Clinical Study of Meningococcal ACYWX Conjugate Vaccine, in 12-16 Month Olds

Study Overview
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Brief Summary
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Out of the 13 identified serogroups of Neisseria meningitidis (Nm) the six serogroups (A, B, C, W, Y and X) are responsible for majority of infections. Presently available vaccines effectively protect against A, B, C, W and Y serogroups; but no vaccine that is protective against serogroup X is available yet. Serum Institute of India Private Limited (SIIPL) has developed a conjugate vaccine against serogroups A, C, Y, W and X (NmCV-5). The first-in-human Phase 1 study was among 60 healthy adults in USA did not show no any safety issues. This phase 2 study is designed to evaluate safety and immunogenicity of the non-adjuvanted and adjuvanted formulations of NmCV-5 in healthy children 12-16 months of age, in comparison with the licensed quadrivalent meningococcal conjugate vaccine (Menactra®). Both vaccines will be administered in two dose schedule 3 months apart. among vaccine-naïve healthy subjects in Mali. Safety will be assessed by collecting solicited reactions till day 7 post each dose whereas adverse events will be collected throughout the study. Each subject will be followed up for 84 days post each vaccine dose. The vaccine immunogenicity will measured using a rabbit complement serum bactericidal activity assay (rSBA).

Official Title
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A Phase 2, Observer-blind, Randomized, Controlled Study to Evaluate the Safety and Immunogenicity of Two Formulations of Investigational Meningococcal Groups ACYWX Conjugate Vaccine, Administered to Healthy Malian Children 12-16 Months of Age

Conditions
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Meningitis, Meningococcal

Intervention / Treatment
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* Biological: Non-adjuvanted study formulation NmCV-5
* Biological: Adjuvanted study formulation NmCV-5
* Biological: Menactra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female children between 12 months and 16 months old inclusive (minimum 365 days of age and maximum 16 months plus 29 days of age); For whom parent(s)/legal guardian(s) have given written informed consent after the nature of the study has been explained according to local regulatory requirements; Who the investigator believes that their parent(s)/ guardian(s) will be available for all the subject visits and would comply with the requirements of the protocol (e.g., timely reporting of adverse events, availability for study site visits and home visits); Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Individuals who completed their local infant EPI schedule through 9 months of age (except MenAfriVac dose). A birth dose of OPV is not required) Exclusion Criteria: History of any meningococcal vaccine administration. Current or previous, confirmed or suspected disease caused by N. meningitidis. Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrolment. History of severe allergic reactions after previous vaccinations or hypersensitivity to any study vaccine component including tetanus, diphtheria and diphtheria toxoid (CRM197). Acute or chronic, clinically significant pulmonary, cardiovascular, metabolic, neurological, hepatic, or renal functional abnormality, as determined by medical history or physical examination. Any confirmed or suspected condition with impaired/altered function of immune system (immunodeficient or autoimmune conditions). Have any bleeding disorder which is considered as a contraindication to intramuscular injection or blood draw. Severe acute malnutrition. A family history of congenital or hereditary immunodeficiency. History of either hepatitis B or hepatitis C virus infection or human immunodeficiency virus infection. Major congenital defects. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the study vaccination or planned use throughout the study period. (For corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg per day. Inhaled, intranasal and topical steroids are allowed). Administration of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months or planned use throughout the study period. Administration of any vaccine within 28 days prior to enrolment in the study or planned administration of any vaccine within 14 days before or after any study vaccination. Use of any investigational or non-registered drug or vaccine within 30 days prior to the administration of study vaccines or planned during the study. Malaria infection as confirmed by a Rapid Diagnostic Test. Individuals who are close family members of individuals conducting this study. Have experienced a moderate or severe acute infection and/or fever (defined as temperature ≥ 37.5°C) within 3 days prior to enrolment. Have received systemic antibiotic treatment within 3 days prior to enrolment. Non-residence in the study area or intent to move out within six months. Any condition which, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 16 Months

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
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjuvanted study formulation NmCV-5<br>Subjects in this arm will receive adjuvanted formulation of polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days. | Biological: Adjuvanted study formulation NmCV-5<br>* Adjuvanted formulation of polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysacchride antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to CRM protein. The diluent contains Alum as adjuvant with Normal Saline. Each antigen content is 5 micrograms per 0.5 mL dose of vaccine<br>* Other names: Adj MenACYWX;|
| Experimental: Non-adjuvanted study formulation NmCV-5<br>Subjects in this arm will receive non-adjuvanted formulation of polyvalent conjugated vaccine against meningococcal serogroups A,C,Y,W & X. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days. | Biological: Non-adjuvanted study formulation NmCV-5<br>* Non-adjuvanted formulation of polyvalent conjugate meningococcal vaccine against serogroups A,C,Y,W&X (NmCV-5) is available as lyophilised powder of polysacchride antigens A&X conjugated to tetanus toxoid and C,Y&W conjugated to CRM protein. The diluent contains 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. Dose to be administered is 0.5 mL intramuscularly in a two dose series separated by atleast 84 days. | Biological: Menactra<br>* Menactra is available as ready to used solution containing polysacchride 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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Solicited Adverse Event | Percentage of subjects with at least one severe solicited AE within 7 days after any study vaccination (Days 0-6 and Days 84-90) | 7 days post each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotective rSBA Titres | Percentage of subjects with rSBA titer ≥ 8 against serogroups A, C, W, Y and X at Visits Day 0 (Baseline), Day 28 (28 days after dose 1), Day 84 (prior to dose 2) and Day 112 (28 days after dose 2) | 112 days | 
| Long Term Protective rSBA Titres | Percentage of subjects with rSBA titer ≥ 128 against serogroups A, C, W, Y and X at Visits Day 0, Day 28, Day 84 and Day 112 | 112 days | 
| Rise in rSBA Titres | Percentage of subjects with fourfold rise in rSBA titers against serogroups A, C, W, Y and X at Visits Day 28 and Day 112. For subjects with a pre-vaccination rSBA titer < 8, a post-vaccination titer of ≥ 32; For subjects with a pre-vaccination rSBA titer ≥ 8, an increase in rSBA titer of at least 4 times the pre-vaccination titer | 112 days | 
| Geometric Mean of rSBA Titres | rSBA GMT for serogroups A, C, W, Y and X at Visits Day 0, Day 28, Day 84 and Day 112 | 112 Days | 
| Solicited Reactions | Solicited local and systemic AEs reported during the 7 days after each vaccination (Days 0-6 and Days 84-90); | 7 days post each vaccination | 
| Adverse Events | Unsolicited AEs reported during 28 days after each vaccination (Days 0-27 and Days 84-111); | 112 Days | 
| Other Adverse Events | AEs leading to premature withdrawal during the entire study period; | 168 Days | 
| Serious Adverse Events | SAEs reported during the entire study period | 168 Days | 

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