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| ID | Type | Description | Link |
|---|---|---|---|
| UM1AI148689 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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Infants aged 9 months will be randomized to receive a meningococcal vaccine at 9 months or 15 months. Infants randomized to the 9-month age group will be further randomized in a 2:1 ratio to receive a single dose of the experimental meningococcal vaccine (NmCV-5) or a single dose of the comparator meningococcal vaccine (MenACWY-TT). Prospectively identified and consented infants randomized to the 15-month age group will return when aged 15 months and will be randomized in a 2:1 ratio to receive a single dose of NmCV-5 or a single dose of MenACWY-TT.
Meningococcal meningitis, caused by invasive strains of Neisseria meningitidis, is a major public health concern because of its considerable morbidity and mortality in sub-Saharan Africa. Case fatality during meningococcal meningitis epidemics can surpass 15%, and rates of permanent sequelae among meningitis survivors in Africa are twice as high as they are in high income countries. Because of the fulminant clinical course of invasive bacterial meningitis and difficulties in access to care in the African meningitis belt, prevention by vaccination is the optimal way to reduce meningococcal meningitis morbidity and mortality. Before 2010, serogroup A meningococcal strains were routinely responsible for the majority (70-96%) of invasive meningococcal disease in sub-Saharan Africa. And annual epidemic could be associated with an incidence of meningococcal disease which could range between 100-1000 cases per 100,000 persons in any given year.
Progressive introduction of MenAfriVac since 2010 has resulted in a substantial reduction in cases of serogroup A meningococcal disease. However, regular large-scale epidemics due to serogroups C, W and X remain common in the African meningitis belt. An affordable and scalable pentavalent meningococcal conjugate vaccine (NmCV-5) has been developed by Serum Institute of India Pvt. Ltd. (SIIPL), the manufacturer of MenAfriVac. NmCV-5 is designed to protect against serogroups A, C, W, Y and X. The immediate goal for the clinical development of NmCV-5 is for WHO Pre-Qualification (WHO-PQ), to enable the vaccine to be used in the Meningitis Belt of sub-Saharan Africa.
This trial will evaluate a single dose of NmCV-5 administered at either 9 months or 15 months of age, time points in the Expanded Program on Immunization (EPI) schedule when meningococcal vaccine is most likely to be administered. Infants aged 9 months will be randomized to receive a meningococcal vaccine at 9 months or 15 months. Infants aged 9 months (eligibility 9-11 months) and randomized to the 9-month age group will be randomized in a 2:1 ratio to receive a single dose of NmCV-5 or a single dose of MenACWY-TT. Prospectively identified and consented infants randomized to the 15-month age group will return when aged 15 months (eligibility 15-17 months) and will be randomized in a 2:1 ratio to receive a single dose of NmCV-5 or a single dose of MenACWY-TT. "Enhanced" EPI vaccines will be co-administered and will consist of 2-doses of a measles-containing vaccine administered at 9 months and 15 months and a single dose of yellow fever vaccine administered at 9 months.
This study protocol is designed to provide evidence that concomitant vaccination with NmCV-5 will not significantly affect the immune responses of infants to their normally scheduled EPI vaccines. This study has been specifically designed to provide information at two distinct timepoints, 9 months and 15 months. The current Mali EPI schedule consists of a measles only vaccine, yellow fever vaccine, and MenA vaccine at 9 months of age; there is no 15 months of age EPI vaccine visit and typically only a single dose of a measles-containing vaccine is administered. However, to satisfy the conditions for WHO-PQ, study participants will receive two doses of a measles-containing vaccine, at 9-months and 15-months. Furthermore, the noninferiority evaluation must include an assessment of the rubella vaccine responses. These modifications to the standard Malian EPI schedule provide a level-of-care that is higher than the current standard-of-care for the general population. Within the context of this study, the researchers will refer to this as an "enhanced" EPI schedule.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vaccination at 9 months of age with NmCV-5 | Experimental | Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 9 months of age, while receiving the current Mali EPI schedule of vaccines. |
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| Vaccination at 9 months of age with MenACWY-TT | Active Comparator | Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 9 months of age, while receiving the current Mali EPI schedule of vaccines. |
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| Vaccination at 15 months of age with NmCV-5 | Experimental | Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 15 months of age, while receiving the current Mali EPI schedule of vaccines. |
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| Vaccination at 15 months of age with MenACWY-TT | Active Comparator | Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 15 months of age, while receiving the current Mali EPI schedule of vaccines. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NmCV-5 | Biological | NmCV-5 is a pentavalent meningococcal (A, C, Y, W, X) polysaccharideconjugate vaccine composed of capsularpolysaccharides (PS) from Neisseria meningitidis serogroups A, C, Y, W, and X individually conjugated to a protein carrier, either mutant diphtheria toxoid (CRM197) or tetanus toxoid (TT). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Seroprotection for Meningitis Serogroups A, C, W and Y | Null hypothesis: The immune response to meningitis serogroup "S" at Day 29 elicited by one dose of NmCV-5 is inferior to the immune response elicited by one dose of MenACWY-TT. Alternative hypothesis: The immune response to meningitis serogroup "S" at Day 29 elicited by one dose of NmCV-5 is non-inferior, by a pre-specified margin, to the immune response elicited by one dose of MenACWY-TT, where "S" denotes one of the meningitis serogroups: A, C, W or Y. Endpoints are the seroprotective response at Day 29 to serogroups A, C, W and Y in the NmCV-5 arm and seroprotective response at Day 29 to serogroups A, C, W and Y in the MenACWY-TT arm with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100). | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Number of Participants With Seroprotection for Meningitis Serogroup X (NmCV-5) vs Lowest Comparator (MenACWY-TT) | Null hypothesis: At Day 29, the immune response to meningitis serogroup X elicited by one dose of NmCV-5 is inferior to the lowest immune response (among meningitis serogroups A, C, W or Y) elicited by one dose of MenACWY-TT. Alternative hypothesis: At Day 29, the immune response to meningitis serogroup X elicited by one dose of NmCV-5 is non-inferior, by a pre-specified margin, to the lowest immune response (among meningitis serogroups A, C, W or Y) elicited by one dose of MenACWY-TT. Endpoints are the seroprotective response to serogroup X in the NmCV-5 arm and the minimum seroprotective response among serogroups A, C, W and Y in the MenACWY-TT arm at Day 29 with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months). Proportions and difference in proportions are reported as percentages (number of infants per 100). | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAE) | To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all Serious Adverse Events (SAE) occurring during the first 6 months of the follow-up period after meningococcal vaccination are reported. Endpoints are the number of participants with unsolicited adverse events that are reported as Serious Adverse Events (SAEs) according to ICH/GCP guidelines or the study protocol collected from the time of Step 2 randomization and vaccination and with date of event onset up to and including Study Day 181. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wilbur Chen, MD, MS | University of Maryland, Baltimore | Study Chair |
| Karen Kotloff, MD | University of Maryland, Baltimore | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre pour le Developpement des Vaccins du Mali | Bamako | Mali |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40086461 | Derived | Diallo F, Haidara FC, Tapia MD, Dominguez Islas CP, Alderson MR, Hausdorff WP, Martellet L, Hosken N, Kapse D, Kulkarni PS, Townsend-Payne K, Vanni F, Posavad CM, Sow SO, Kotloff KL, Chen WH; NmCV-5 EPI study team. Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, W, Y, and X when co-administered with routine childhood vaccines at ages 9 months and 15 months in Mali: a single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2025 Mar 29;405(10484):1069-1080. doi: 10.1016/S0140-6736(25)00046-7. Epub 2025 Mar 11. | |
| 37224203 |
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1331 participants were assessed for eligibility and 6 were ineligible and excluded. 1325 participants received step 1 randomization to Group 1 (meningococcal vaccination at 9 months of age, n=602) or Group 2 (meningococcal vaccination at 15 months of age, n=723). 1202 participants received step 2 randomization to meningococcal vaccine study arm, and 123 Group 2 participants were excluded due to lost to follow-up or ineligibility or Group 2 target (n=600) met.
Participants were recruited in Mali, enrollment began March 24, 2022, and all follow up at Day 29 was complete by March 10, 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vaccination at 9 Months of Age With NmCV-5 | Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 9 months of age, while receiving concomitant EPI vaccines. NmCV-5: NmCV-5 is a pentavalent meningococcal (A, C, Y, W, X) polysaccharideconjugate vaccine composed of capsularpolysaccharides (PS) from Neisseria meningitidis serogroups A, C, Y, W, and X individually conjugated to a protein carrier, either mutant diphtheria toxoid (CRM197) or tetanus toxoid (TT). |
| FG001 | Vaccination at 9 Months of Age With MenACWY-TT | Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 9 months of age, while receiving concomitant EPI vaccines. MenACWY-TT: MenACWY-TT (the comparator meningococcal vaccine) is a WHO-PQ quadrivalent meningococcal (A, C, Y, W) polysaccharide-conjugate vaccine manufactured by Pfizer. |
| FG002 | Not Vaccinated But Randomized to Vaccination at 15 Months of Age | Infant participants receiving step 1 randomization to Group 2 (meningococcal vaccination at 15 months of age) and discontinued from the study prior to step 2 randomization and meningococcal vaccination because Group 2 vaccination target was met. |
| FG003 | Vaccination at 15 Months of Age With NmCV-5 | Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 15 months of age, while receiving concomitant EPI vaccines. NmCV-5: NmCV-5 is a pentavalent meningococcal (A, C, Y, W, X) polysaccharideconjugate vaccine composed of capsularpolysaccharides (PS) from Neisseria meningitidis serogroups A, C, Y, W, and X individually conjugated to a protein carrier, either mutant diphtheria toxoid (CRM197) or tetanus toxoid (TT). |
| FG004 | Vaccination at 15 Months of Age With MenACWY-TT | Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 15 months of age, while receiving concomitant EPI vaccines. MenACWY-TT: MenACWY-TT (the comparator meningococcal vaccine) is a WHO-PQ quadrivalent meningococcal (A, C, Y, W) polysaccharide-conjugate vaccine manufactured by Pfizer. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Step 1 Randomization |
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| Step 2 Randomization |
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Two participants refused the meningococcal vaccination (1 participant in each vaccine study arm in Group 1, meningococcal vaccination at 9 months of age) and were excluded from the mITT analysis set.
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| ID | Title | Description |
|---|---|---|
| BG000 | Vaccination at 9 Months of Age With NmCV-5 | Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 9 months of age, while receiving concomitant EPI vaccines. NmCV-5: NmCV-5 is a pentavalent meningococcal (A, C, Y, W, X) polysaccharideconjugate vaccine composed of capsularpolysaccharides (PS) from Neisseria meningitidis serogroups A, C, Y, W, and X individually conjugated to a protein carrier, either mutant diphtheria toxoid (CRM197) or tetanus toxoid (TT). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Seroprotection for Meningitis Serogroups A, C, W and Y | Null hypothesis: The immune response to meningitis serogroup "S" at Day 29 elicited by one dose of NmCV-5 is inferior to the immune response elicited by one dose of MenACWY-TT. Alternative hypothesis: The immune response to meningitis serogroup "S" at Day 29 elicited by one dose of NmCV-5 is non-inferior, by a pre-specified margin, to the immune response elicited by one dose of MenACWY-TT, where "S" denotes one of the meningitis serogroups: A, C, W or Y. Endpoints are the seroprotective response at Day 29 to serogroups A, C, W and Y in the NmCV-5 arm and seroprotective response at Day 29 to serogroups A, C, W and Y in the MenACWY-TT arm with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100). | All participants included in the Per Protocol (PP) Analysis Set which includes eligible participants receiving step 1 and 2 randomizations, the randomized meningococcal vaccination in the appropriate age group window with the scheduled EPI vaccinations, and who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory. | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
Serious adverse events (SAEs) are recorded from the time of enrollment to Study Day 181. SAE follow-up time was approximately 6 months for participants receiving meningococcal vaccination at 9 months of age and for participants in Group 2 but not receiving meningococcal vaccination. SAE follow-up time was approximately 12 months for participants receiving vaccination at 15 months of age. Other non-serious AEs are reported from study vaccination through 28 days after vaccination(mITT population).
SAEs were assessed for all 1325 participants who were enrolled and received step 1 randomization to Group 1 (9 months of age, n=602) or Group 2 (15 months of age, n=723, with n=600 further randomized and receiving meningococcal vaccine and n=123 not randomized and discontinued from the study). These 123 participants were followed for SAEs only during the pre-dosing period prior to step 2 randomization. Participants were routinely assessed for AEs at follow-up visits (Day 29, Day 181).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vaccination at 9 Months of Age With NmCV-5 | Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 9 months of age, while receiving concomitant EPI vaccines. NmCV-5: NmCV-5 is a pentavalent meningococcal (A, C, Y, W, X) polysaccharideconjugate vaccine composed of capsularpolysaccharides (PS) from Neisseria meningitidis serogroups A, C, Y, W, and X individually conjugated to a protein carrier, either mutant diphtheria toxoid (CRM197) or tetanus toxoid (TT). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wilbur H. Chen, M.D., M.S., FACP, FIDSA | University of Maryland School of Medicine | 410-706-5328 | wchen@som.umaryland.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 23, 2023 | Feb 29, 2024 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 2, 2023 | Feb 29, 2024 | SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 9, 2021 | May 3, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D008581 | Meningitis |
| ID | Term |
|---|---|
| D000090862 | Neuroinflammatory Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000717934 | NmCV-5 vaccine |
| C576777 | tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine |
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| MenACWY-TT | Biological | MenACWY-TT (the comparator meningococcal vaccine) is a WHO-PQ quadrivalent meningococcal (A, C, Y, W) polysaccharide-conjugate vaccine manufactured by Pfizer. |
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| Measured from time of meningococcal vaccination to Study Day 181 or early study termination, whichever is earlier. Follow-up time to Study Day 181 visit was a mean (s.d.) of 180.8 (3.0) days. |
| Number of Participants With Solicited Adverse Events (Reactogenicity) | To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all solicited AEs occurring during a 7-day follow-up period after meningococcal vaccination are reported. Solicited AEs include injection site (local) events (erythema/redness, induration/swelling, pain and/or tenderness) and systemic events (irritability, drowsiness/lethargy, decrease eating/anorexia, vomiting, fever (axillary), and feverish). Endpoints are the number of participants with solicited adverse events collected from about 30 minutes after meningococcal vaccination to Study Day 8 (7 days after vaccination). NOTE: Capture of data for symptom Feverish began on June 15, 2022, so some participants were not assessed for this symptom. Also, Fever (Axillary) is objectively measured by oral temperature and Feverish is a subjective observation from a parent who feels their infant has a raised temperature but not verified by thermometer. | Measured from about 30 minutes after meningococcal vaccination to Study Day 8 (7 days) for all participants. |
| Number of Participants With Unsolicited Adverse Events | To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all unsolicited AEs occurring through 28 days after meningococcal vaccination are reported. Unsolicited AEs include AEs reported in scheduled or interim (unscheduled) visits after receipt of meningitis vaccination and with date of onset up to and including Study Day 29. Endpoints are the number of participants reporting at least one unsolicited adverse event (overall and by MedDRA preferred term). | Measured from time of meningococcal vaccination to Study Day 29 (28 days) for all participants. |
| Number of Participants With Seroprotection for Meningitis Serogroup X | Null hypothesis: The immune response to meningitis serogroup X at Day 29 elicited by one dose of NmCV-5 is not superior to the immune response elicited by one dose of MenACWY-TT, Alternative hypothesis: The immune response to meningitis serogroup X at Day 29 elicited by one dose of NmCV-5 is superior, by a pre-specified margin, to the immune response elicited by one dose of MenACWY-TT. Endpoints are the seroprotective response to serogroup X in the NmCV-5 arm at Day 29 and the seroprotective response defined to serogroup X in the MenACWY-TT arm at Day 29 with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Superiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100). | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Number of Participants With Seropositive Response to Measles Vaccine | Null hypothesis: The immune response to measles at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to measles at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seropositive responses to measles vaccine at Day 29 post vaccination, defined as anti-measles IgG concentration >200 mIU/mL. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100). | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Number of Participants With Seropositive Response to Rubella Vaccine | Null hypothesis: The immune response to rubella at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to rubella at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seropositive responses to rubella vaccine at Day 29 post vaccination, defined as anti-rubella IgG concentration >20 IU/mL. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100). | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Number of Participants With Seroprotective Response to Yellow Fever Vaccine | Null hypothesis: The immune response to yellow fever at Day 29 elicited by the yellow fever vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the yellow fever vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to yellow fever at Day 29 elicited by the yellow fever vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the yellow fever vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seroprotective responses to yellow fever vaccine at Day 29 post vaccination, defined as yellow fever neutralizing antibody titers ≥10. Non-inferiority comparisons are made between study vaccination arms within the 9 months study age group only. Proportions and difference in proportions are reported as percentages (number of infants per 100). | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Geometric Mean of rSBA Titers for Meningitis Serogroups A, C, W, Y and X | For each study age group (9 months and 15 months) and for each of the five serogroups (A, C, W, Y, and X), geometric means and 95% CIs of rSBA titers at Day 29 are calculated by study vaccination arm within each study age group, and the Geometric Mean Titer (GMT) Ratio of rSBA titers at Day 29 for NmCV-5 relative to MenACWY-TT will be estimated, along with 95% CIs. The point and interval estimates will be obtained from a back transformation of the estimated difference in means of the log-transformed rSBA titers. Endpoints are the rSBA titer values for meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29). | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Seroresponse for Meningitis Serogroups A, C, W, Y and X | To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the number and proportion of participants with seroresponse in rSBA titers at Day 29 is calculated for meningococcal serogroups A, C, W, Y and X. Endpoints are the number and percentage of participants with seroresponse in rSBA titers to meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29), where seroresponse is defined as a post-immunization (Day 29) rSBA titer of 32 or greater if the participant's pre-immunization (Baseline) rSBA titer was < 8; or a ≥ four-fold increase over baseline at Day 29 post-immunization if the participant's pre-immunization rSBA titer was ≥ 8. Seroresponse is calculated for each study vaccination arm within each study age group (9 months or 15 months of age). Proportions are reported as percentages (number of infants per 100). | Measured from time of blood sample collection just prior to meningococcal vaccination at Day 1 visit to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Geometric Mean Fold Rise (GMFR) for Meningitis Serogroups A, C, W, Y and X | To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the Geometric Mean Fold Rise (GMFR) from baseline to Day 29 of rSBA titers to meningococcal serogroups A, C, W, Y and X is estimated, with 95% CI. Endpoints are the rSBA titer values for meningococcal serogroups A, C, W, Y and X from samples collected at Visit 1 (Day 1) and Visit 3 (Day 29). The point and interval estimates will be obtained from a back transformation of the estimated mean difference of the log-transformed rSBA titers. | Measured from time of blood sample collection just prior to meningococcal vaccination at Day 1 visit to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Number of Participants With rSBA Titers ≥ 128 for Meningitis Serogroups A, C, W, Y and X | To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the number and proportion of participants with rSBA titers ≥ 128 at Day 29 is calculated for meningococcal serogroups A, C, W, Y and X. Endpoints are the number and proportion of participants with rSBA titers ≥ 128 for meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29). This is calculated for each study vaccination arm within each study age group (9 months or 15 months of age). Proportions are reported as percentages (number of infants per 100). | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
| Derived |
| Stephens DS. Global Control of Meningococcal Disease. N Engl J Med. 2023 May 25;388(21):2003-2005. doi: 10.1056/NEJMe2301698. No abstract available. |
| COMPLETED |
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| NOT COMPLETED |
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| BG001 | Vaccination at 9 Months of Age With MenACWY-TT | Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 9 months of age, while receiving concomitant EPI vaccines. MenACWY-TT: MenACWY-TT (the comparator meningococcal vaccine) is a WHO-PQ quadrivalent meningococcal (A, C, Y, W) polysaccharide-conjugate vaccine manufactured by Pfizer. |
| BG002 | Vaccination at 15 Months of Age With NmCV-5 | Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 15 months of age, while receiving concomitant EPI vaccines. NmCV-5: NmCV-5 is a pentavalent meningococcal (A, C, Y, W, X) polysaccharideconjugate vaccine composed of capsularpolysaccharides (PS) from Neisseria meningitidis serogroups A, C, Y, W, and X individually conjugated to a protein carrier, either mutant diphtheria toxoid (CRM197) or tetanus toxoid (TT). |
| BG003 | Vaccination at 15 Months of Age With MenACWY-TT | Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 15 months of age, while receiving concomitant EPI vaccines. MenACWY-TT: MenACWY-TT (the comparator meningococcal vaccine) is a WHO-PQ quadrivalent meningococcal (A, C, Y, W) polysaccharide-conjugate vaccine manufactured by Pfizer. |
| BG004 | Total | Total of all reporting groups |
| months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participant Height/Length | Mean | Standard Deviation | cm |
|
| Participant weight | Mean | Standard Deviation | kg |
|
| Participant Length-for-weight z-score | This is a WHO standardized method to classify a child's nutritional status where a Z-score of 0 (zero) represents the global population mean score of the weight divided by height for age. A Z-score of "+1" or "-1" is a value that is one standard deviation above or below the mean where Z-scores below the mean demonstrate a lower/poorer developmental/nutritional status than the rest of the world. The use of anthropometry based on this Z-score is commonly used to classify malnutrition, as follows -1 to -1.9: mild malnutrition, -2.0 to -2.9: moderate malnutrition and ≥ -3: severe malnutrition. | Mean | Standard Deviation | z-score |
|
| Participant Body Temperature | Mean | Standard Deviation | Celcius |
|
| Participant Heart Rate, Pulse | Mean | Standard Deviation | beats/minute |
|
| Participant Rate of Respiration | Mean | Standard Deviation | breaths/minute |
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|
| Primary | Number of Participants With Seroprotection for Meningitis Serogroup X (NmCV-5) vs Lowest Comparator (MenACWY-TT) | Null hypothesis: At Day 29, the immune response to meningitis serogroup X elicited by one dose of NmCV-5 is inferior to the lowest immune response (among meningitis serogroups A, C, W or Y) elicited by one dose of MenACWY-TT. Alternative hypothesis: At Day 29, the immune response to meningitis serogroup X elicited by one dose of NmCV-5 is non-inferior, by a pre-specified margin, to the lowest immune response (among meningitis serogroups A, C, W or Y) elicited by one dose of MenACWY-TT. Endpoints are the seroprotective response to serogroup X in the NmCV-5 arm and the minimum seroprotective response among serogroups A, C, W and Y in the MenACWY-TT arm at Day 29 with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months). Proportions and difference in proportions are reported as percentages (number of infants per 100). | All participants included in the Per Protocol (PP) Analysis Set which includes eligible participants receiving step 1 and 2 randomizations, the randomized meningococcal vaccination in the appropriate age group window with the scheduled EPI vaccinations, and who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory. | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
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| Secondary | Number of Participants With Serious Adverse Events (SAE) | To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all Serious Adverse Events (SAE) occurring during the first 6 months of the follow-up period after meningococcal vaccination are reported. Endpoints are the number of participants with unsolicited adverse events that are reported as Serious Adverse Events (SAEs) according to ICH/GCP guidelines or the study protocol collected from the time of Step 2 randomization and vaccination and with date of event onset up to and including Study Day 181. | All participants included in the modified intent-to-treat (mITT) Analysis Set which includes all participants who were randomized at Step 1 and Step 2 and who received a study meningitis vaccine (NmCV-5 or MenACWY-TT). | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to Study Day 181 or early study termination, whichever is earlier. Follow-up time to Study Day 181 visit was a mean (s.d.) of 180.8 (3.0) days. |
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|
|
| Secondary | Number of Participants With Solicited Adverse Events (Reactogenicity) | To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all solicited AEs occurring during a 7-day follow-up period after meningococcal vaccination are reported. Solicited AEs include injection site (local) events (erythema/redness, induration/swelling, pain and/or tenderness) and systemic events (irritability, drowsiness/lethargy, decrease eating/anorexia, vomiting, fever (axillary), and feverish). Endpoints are the number of participants with solicited adverse events collected from about 30 minutes after meningococcal vaccination to Study Day 8 (7 days after vaccination). NOTE: Capture of data for symptom Feverish began on June 15, 2022, so some participants were not assessed for this symptom. Also, Fever (Axillary) is objectively measured by oral temperature and Feverish is a subjective observation from a parent who feels their infant has a raised temperature but not verified by thermometer. | All participants included in the modified intent-to-treat (mITT) Analysis Set which includes all participants who were randomized at Step 1 and Step 2 and who received a study meningitis vaccine (NmCV-5 or MenACWY-TT). | Posted | Count of Participants | Participants | Measured from about 30 minutes after meningococcal vaccination to Study Day 8 (7 days) for all participants. |
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|
|
| Secondary | Number of Participants With Unsolicited Adverse Events | To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all unsolicited AEs occurring through 28 days after meningococcal vaccination are reported. Unsolicited AEs include AEs reported in scheduled or interim (unscheduled) visits after receipt of meningitis vaccination and with date of onset up to and including Study Day 29. Endpoints are the number of participants reporting at least one unsolicited adverse event (overall and by MedDRA preferred term). | All participants included in the modified intent-to-treat (mITT) Analysis Set which includes all participants who were randomized at Step 1 and Step 2 and who received a study meningitis vaccine (NmCV-5 or MenACWY-TT). | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to Study Day 29 (28 days) for all participants. |
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|
|
| Secondary | Number of Participants With Seroprotection for Meningitis Serogroup X | Null hypothesis: The immune response to meningitis serogroup X at Day 29 elicited by one dose of NmCV-5 is not superior to the immune response elicited by one dose of MenACWY-TT, Alternative hypothesis: The immune response to meningitis serogroup X at Day 29 elicited by one dose of NmCV-5 is superior, by a pre-specified margin, to the immune response elicited by one dose of MenACWY-TT. Endpoints are the seroprotective response to serogroup X in the NmCV-5 arm at Day 29 and the seroprotective response defined to serogroup X in the MenACWY-TT arm at Day 29 with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Superiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100). | All participants included in the Per Protocol (PP) Analysis Set which includes eligible participants receiving step 1 and 2 randomizations, the randomized meningococcal vaccination in the appropriate age group window with the scheduled EPI vaccinations, and who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory. | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
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| Secondary | Number of Participants With Seropositive Response to Measles Vaccine | Null hypothesis: The immune response to measles at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to measles at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seropositive responses to measles vaccine at Day 29 post vaccination, defined as anti-measles IgG concentration >200 mIU/mL. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100). | All participants included in the Per Protocol (PP) Analysis Set which includes eligible participants receiving step 1 and 2 randomizations, the randomized meningococcal vaccination in the appropriate age group window with the scheduled EPI vaccinations, and who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory. | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
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|
|
|
| Secondary | Number of Participants With Seropositive Response to Rubella Vaccine | Null hypothesis: The immune response to rubella at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to rubella at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seropositive responses to rubella vaccine at Day 29 post vaccination, defined as anti-rubella IgG concentration >20 IU/mL. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100). | All participants included in the Per Protocol (PP) Analysis Set which includes eligible participants receiving step 1 and 2 randomizations, the randomized meningococcal vaccination in the appropriate age group window with the scheduled EPI vaccinations, and who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory. | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
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|
|
|
| Secondary | Number of Participants With Seroprotective Response to Yellow Fever Vaccine | Null hypothesis: The immune response to yellow fever at Day 29 elicited by the yellow fever vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the yellow fever vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to yellow fever at Day 29 elicited by the yellow fever vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the yellow fever vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seroprotective responses to yellow fever vaccine at Day 29 post vaccination, defined as yellow fever neutralizing antibody titers ≥10. Non-inferiority comparisons are made between study vaccination arms within the 9 months study age group only. Proportions and difference in proportions are reported as percentages (number of infants per 100). | All Group 1 participants included in the Per Protocol (PP) Analysis Set which includes eligible participants receiving step 1 and 2 randomizations, the randomized meningococcal vaccination in the appropriate age group window with the scheduled EPI vaccinations, and who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory. | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
|
|
|
|
| Secondary | Geometric Mean of rSBA Titers for Meningitis Serogroups A, C, W, Y and X | For each study age group (9 months and 15 months) and for each of the five serogroups (A, C, W, Y, and X), geometric means and 95% CIs of rSBA titers at Day 29 are calculated by study vaccination arm within each study age group, and the Geometric Mean Titer (GMT) Ratio of rSBA titers at Day 29 for NmCV-5 relative to MenACWY-TT will be estimated, along with 95% CIs. The point and interval estimates will be obtained from a back transformation of the estimated difference in means of the log-transformed rSBA titers. Endpoints are the rSBA titer values for meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29). | All participants included in the Per Protocol (PP) Analysis Set which includes eligible participants receiving step 1 and 2 randomizations, the randomized meningococcal vaccination in the appropriate age group window with the scheduled EPI vaccinations, and who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory. | Posted | Geometric Mean | 95% Confidence Interval | rSBA titer | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
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|
|
| Secondary | Seroresponse for Meningitis Serogroups A, C, W, Y and X | To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the number and proportion of participants with seroresponse in rSBA titers at Day 29 is calculated for meningococcal serogroups A, C, W, Y and X. Endpoints are the number and percentage of participants with seroresponse in rSBA titers to meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29), where seroresponse is defined as a post-immunization (Day 29) rSBA titer of 32 or greater if the participant's pre-immunization (Baseline) rSBA titer was < 8; or a ≥ four-fold increase over baseline at Day 29 post-immunization if the participant's pre-immunization rSBA titer was ≥ 8. Seroresponse is calculated for each study vaccination arm within each study age group (9 months or 15 months of age). Proportions are reported as percentages (number of infants per 100). | All participants included in the Baseline Immunogenicity Analysis Set which includes a subset of participants randomly selected for assessment of baseline rSBA titers from blood samples collected at Day 1 (pre-vaccination). This set includes up to 150 participants from Group 1 and 198 participants from Group 2 who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory for both the Day 1 and Day 29 visit samples. | Posted | Count of Participants | Participants | Measured from time of blood sample collection just prior to meningococcal vaccination at Day 1 visit to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
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|
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| Secondary | Geometric Mean Fold Rise (GMFR) for Meningitis Serogroups A, C, W, Y and X | To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the Geometric Mean Fold Rise (GMFR) from baseline to Day 29 of rSBA titers to meningococcal serogroups A, C, W, Y and X is estimated, with 95% CI. Endpoints are the rSBA titer values for meningococcal serogroups A, C, W, Y and X from samples collected at Visit 1 (Day 1) and Visit 3 (Day 29). The point and interval estimates will be obtained from a back transformation of the estimated mean difference of the log-transformed rSBA titers. | Participants in the Baseline Immunogenicity Analysis Set include a subset of participants randomly selected for assessment of baseline rSBA titers from blood samples collected at Day 1 (pre-vaccination). This set includes up to 150 participants from Group 1 and 198 participants from Group 2 who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory for both the Day 1 and Day 29 visit samples. | Posted | Geometric Mean | 95% Confidence Interval | rSBA titer | Measured from time of blood sample collection just prior to meningococcal vaccination at Day 1 visit to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
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| Secondary | Number of Participants With rSBA Titers ≥ 128 for Meningitis Serogroups A, C, W, Y and X | To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the number and proportion of participants with rSBA titers ≥ 128 at Day 29 is calculated for meningococcal serogroups A, C, W, Y and X. Endpoints are the number and proportion of participants with rSBA titers ≥ 128 for meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29). This is calculated for each study vaccination arm within each study age group (9 months or 15 months of age). Proportions are reported as percentages (number of infants per 100). | All participants included in the Per Protocol (PP) Analysis Set which includes eligible participants receiving step 1 and 2 randomizations, the randomized meningococcal vaccination in the appropriate age group window with the scheduled EPI vaccinations, and who had a blood specimen collected in the appropriate window around the Day 29 visit and a successful rSBA value provided by the laboratory. | Posted | Count of Participants | Participants | Measured from time of meningococcal vaccination to blood sample collection at Day 29 visit. Follow-up time to Day 29 visit blood specimen collection was a mean (s.d.) of 30.9 (2.8) days. |
|
|
|
| 0 |
| 401 |
| 1 |
| 401 |
| 64 |
| 400 |
| EG001 | Vaccination at 9 Months of Age With MenACWY-TT | Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 9 months of age, while receiving concomitant EPI vaccines. MenACWY-TT: MenACWY-TT (the comparator meningococcal vaccine) is a WHO-PQ quadrivalent meningococcal (A, C, Y, W) polysaccharide-conjugate vaccine manufactured by Pfizer. | 0 | 201 | 0 | 201 | 37 | 200 |
| EG002 | Not Vaccinated But Randomized to Vaccination at 15 Months of Age | Infant participants receiving step 1 randomization to Group 2 (meningococcal vaccination at 15 months of age) and discontinued from the study prior to step 2 randomization and meningococcal vaccination because Group 2 vaccination target was met. | 1 | 123 | 1 | 123 | 0 | 0 |
| EG003 | Vaccination at 15 Months of Age With NmCV-5 | Infant participants randomized to receive the NmCV-5 meningococcal vaccination at 15 months of age, while receiving concomitant EPI vaccines. NmCV-5: NmCV-5 is a pentavalent meningococcal (A, C, Y, W, X) polysaccharideconjugate vaccine composed of capsularpolysaccharides (PS) from Neisseria meningitidis serogroups A, C, Y, W, and X individually conjugated to a protein carrier, either mutant diphtheria toxoid (CRM197) or tetanus toxoid (TT). | 0 | 400 | 2 | 400 | 16 | 400 |
| EG004 | Vaccination at 15 Months of Age With MenACWY-TT | Infant participants randomized to receive the MenACWY-TT meningococcal vaccination at 15 months of age, while receiving concomitant EPI vaccines. MenACWY-TT: MenACWY-TT (the comparator meningococcal vaccine) is a WHO-PQ quadrivalent meningococcal (A, C, Y, W) polysaccharide-conjugate vaccine manufactured by Pfizer. | 0 | 200 | 1 | 200 | 8 | 200 |
| Malaria | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA 26.1 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Impetigo | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Malaria | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Otitis media acute | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Otorrhoea | Ear and labyrinth disorders | MedDRA 26.1 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Pyoderma | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
|
Not provided
Not provided
| No |
|
| No |
|
| No |
|
|
| Participants with seroprotective response against serogroup X (NmCV-5) and serogroup Y (MenACWY-TT) |
|
|
| For the 15-months study age group, the proportion of infants with a seroprotective response to MenACWY-TT in serogroup Y is subtracted from the proportion of infants with a seroprotective response to NmCV-5 in serogroup X to determine the difference in proportions. | Difference in proportions | 1.9 | 2-Sided | 95 | 0.004 | 4.4 | Non-Inferiority | NmCV-5 will be deemed non-inferior to MenACWY-TT for serogroup X if the lower limit of the 95% confidence interval (CI) for the difference in proportion (NmCV-5 minus MenACWY-TT) excludes -0.10 (-10%). The CI is estimated using bootstrap resampling stratified by vaccine arm, and the 95% CI is estimated as the interval between the 2.5th and 97.5th percentiles of the bootstrap empirical distribution. The difference in proportions and CI are reported as percentages (number of infants per 100). |
| No |
|
| Gastroenteritis |
|
| Thermal burn |
|
| Malnutrition |
|
| No |
|
| Not Evaluated |
|
| Participants experiencing a local solicited AE |
|
| Erythema/redness |
|
| Induration/swelling |
|
| Pain and/or tenderness |
|
| Participants experiencing a systemic solicited AE |
|
| Irritability |
|
| Drowsiness/lethargy |
|
| Decrease eating/anorexia |
|
| Vomiting |
|
| Fever (axillary) |
|
| Feverish |
|
| No |
|
| Allergic cough |
|
| Bronchitis |
|
| Conjunctivitis |
|
| Diarrhoea |
|
| Gastroenteritis |
|
| Impetigo |
|
| Malaria |
|
| Nasopharyngitis |
|
| Otitis media acute |
|
| Otorrhoea |
|
| Pharyngitis |
|
| Pyoderma |
|
| Rhinitis |
|
| No |
|
| For serogroup X, the proportion of infants with a seroprotective response to MenACWY-TT is subtracted from the proportion of infants with a seroprotective response to NmCV-5 to determine the difference in proportions. | Difference in proportions | 68.4 | 2-Sided | 95 | 61.3 | 74.7 | Superiority | NmCV-5 will be deemed superior to MenACWY-TT for serogroup X if the lower limit of the 95% confidence interval for the difference in proportion (NmCV-5 minus MenACWY-TT) excludes 0.30 (30%). Confidence Intervals are calculated using the Miettinen-Nurminen method. The difference in proportions and CI are reported as percentages (number of infants per 100). |
| No |
|
| For this comparison, the proportion of infants with a seropositive response to measles vaccine in the MenACWY-TT arm is subtracted from the proportion of infants with a seropositive response to measles vaccine in the NmCV-5 arm to determine the difference in proportions. | Difference in proportions | 0.0 | 2-Sided | 95 | -1.0 | 2.1 | Non-Inferiority | The NmCV-5 co-administered MR vaccine will be deemed non-inferior to the MenACWY-TT co-administered MR vaccine in eliciting seropositive response to measles if the lower limit of the 95% confidence interval for the difference in proportions excludes -0.10 (-10%). Confidence Intervals are calculated using the Miettinen-Nurminen method. The difference in proportions and CI are reported as percentages (number of infants per 100). |
| No |
|
| For this comparison, the proportion of infants with a seropositive response to rubella vaccine in the MenACWY-TT arm is subtracted from the proportion of infants with a seropositive response to rubella vaccine in the NmCV-5 arm to determine the difference in proportions. | Difference in proportions | 0.0 | 2-Sided | 95 | -1.0 | 2.1 | Non-Inferiority | The NmCV-5 co-administered MR vaccine will be deemed non-inferior to the MenACWY-TT co-administered MR vaccine in eliciting seropositive response to rubella if the lower limit of the 95% confidence interval for the difference in proportions excludes -0.10 (-10%). Confidence Intervals are calculated using the Miettinen-Nurminen method. The difference in proportions and CI are reported as percentages (number of infants per 100). |
|
| Serogroup C |
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|
| Serogroup W |
|
|
| Serogroup Y |
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|
| Serogroup X |
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|
For serogroup A, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. |
| Ratio of geometric mean titers |
| 1.2 |
| 2-Sided |
| 95 |
| 1.0 |
| 1.6 |
NmCV-5 divided by MenACWY-TT |
| Other |
| For serogroup C, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. | Ratio of geometric mean titers | 0.5 | 2-Sided | 95 | 0.4 | 0.6 | NmCV-5 divided by MenACWY-TT | Other |
| For serogroup C, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. | Ratio of geometric mean titers | 0.4 | 2-Sided | 95 | 0.3 | 0.5 | NmCV-5 divided by MenACWY-TT | Other |
| For serogroup W, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. | Ratio of geometric mean titers | 0.9 | 2-Sided | 95 | 0.6 | 1.3 | NmCV-5 divided by MenACWY-TT | Other |
| For serogroup W, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. | Ratio of geometric mean titers | 1.6 | 2-Sided | 95 | 1.1 | 2.1 | NmCV-5 divided by MenACWY-TT | Other |
| For serogroup Y, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. | Ratio of geometric mean titers | 0.7 | 2-Sided | 95 | 0.6 | 1.0 | NmCV-5 divided by MenACWY-TT | Other |
| For serogroup Y, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. | Ratio of geometric mean titers | 1.0 | 2-Sided | 95 | 0.8 | 1.3 | NmCV-5 divided by MenACWY-TT | Other |
| For serogroup X, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. | Ratio of geometric mean titers | 1511.1 | 2-Sided | 95 | 1169.5 | 1952.4 | NmCV-5 divided by MenACWY-TT | Other |
| For serogroup X, the point and interval estimates for the Geometric Mean Titer (GMT) ratio will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMT ratio of rSBA titers at Day 29 is calculated for the NmCV-5 arm relative to the MenACWY-TT arm. | Ratio of geometric mean titers | 767.3 | 2-Sided | 95 | 553.2 | 1064.4 | NmCV-5 divided by MenACWY-TT | Other |
|
| Participants with Serogroup C Seroresponse |
|
|
| Participants with Serogroup W Seroresponse |
|
|
| Participants with Serogroup Y Seroresponse |
|
|
| Participants with Serogroup X Seroresponse |
|
|
|
| Serogroup A, Day 29 |
|
|
| Serogroup C, Day 1 |
|
|
| Serogroup C, Day 29 |
|
|
| Serogroup W, Day 1 |
|
|
| Serogroup W, Day 29 |
|
|
| Serogroup Y, Day 1 |
|
|
| Serogroup Y, Day 29 |
|
|
| Serogroup X, Day 1 |
|
|
| Serogroup X, Day 29 |
|
|
For serogroup A, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. |
| Ratio of geometric mean titers |
| 2506.9 |
| 2-Sided |
| 95 |
| 1404.0 |
| 4476.1 |
Day 29 divided by Day 1 |
| Other |
| For serogroup A, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 1179.0 | 2-Sided | 95 | 709.8 | 1958.6 | Day 29 divided by Day 1 | Other |
| For serogroup A, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 1096.2 | 2-Sided | 95 | 513.4 | 2340.6 | Day 29 divided by Day 1 | Other |
| For serogroup C, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 288.7 | 2-Sided | 95 | 212.6 | 392.0 | Day 29 divided by Day 1 | Other |
| For serogroup C, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 654.5 | 2-Sided | 95 | 385.5 | 1111.0 | Day 29 divided by Day 1 | Other |
| For serogroup C, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 287.9 | 2-Sided | 95 | 213.9 | 387.5 | Day 29 divided by Day 1 | Other |
| For serogroup C, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 834.6 | 2-Sided | 95 | 496.7 | 1402.3 | Day 29 divided by Day 1 | Other |
| For serogroup W, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 1068.4 | 2-Sided | 95 | 683.3 | 1670.6 | Day 29 divided by Day 1 | Other |
| For serogroup W, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 1933.1 | 2-Sided | 95 | 1224.7 | 3051.1 | Day 29 divided by Day 1 | Other |
| For serogroup W, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 3163.1 | 2-Sided | 95 | 2247.5 | 4451.7 | Day 29 divided by Day 1 | Other |
| For serogroup W, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 1524.1 | 2-Sided | 95 | 913.5 | 2543.0 | Day 29 divided by Day 1 | Other |
| For serogroup Y, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 799.4 | 2-Sided | 95 | 532.9 | 1199.4 | Day 29 divided by Day 1 | Other |
| For serogroup Y, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 1469.2 | 2-Sided | 95 | 995.3 | 2168.8 | Day 29 divided by Day 1 | Other |
| For serogroup Y, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 549.4 | 2-Sided | 95 | 371.8 | 811.8 | Day 29 divided by Day 1 | Other |
| For serogroup Y, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 642.6 | 2-Sided | 95 | 309.2 | 1335.9 | Day 29 divided by Day 1 | Other |
| For serogroup X, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 2630.0 | 2-Sided | 95 | 2037.6 | 3394.6 | Day 29 divided by Day 1 | Other |
| For serogroup X, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 2.0 | 2-Sided | 95 | 1.2 | 3.4 | Day 29 divided by Day 1 | Other |
| For serogroup X, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 1431.2 | 2-Sided | 95 | 905.2 | 2262.9 | Day 29 divided by Day 1 | Other |
| For serogroup X, the point and interval estimates for the Geometric Mean Fold Rise (GMFR) will be obtained from a back transformation (exponentiation) of the estimated mean ratio of the log-transformed rSBA titers. The GMFR from baseline to Day 29 of rSBA titers is calculated as Day 29 divided by Day 1. | Ratio of geometric mean titers | 1.7 | 2-Sided | 95 | 0.9 | 3.3 | Day 29 divided by Day 1 | Other |
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| Serogroup C, Participants with rSBA titer ≥ 128 |
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| Serogroup W, Participants with rSBA titer ≥ 128 |
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| Serogroup Y, Participants with rSBA titer ≥ 128 |
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| Serogroup X, Participants with rSBA titer ≥ 128 |
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| No |
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| No |
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| No |
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| No |
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| No |
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| No |
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| No |
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| No |
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