Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Adults, Adolescents, Children, and Toddlers in India and Healthy Adolescents and Children in the Republic of South Africa

Study Overview
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Brief Summary
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This will be a Phase III, modified double-blind (open-label for toddlers in India), randomized, parallel-group, active-controlled, step-wise, multi-center study to compare and describe the immunogenicity and safety of MenACYW conjugate vaccine when administered as a single dose in healthy adults, adolescents, children, and toddlers in India and a modified double-blind, randomized, parallel-group, active-controlled, multi-center study to compare and describe the immunogenicity and safety of MenACYW conjugate vaccine when administered as a single dose in healthy adolescents and children in RSA.

Detailed Description
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Study duration per participant is approximately 31 to 45 days

Official Title
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Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Adults, Adolescents, Children, and Toddlers in India and Healthy Adolescents and Children in the Republic of South Africa

Conditions
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Healthy Volunteers (Meningococcal Infection)

Intervention / Treatment
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* Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine
* Biological: Meningococcal polysaccharide (serogroups A,C,Y and W-135) diphtheria toxoid conjugate vaccine
* Biological: Meningococcal polysaccharide (serogroups A, C, Y and W-135) vaccine
* Biological: Hepatitis A vaccine
* Biological: Measles, Mumps, and Rubella Virus Vaccine (MMR)
* Biological: Pneumococcal 13-valent conjugate vaccine
* Biological: DTwP-HepB-Hib-IPV vaccine
* Biological: Varicella vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Age in the defined range on the day of inclusion: For Adults: Aged ≥ 18 years on the day of inclusion For Children and Adolescents: Aged 2 to 17 years on the day of inclusion For Toddlers: Aged 12 to 23 months† on the day of inclusion - Z-score of ≥ -2 standard deviations (SD) on the Weight-for-height table of the World Health Organization (WHO) Child Growth Standards: For toddlers and children: Toddlers aged 12 to 23 months and Children aged 2 to 5 years must have a Z-score of ≥ -2 SD on the Weight-for-height table of the WHO Child Growth Standards Informed consent obtained For adults: Informed consent form has been signed and dated by the subject and by an independent witness, if required by local regulations For toddlers, children, and adolescents: Assent form has been signed and dated by the subject (for subjects 7 to 17 years of age), and informed consent form has been signed and dated by the parent(s) or legally acceptable representative and by an independent witness, if required by local regulations Able to attend all scheduled visits and to comply with all trial procedures For adults: Able to attend all scheduled visits and to comply with all trial procedures For toddlers, children, and adolescents: Participants and parent / legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures For Toddlers: All toddlers must be due to receive an age-recommended RPV on D0 - - - - Exclusion Criteria: Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche, or post-menopausal for at least 1 year, or surgically sterile Participation at the time of study enrollment (or in the 4 weeks preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure Receipt of any vaccine in the 4 weeks (28 days) preceding the IMP or planned receipt of any vaccine in the 4 weeks following vaccination except for oral poliovirus vaccine (OPV) in India, received during national immunization days. In India, OPV may be received with a gap of at least 2 weeks before the IMP. This exception includes monovalent and bivalent OPV. Previous vaccination against meningococcal disease with either the IMP or another vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup containing vaccine) Receipt of immune globulins, blood or blood-derived products in the past 3 months Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) History of meningococcal infection, confirmed either clinically, serologically, or microbiologically At high risk for meningococcal infection during the trial (specifically, but not limited to, subjects with persistent complement deficiency, with anatomic or functional asplenia, or subjects traveling to countries with high endemic or epidemic disease) Known systemic hypersensitivity to latex or to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances Verbal report of thrombocytopenia, as reported by the subject or the subject's parent / legally acceptable representative, contraindicating intramuscular vaccination in the Investigator's opinion Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion Personal history of Guillain-Barré syndrome Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine within 10 years of the proposed study vaccination Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Current alcohol abuse or drug addiction Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion Any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives. Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination, febrile illness (temperature ≥ 38.0°C), persistent diarrhea, vomiting. A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study

Ages Eligible for Study
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Minimum Age: 12 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
Interventional Model Description: Toddlers (open-label), children, adolescents and adults aged 12 months and above are enrolled in India, and children and adolescents aged 2 to 17 years are included in RSA. The older populations (adults) are recruited before initiating the study in children and adolescents younger than 17 years of age in India.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>MenACYW conjugate vaccine, 1 vaccination, adults in India aged 18 to 55 years | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine<br>* Pharmaceutical form: solution for injection; Route of administration: intramuscular, 0.5 mL<br>* Other names: MenACYW conjugate vaccine;|
| Active Comparator: Group 2<br>Menactra® conjugate vaccine, 1 vaccination, adults in India aged 18 to 55 years | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W-135) diphtheria toxoid conjugate vaccine<br>* Pharmaceutical form: sterile aqueous solution; Route of administration: intramuscular, 0.5 mL<br>* Other names: Menactra®;|
| Experimental: Group 3<br>MenACYW conjugate vaccine, 1 vaccination, adults in India aged ≥ 56 years | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine<br>* Pharmaceutical form: solution for injection; Route of administration: intramuscular, 0.5 mL<br>* Other names: MenACYW conjugate vaccine;|
| Active Comparator: Group 4<br>Quadri Meningo™, 1 vaccination, adults in India aged ≥ 56 years | Biological: Meningococcal polysaccharide (serogroups A, C, Y and W-135) vaccine<br>* Pharmaceutical form: reconstituted solution for injection; Route of administration: intramuscular, 0.5 mL<br>* Other names: Quadri Meningo™;|
| Experimental: Group 5<br>MenACYW conjugate vaccine, 1 vaccination, children and adolescents in India aged 2 to 17 years | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine<br>* Pharmaceutical form: solution for injection; Route of administration: intramuscular, 0.5 mL<br>* Other names: MenACYW conjugate vaccine;|
| Active Comparator: Group 6<br>Menactra®, 1 vaccination, children and adolescents in India aged 2 to 17 years | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W-135) diphtheria toxoid conjugate vaccine<br>* Pharmaceutical form: sterile aqueous solution; Route of administration: intramuscular, 0.5 mL<br>* Other names: Menactra®;|
| Experimental: Group 7<br>MenACYW conjugate vaccine, 1 vaccination, children and adolescents in RSA aged 2 to 17 years | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine<br>* Pharmaceutical form: solution for injection; Route of administration: intramuscular, 0.5 mL<br>* Other names: MenACYW conjugate vaccine;|
| Active Comparator: Group 8<br>Menactra®, 1 vaccination, children and adolescents in RSA aged 2 to 17 years | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W-135) diphtheria toxoid conjugate vaccine<br>* Pharmaceutical form: sterile aqueous solution; Route of administration: intramuscular, 0.5 mL<br>* Other names: Menactra®;|
| Experimental: Group 9<br>MenACYW conjugate vaccine and age-recommended routine pediatric vaccine(s), toddlers aged 12 to 23 months in India | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W) tetanus toxoid conjugate vaccine<br>* Pharmaceutical form: solution for injection; Route of administration: intramuscular, 0.5 mL<br>* Other names: MenACYW conjugate vaccine;Biological: Hepatitis A vaccine<br>* Pharmaceutical form: Suspension for injection in prefilled syringe Route of administration: Intramuscular, 0.5 mL<br>* Other names: Avaxim 80®;Biological: Measles, Mumps, and Rubella Virus Vaccine (MMR)<br>* Pharmaceutical form: Lyophilized powder for injection Route of administration: Subcutaneous or Intramuscular, 0.5 mL<br>* Other names: Priorix™;Biological: Pneumococcal 13-valent conjugate vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>* Other names: Prevnar 13®;Biological: DTwP-HepB-Hib-IPV vaccine<br>* Pharmaceutical form: Solution for injection Route of administration: Intramuscular, 0.5 mL<br>* Other names: Shan6® or EasySixTM;Biological: Varicella vaccine<br>* Pharmaceutical form: Sterile powder and diluent for injection in prefilled syringe Subcutaneous, 0.5 mL Route of administration: Pharmaceutical form:<br>* Other names: Varilrix®;|
| Active Comparator: Group 10<br>Age-recommended routine pediatric vaccine(s) (RPV) only, toddlers aged 12 to 23 months in India | Biological: Meningococcal polysaccharide (serogroups A,C,Y and W-135) diphtheria toxoid conjugate vaccine<br>* Pharmaceutical form: sterile aqueous solution; Route of administration: intramuscular, 0.5 mL<br>* Other names: Menactra®;Biological: Hepatitis A vaccine<br>* Pharmaceutical form: Suspension for injection in prefilled syringe Route of administration: Intramuscular, 0.5 mL<br>* Other names: Avaxim 80®;Biological: Measles, Mumps, and Rubella Virus Vaccine (MMR)<br>* Pharmaceutical form: Lyophilized powder for injection Route of administration: Subcutaneous or Intramuscular, 0.5 mL<br>* Other names: Priorix™;Biological: Pneumococcal 13-valent conjugate vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular, 0.5 mL<br>* Other names: Prevnar 13®;Biological: DTwP-HepB-Hib-IPV vaccine<br>* Pharmaceutical form: Solution for injection Route of administration: Intramuscular, 0.5 mL<br>* Other names: Shan6® or EasySixTM;Biological: Varicella vaccine<br>* Pharmaceutical form: Sterile powder and diluent for injection in prefilled syringe Subcutaneous, 0.5 mL Route of administration: Pharmaceutical form:<br>* Other names: Varilrix®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W | % of participants achieving antibody titers ≥ predefined threshold of 1:8 | Day 30 after vaccination | 
| Antibody titers ≥ 1:8 against meningococcal serogroups A, C, Y, and W | % of participants achieving antibody titers measured by hSBA ≥ predefined threshold of 1:8. | D30 after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA | Antibody titers are measured by hSBA and summarized as geometric mean titers (GMTs) | Day 0 and Day 30 after vaccination | 
| Antibody titers against meningococcal serogroups A, C, Y, and W measured by rSBA | Antibody titers are measured by rSBA and summarized as GMTs | Day 0 and Day 30 after vaccination | 
| Antibody titers ≥ several pre-defined thresholds against meningococcal serogroups A, C, Y, and W measured by hSBA | Antibody titers are measured by hSBA and summarized as % of participants achieving antibody titers ≥ predefined thresholds | Day 0 and Day 30 after vaccination | 
| Antibody titers ≥ several pre-defined thresholds against meningococcal serogroups A, C, Y, and W measured by rSBA | Antibody titers are measured by rSBA and summarized as % of participants achieving antibody titers ≥ predefined thresholds | Day 0 and Day 30 after vaccination | 
| Antibody titers against meningococcal serogroups A, C, Y, and W | Antibody titers are measured by hSBA and summarized as geometric mean titers (GMTs) | D0 and D30 after vaccination | 
| Antibody titers against meningococcal serogroups A, C, Y, and W (in a subset) | Antibody titers are measured by serum bactericidal assay using baby rabbit complement (rSBA) and summarized as GMTs | D0 and D30 after vaccination | 
| Antibody titers ≥ several pre-defined thresholds against meningococcal serogroups A, C, Y, and W | Antibody titers are measured by hSBA and summarized as % of participants achieving antibody titers ≥ predefined thresholds | D0 and D30 after vaccination | 
| Antibody titers ≥ several pre-defined thresholds against meningococcal serogroups A, C, Y, and W (in a subset) | Antibody titers are measured by rSBA and summarized as % of participants achieving antibody titers ≥ predefined thresholds | D0 and D30 after vaccination |