Study to Assess Immunegnicity & Safety of Pentavalent Meningococcal Vaccine (NmCV-5)

Study Overview
=================
Brief Summary
-----------------
This observer-blind, randomized, active controlled trial will be conducted among 2-29 year olds in two sites (Mali and The Gambia). The objectives of the study are to assess and compare the immunogenicity and safety of NmCV-5 with that of Menactra. A total of 1800 eligible participants (who or their parents/guardians have given written informed consent) will be randomised 2:1 (NmCV-5: Menactra) in each of the three age strata 18-29 years, 11-17 years & 2-10 years (400 NmCV-5 recipients & 200 Menactra recipients in each age strata). Each subject will receive a single dose of study vaccine and will be followed up for 6 months post vaccination during which solicited reactions (for seven days), unsolicited AEs (28 days) and SAEs (until the end of study i.e. 168 days after vaccination) will be collected. A blood sample will be collected at baseline (pre-vaccination) and at day 28 post-vaccination for immunogenicity assessment by a Serum Bactericidal Activity assay using rabbit complement (rSBA).

Official Title
-----------------
Phase 3, Observer-blind, Randomized, Active Controlled Trial to Assess the Safety of an Investigational Meningococcal Serogroups ACYWX Conjugate Vaccine (NmCV-5) and Compare Its Immunogenicity to a Licensed Meningococcal Serogroups ACYW Conjugate Vaccine (Menactra®), in Healthy Subjects 2 to 29 Years of Age

Conditions
-----------------
Meningococcal Meningitis

Intervention / Treatment
-----------------
* Biological: NmCV-5
* Biological: Menactra


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or non-pregnant female 2 through 29 years of age, inclusive, at the time of study IP administration. Written informed consent obtained from subjects at least 18 years of age or from their parent/guardian for subjects less than 18 years of age with additional subject assent obtained as appropriate for participating community (i.e. subjects at least 13 years of age in Mali or at least 12 years of age in The Gambia). Subject or parent/guardian with subject reside in study site area and are able and willing to adhere to all protocol visits and procedures. Female subjects of childbearing potential must have practiced adequate contraception for 28 days prior to study IP administration and agree to continue adequate contraception until completion of their Day 29 visit. Female subjects of childbearing potential must have a negative pregnancy test within 24 hours prior to study IP administration Exclusion Criteria: Acute illness, at the time of study IP administration (once acute illness is resolved, if appropriate, as per investigator assessment, subject may be re-revaluated for eligibility). Recorded fever (for eligibility purpose defined as a body temperature greater than 37.5°C) within 3 days prior to study IP administration (once fever/acute illness is resolved, if appropriate, as per investigator assessment, subject may be re-revaluated for eligibility). Previous immunization with a Neisseria meningitidis vaccine other than MenAfriVac® during the previous five years. Current or previous, confirmed disease caused by Neisseria meningitidis. Household contact with or intimate exposure to an individual with any laboratory confirmed Neisseria meningitidis infection within 90 days prior to study IP administration. Known hypersensitivity to any component of the study IPs (i.e., NmCV-5 or Menactra®). History of significant hypersensitivity reactions to any previous vaccine. Administration of any vaccine other than study IPs within 28 days prior to study IP administration or planned administration prior to completion of the study Day 29 visit. Administration of any investigational drug within 30 days prior to study IP administration or planned administration during the study period. Unwilling to avoid (or their child to avoid, if the subject) the ingestion of herbal or other traditional medications during the study period. Administration of immunoglobulin or any blood product within 90 days prior to study IP administration or planned administration during the study period. Administration of immunosuppressants or other immune modifying agents within 90 days prior to study IP administration Administration of systemic antibiotic treatment within 3 days prior to study IP administration. Any history of or evidence for chronic clinically significant (as per investigator assessment) disorder or disease (including, but not limited to, immunodeficiency, autoimmunity, malnutrition, congenital abnormality, bleeding disorder, and pulmonary, cardiovascular, metabolic, neurologic, renal, or hepatic disease). Any history of human immunodeficiency virus, chronic hepatitis B or chronic hepatitis C infections. History of meningitis, seizures, Guillain-Barré syndrome (GBS), or other neurological disorders. History of or family history of congenital or hereditary immunodeficiency. Any condition that in the opinion of the investigator might compromise the safety or well-being of the subject or compromise adherence to protocol procedures or interfere with planned safety and immunogenicity assessments. Pregnancy Previous inclusion in the study of five immediate family members (i.e., biological father, mother, subject, and brothers and sisters may be included up to a maximum of five members from the same immediate family).

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 29 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NmCV-5<br>Subjects in this arm will receive polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. A single dose of 0.5 mL will be administered intramuscularly. | Biological: NmCV-5<br>* Polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysaccharide antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to C reactive material (CRM) protein. The diluent is Normal Saline. Each antigen content is 5 micrograms per 0.5 mL dose of vaccine.<br>* Other names: MenACYWX;|
| Active Comparator: Menactra<br>Subjects in this arm will licensed quadrivalent conjugated vaccine against meningococcal serogroups A,C,Y, & W viz. Menactra. A single dose of 0.5 mL will be administered intramuscularly. | Biological: Menactra<br>* Menactra is available as ready to use solution containing polysaccharide antigens A,C,Y&WX conjugated to diphtheria toxoid. Each antigen content is 4 micrograms per 0.5 mL dose of vaccine<br>* Other names: MenACYW-D;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroresponse | Percentage of subjects with seroresponse, measured by rabbit complement serum bactericidal activity (rSBA) against serogroups A, C, Y, W and X. [Seroresponse is defined as a post-immunization (Day 29) rSBA titer of 32 or greater if the subject's pre-immunization (Day 1) rSBA titer was < 8; or a ≥ four-fold increase over baseline at Day 29 post-immunization if the subject's pre-immunization (Day 1) rSBA titer was ≥ 8]. | 28 Days post vaccination | 
| Geometric mean titres | Geometric mean titers (GMTs) measured by rSBA against serogroups A, C, Y, W and X on Day 29 | 28 Days post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited adverse events | Solicited AEs for 7 days following vaccination | 7 days post vaccination | 
| Unsolicited adverse events | Unsolicited AEs for 28 days following vaccination | 28 days post vaccination | 
| Serious adverse events (SAEs) | SAEs for 6 months following vaccination | 6 months post vaccination | 
| Seroprotective rSBA titres | Percentage of subjects with rSBA titer of ≥ 8 against serogroups A, C, Y, W, and X at Day 1 and Day 29 | 28 days post vaccination | 
| Long term protective rSBA titres | Percentage of subjects with rSBA titer of ≥ 128 against serogroups A, C, Y, W, and X at Day 1 and Day 29 | 28 days post vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neisseria meningitidis, conjugate meningococcal vaccine, Meningococcal serogroup X