A Clinical Trial to Study the Safety, Tolerance and Immunogenic Response to MCV4, Tdap and Bivalent rLP2086 Vaccine When Given at the Same Time to Children Between the Ages of 10 Through 12 Years of Age

Study Overview
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Brief Summary
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This is a clinical study to assess the safety, tolerance and immunogenic response to MCV4(quadrivalent meningococcal polysaccharide conjugate, meningococcal serogroups A,C,Y, and W135), Tdap (diphtheria, tetanus, and acellular pertussis), and bivalent rLP2086 vaccine. Healthy male and female subjects, between the ages of 10 to 12 years old, will be randomized into 1 of 3 groups. The subjects, investigators, site staff and sponsor will be blinded to all injections given throughout the study. An unblinded administrator will be responsible to administer the vaccinations to all subjects and will be unblinded to the subject randomization in order to determine which subjects were in randomized to group 3 so they may receive their catch-up vaccinations of MCV4 and Tdap. A final telephone contact will be conducted with all subjects 6-months post their last vaccination to obtain safety information.

Official Title
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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

Conditions
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Vaccines, Meningococcal Vaccines

Intervention / Treatment
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* Biological: rLP2086 + MCV4 + Tdap
* Biological: MCV4 + Tdap + saline
* Biological: rLP2086 + saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Parent /legally authorized representative and subjects who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures. Male or female subject aged greater than or equal to 10 and <13 years at the time of enrollment. Available for the entire study period and can be reached by telephone. Healthy subject as determined by medical history, physical examination, and judgment of the investigator. 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. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study. Exclusion Criteria: Previous vaccination with any meningococcal serogroup B vaccine. Vaccination with any diphtheria, tetanus or pertussis vaccine within 5 years of the first study vaccination. Previous vaccination with any MCV4 vaccine. A previous anaphylactic reaction to any vaccine or vaccine-related component. Contraindication to vaccination with MCV4 and/or Tdap vaccine. Subjects receiving any allergen immunotherapy with a non-licensed product or receiving allergen immunotherapy with a licensed product and are not on stable maintenance doses. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection. A known or suspected defect of the immune system that would prevent an immune response to the vaccine, such as subjects with congenital or acquired defects in B cell function, those receiving chronic systemic (oral, intravenous or intramuscular) corticosteroid therapy, or those receiving immunosuppressive therapy. Subjects with terminal complement deficiency may not be included. History of culture-proven disease caused by Neisseria meningitidis or Neisseria gonorrhoea. Significant neurological disorder or history of seizure (excluding simple febrile seizure). Receipt of any blood products, including immunoglobulin within 6 months before the first study vaccination. Current chronic use of systemic antibiotics. Any neuroinflammatory or autoimmune condition, including, but not limited to, transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 12 Years

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MCV4 + Tdap+ rLP2086<br>Group 1 - MCV4 + Tdap + rLP2086 | Biological: rLP2086 + MCV4 + Tdap<br>* At visit 1, group 1 will receive MCV4 + Tdap vaccines concomitantly with an injection of rLP2086. At visits 3 and 5 (Months 2 and 6), group 1 will receive an injection of rLP2086.<br>|
| Active Comparator: MCV4 + Tdap + saline<br>Group 2, MCV4 + Tdap+ saline | Biological: MCV4 + Tdap + saline<br>* At visit 1, group 2 will receive MCV4 + Tdap vaccines concomitantly with an injection of saline. At visits 3 and 5 (months 2 and 6), this group will receive a saline injection only.<br>|
| Placebo Comparator: Saline + saline + rLP2086<br>Group 3- rLP2086 + saline | Biological: rLP2086 + saline<br>* At visit 1, group 3 will receive 2 injections of saline concomitantly with an injection of rLP2086. At visits 3 and 5 (Months 2 and 6), group 3 will receive an injection of rLP2086. Subjects randomized to this group will receive MCV4 and Tdap following their final visit blood draw (Visit 6).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentrations (GMC) for Diphtheria and Tetanus Antigens | Antibody GMCs of 2 antigens of diphtheria and tetanus toxoid were computed in International Units per milliliter (IU/mL) along with corresponding 2-sided 95 percent (%) confidence intervals (CIs). Here, 'number of participants analyzed' signifies participants with valid and determinate assay results for given antigen. | 1 Month after Vaccination 1 | 
| Geometric Mean Concentrations (GMC) for Acellular Pertussis Antigens | Antibody GMCs of 4 acellular pertussis antigens (pertussis toxoid, pertussis filamentous hemagglutinin, pertussis pertactin and pertussis fimbrial agglutinogens types 2+3) were computed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL) along with corresponding 2-sided 95% CIs. | 1 Month after Vaccination 1 | 
| Geometric Mean Titer (GMT) for Meningococcal Conjugate Vaccine (MCV4) Antigens | Antibody GMTs of 4 MCV4 antigens (serogroup A, serogroup C, serogroup Y and serogroup W-135) were computed along with corresponding 2-sided 95% CIs. | 1 Month after Vaccination 1 | 
| Serum Bactericidal Assay Using Human Complement (hSBA) GMTs of PMB80 [A22] and PMB2948 [B24] 1 Month After Vaccination 3 | Antibody hSBA GMTs of primary strain PMB80 [A22] and PMB2948 [B24] were computed along with corresponding 2-sided 95% CIs. hSBA titers from the 2 primary strains were logarithmically transformed for analysis. Here, 'number of participants analyzed' signifies evaluable immunogenicity population and 'N' signifies participants with valid and determinate assay results for given strain for each group, respectively. | 1 Month after Vaccination 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroresponse for Tetanus, Diphtheria and Acellular Pertussis (Tdap) and Meningococcal Conjugate Vaccine (MCV4) Antigens | Seroconversion rate for Tdap antigens was defined as greater than or equal to (>=) 4-, 2-fold rise in antibody concentration, if prevaccination antibody concentration was less than or equal to (<=), greater than (>) cutoff value, respectively. For MCV4 antigens >=4-fold rise on serum bactericidal assay using rabbit complement (rSBA) titers if baseline value >= lower limit of quantitation (LLOQ), postdose rSBA titers >=2×LLOQ if baseline value was less than (<) LLOQ. Cutoff value =0.1 IU/mL for diphtheria and tetanus, 0.9,2.9,3.0,10.6 EU/mL for pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae agglutinogens types 2 + 3, respectively. | 1 Month after Vaccination 1 | 
| Percentage of Participants Achieving Predefined Antibody Level for Diphtheria and Tetanus Antigens | Participants with antibody concentration level of greater than or equal to 1.0 IU/mL for diphtheria and tetanus antigens were computed along with corresponding 2-sided 95% CIs. | 1 Month after Vaccination 1 | 
| Serum Bactericidal Assay Using Human Complement (hSBA) GMTs of PMB80 [A22] and PMB2948 [B24] Before Vaccination 1 and 1 Month After Vaccination 2 | Antibody hSBA of primary strain PMB80 [A22] and PMB2948 [B24] were computed along with corresponding 2-sided 95% CIs. hSBA titers from the 2 primary strains were logarithmically transformed for analysis. | Before Vaccination 1, 1 Month after Vaccination (Vac) 2 | 
| Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titer >= Lower Limit of Quantitation (LLOQ) | Percentage of participants achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95% CIs. LLOQ was 1:16 for PMB80 [A22] and 1:8 for PMB2948 [B24]. | Before Vaccination 1, 1 Month after Vaccination (Vac) 2, 3 | 
| Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titer >= Prespecified Titer Level | Antibody hSBA of primary strain PMB80 [A22] and PMB2948 [B24] with hSBA titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64, and >=1:128 were computed along with corresponding 2-sided 95% CIs. | Before Vaccination 1, 1 Month after Vaccination (Vac) 2, 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, rLP2086, MCV4, Tdap, meningitis B, N. meningitidis serogroup B, adolescents, observer-blind