and 3 (FIM) : 10.6 EU/mL ; ; • For MCV4, the seroconversion rate is used, which is defined as =4‐fold rise on serum bactericidal assay using rabbit complement (rSBA) titers ; • Proportion of subjects (Groups 1 and 2) who achieve an antibody level =1.0 IU/mL to tetanus and proportion of subjects (Groups 1 and 2) who achieve an antibody level =1.0 IU/mL to diphtheria toxoid ; • hSBA titers as measured by GMTs for each of the 2 primary MnB test strains (PMB80 [A22] and PMB2948 [B24]) at each applicable blood sampling time point ; • Proportion of subjects with hSBA titers =LLOQ, =1:4, =1:8, =1:16 , =1:32, =1:64, =1:128 at each blood draw visit, for each of the 2 primary strains (PMB80 [A22] and PMB2948 [B24]) ; Timepoint(s) of evaluation of this end point: • One month after vaccination 1. ; • One month after vaccination 1. ; • One month after vaccination 1. ; • One month after first, second, and third vaccination. ; • One month after first, second, and third vaccination ; INCLUSION CRITERIA: 1. Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject (and a legally authorized representative) has been informed of all pertinent aspects of the study. 2. Parent /legally authorized representative and subjects who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures. 3. Male or female subject aged =10 and <13 years at the time of enrollment. 4. Available for the entire study period and can be reached by telephone. 5. Healthy subject as determined by medical history, physical examination, and judgment of the investigator. 7. Male and female subjects of childbearing potential must agree to use a highly effective 6. Has received full series (5‐dose series is preferred, 4‐dose catch up series is allowed) of diphtheria, tetanus and pertussis (whole cell or acellular) vaccines per country specific recommendations applicable at the time of receipt.