A Study on the Safety, Tolerability and Immune Response of Meningococcal Combined ABCWY Vaccine in Healthy Infants

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and immunogenicity of the combined meningococcal groups A, B, C, W and Y (MenABCWY-2Gen) vaccine intended to protect against invasive meningococcal disease (IMD) caused by all 5 meningococcal serogroups, in healthy infants 2 months of age (MoA) at enrolment.

Official Title
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A Phase II, Randomized, Partially Blinded Study to Assess the Safety, Tolerability and Immunogenicity of Meningococcal Combined ABCWY Vaccine When Administered to Healthy Infants

Conditions
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Infections, Meningococcal

Intervention / Treatment
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* Combination Product: MenABCWY-2Gen low dose vaccine
* Combination Product: MenABCWY-2Gen high dose vaccine
* Combination Product: MenABCWY-1Gen vaccine
* Combination Product: MenB vaccine
* Combination Product: MenACWY-TT vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure. Healthy participants as established by medical history and clinical examination before entering into the study. A male or female between, and including, 55 and 89 days of age (approximately 2 MoA) at the time of the first study vaccination. Born after a gestation period of ≥37 weeks, with a birth weight ≥2.5 kg. Exclusion Criteria: Medical conditions Current or previous, confirmed or suspected disease caused by N. meningitidis. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection from birth. Progressive, unstable or uncontrolled clinical conditions. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. Any neuroinflammatory disorders, congenital and peripartum neurological conditions, encephalopathies, seizures. Congenital or peripartum disorders resulting in a chronic condition Major congenital defects, as assessed by the investigator. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s)/product(s). Hypersensitivity, including allergy, to any component of vaccines, including diphtheria toxoid (CRM197) and latex medicinal products or medical equipment whose use is foreseen in this study. Abnormal function or modification of the immune system resulting from: Autoimmune disorders or immunodeficiency syndromes. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days starting from birth until Visit 5. This will mean prednisone equivalent ≥0.5 mg/kg/day with maximum 20 mg/day. Inhaled and topical steroids are allowed. Administration of antineoplastic and immunomodulating agents or radiotherapy from birth. Administration of long-acting immune-modifying drugs at any time during the study period. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. Prior/Concomitant therapy Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccines from birth, or planned use during the study period. Previous vaccination with any meningococcal vaccine. Administration of immunoglobulins and/or any blood products or plasma derivatives from birth or planned administration during the study period until Visit 5. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting from birth until Visit 5. For corticosteroids, this will mean prednisone equivalent ≥0.5 mg/kg/day with maximum 20 mg/day. Inhaled and topical steroids are allowed. Prior/Concurrent clinical study experience Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or medical device). Other exclusions Child in care. Study personnel as an immediate family or household member. For contraindications to administering routine vaccines foreseen in the study, refer to their approved product label/package insert.

Ages Eligible for Study
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Minimum Age: 55 Days
Maximum Age: 89 Days

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABCWY-2Gen low dose Group<br>Participants receive 3 doses of the MenABCWY-2Gen low dose vaccine. | Combination Product: MenABCWY-2Gen low dose vaccine<br>* MenABCWY-2Gen low dose vaccine is administered intramuscularly in the upper thigh region of the right leg as 3 doses to participants in study Part I, Step 1 and study Part II.<br>|
| Active Comparator: MenB+MenACWY-TT Group<br>Participants receive 3 doses of both the meningococcal group B (MenB) vaccine and the meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine. | Combination Product: MenB vaccine<br>* MenB vaccine is administered intramuscularly in the upper thigh region of the right leg as 3 doses to participants in study Part I, Step 1 and Step 2 and study Part II.<br>* Other names: Bexsero;Combination Product: MenACWY-TT vaccine<br>* MenACWY-TT vaccine is administered intramuscularly in the lower thigh region of the right leg as 3 doses to participants in study Part I, Step 1 and Step 2 and study Part II.<br>* Other names: Nimenrix;|
| Experimental: ABCWY-2Gen high dose Group<br>Participants receive 3 doses of the MenABCWY-2Gen high dose vaccine in. | Combination Product: MenABCWY-2Gen high dose vaccine<br>* MenABCWY-2Gen high dose vaccine is administered intramuscularly in the upper thigh region of the right leg as 3 doses to participants in study Part I, Step 2 and study Part II.<br>|
| Experimental: ABCWY-1Gen Group<br>Participants receive 3 doses of the MenABCWY-1Gen vaccine. | Combination Product: MenABCWY-1Gen vaccine<br>* MenABCWY-1Gen vaccine is administered intramuscularly in the upper thigh region of the right leg as 3 doses to participants in study Part II.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with solicited administration site events | The solicited administration site events include tenderness, erythema, induration and swelling. | During the 7 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1 and 61 and Day 301) | 
| Percentage of participants with solicited systemic events | The solicited systemic events include fever, irritability/fussiness, loss of appetite, drowsiness, vomiting and diarrhoea. Fever is defined as temperature >38.0°C/100.4°F. The preferred location for measuring temperature will be axillary. | During the 7 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1 and 61 and Day 301) | 
| Percentage of participants with any unsolicited adverse events (AEs), including all medically attended adverse events (MAEs), serious adverse events (SAEs), AEs leading to withdrawal, and adverse events of special interest (AESIs) | Unsolicited AEs includes any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. MAEs are defined as symptoms or illnesses requiring a hospitalization, or an emergency room visit, or visit to/by a health care provider. An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. AESIs are predefined (serious or non-serious) AEs of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation in order to characterize and understand it. | During the 30 days (including the day of vaccination) after each vaccination (vaccines administered on Day 1 and 61 and Day 301) | 
| Percentages of participants with MAEs, SAEs, AEs leading to withdrawal, and AESIs | MAEs are defined as symptoms or illnesses requiring a hospitalization, or an emergency room visit, or visit to/by a health care provider. An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. AESIs are predefined (serious or non-serious) AEs of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation in order to characterize and understand it. | During the study period (Day 1 through Day 481) | 
| Percentage of participants with human serum bactericidal assay (hSBA) titers ≥ lower limit of quantitation (LLOQ) for each serogroup B indicator strain | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine is evaluated by measuring bactericidal activity using an hSBA against all serogroup B indicator strains. | At 1 month after the second vaccination (Day 91) | 
| Percentage of participants with hSBA titers ≥ LLOQ for each serogroup B indicator strain | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine is evaluated by measuring bactericidal activity using an hSBA against all serogroup B indicator strains. | At pre-third vaccination (Day 301) | 
| Percentage of participants with hSBA titers ≥ LLOQ for each serogroup B indicator strain | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine is evaluated by measuring bactericidal activity using an hSBA against all serogroup B indicator strains. | At 1 month after the third vaccination (Day 331) | 
| hSBA geometric mean titers (GMTs) for each serogroup B indicator strain | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMTs. For each serogroup B indicator strain 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenB, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way Analysis of Variance (ANOVA) with factors for arms and center. | At 1 month after the second vaccination (Day 91) | 
| hSBA GMTs for each serogroup B indicator strain | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMTs. For each serogroup B indicator strain 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenB, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center. | At pre-third vaccination (Day 301) | 
| hSBA GMTs for each serogroup B indicator strain | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMTs. For each serogroup B indicator strain 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenB, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center. | At 1 month after the third vaccination (Day 331) | 
| Within group hSBA geometric mean ratios (GMRs) for each serogroup B indicator strain | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMRs. Within-group ratios of hSBA GMTs against each of the N.meningitidis serogroup B indicator strain at Day 331 compared to Day 301. | At 1 month after the third vaccination (Day 331) compared to pre-third vaccination (Day 301) | 
| Percentage of participants with hSBA titers ≥ LLOQ for each A, C, W and Y serogroup | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine is evaluated by measuring bactericidal activity using an hSBA against serogroups A, C, W and Y. The percentages of participants with hSBA titers ≥ LLOQ and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method are calculated. | At 1 month after the second vaccination (Day 91) | 
| Percentage of participants with hSBA titers ≥ LLOQ for each A, C, W and Y serogroup | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine is evaluated by measuring bactericidal activity using an hSBA against serogroups A, C, W and Y. The percentages of participants with hSBA titers ≥ LLOQ and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method are calculated. | At pre-third vaccination (Day 301) | 
| Percentage of participants with hSBA titers ≥ LLOQ for each A, C, W and Y serogroup | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine is evaluated by measuring bactericidal activity using an hSBA against serogroups A, C, W and Y. The percentages of participants with hSBA titers ≥ LLOQ and the corresponding exact 2-sided 95% CIs based on Clopper-Pearson method are calculated. | At 1 month after the third vaccination (Day 331) | 
| hSBA GMTs for each A, C, W and Y serogroup | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine against serogroups A, C, W and Y is determined using hSBA GMTs. For each A, C, W, and Y serogroup 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenACWY-TT, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center. | At 1 month after the second vaccination (Day 91) | 
| hSBA GMTs for each A, C, W and Y serogroup | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine against serogroups A, C, W and Y is determined using hSBA GMTs. For each A, C, W, and Y serogroup 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenACWY-TT, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center. | At pre-third vaccination (Day 301) | 
| hSBA GMTs for each A, C, W and Y serogroup | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine against serogroups A, C, W and Y is determined using hSBA GMTs. For each A, C, W, and Y serogroup 90% CIs for the GMTs ratio between ABCWY-2Gen low dose/ ABCWY-2Gen high dose and MenACWY-TT, is created by exponentiating (base 10) the least squares means and the lower and upper limits of the 90% CIs of the log transformed titers (base 10) obtained from a 2-way ANOVA with factors for arms and center. | At 1 month after the third vaccination (Day 331) | 
| Within group hSBA GMRs for each A, C, W and Y serogroup | The immune response to the MenABCWY-2Gen vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenACWY-TT vaccine against serogroups A, C, W and Y is determined using hSBA GMRs. Within-group ratios of hSBA GMTs against each of the N.meningitidis A, C, W and Y serogroups at Day 331 compared to Day 301. | At 1 month after the third vaccination (Day 331) compared to pre-third vaccination (Day 301) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MenABCWY-2Gen, MenABCWY-1Gen, Bexsero, Nimenrix, Safety, Tolerability, Immunogenicity, Invasive Meningococcal Disease, Healthy infants