Infections, Meningococcal
Conditions
Keywords
MenACWY-7B, MenABCWY-1Gen, Bexsero, Nimenrix, Safety, Tolerability, Immunogenicity, Invasive Meningococcal Disease, Healthy infants
Brief summary
The purpose of this study is to assess the safety, tolerability and immunogenicity of the combined meningococcal groups A, B, C, W and Y (MenACWY-7b) 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.
Interventions
COMBINATION_PRODUCTMenACWY-7B low dose vaccine
MenACWY-7B low dose vaccine is administered intramuscularly in the upper thigh region of the right leg.
COMBINATION_PRODUCTMenACWY-7B high dose vaccine
MenACWY-7B high dose vaccine is administered intramuscularly in the upper thigh region of the right leg.
COMBINATION_PRODUCTMenABCWY-1Gen vaccine
MenABCWY-1Gen vaccine is administered intramuscularly in the upper thigh region of the right leg.
COMBINATION_PRODUCTMenB vaccine
MenB vaccine is administered intramuscularly in the upper thigh region of the right leg.
COMBINATION_PRODUCTMenACWY-TT vaccine
MenACWY-TT vaccine is administered intramuscularly in the lower thigh region of the right leg.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Days to 89 Days
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Any Solicited Administration Site Events After the First Vaccination Administered on Day 1 | From Day 1 to Day 7 | The solicited administration site events include tenderness (administration site pain), erythema (redness), induration and swelling. Any solicited administration site events = occurrence of the event regardless of intensity grade. Data for solicited administration site events is presented for each intervention administered in each arm group. |
| Number of Participants Reporting Any Solicited Systemic Events After the First Vaccination Administered on Day 1 | From Day 1 to Day 7 | The solicited systemic events included diarrhoea, drowsiness (somnolence), fever (pyrexia), irritability/fussiness, loss of appetite, and vomiting. Fever is defined as temperature \>38.0°C/100.4°F. Any solicited systemic events = occurrence of the event regardless of intensity grade. |
| Number of Participants Reporting Any Solicited Administration Site Events After the Second Vaccination Administered on Day 61 | From Day 61 to Day 67 | — |
| Number of Participants Reporting Any Solicited Systemic Events After the Second Vaccination Administered on Day 61 | From Day 61 to Day 67 | — |
| Number of Participants Reporting Any Solicited Administration Site Events After the Third Vaccination Administered on Day 301 | From Day 301 to Day 307 | — |
| Number of Participants Reporting Any Solicited Systemic Events After the Third Vaccination Administered on Day 301 | From Day 301 to Day 307 | — |
| Number of Participants Reporting Any Unsolicited Adverse Events (AEs) After the First Vaccination Administered on Day 1 | From Day 1 to Day 30 | 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. Assessed unsolicited AEs include serious adverse events (SAEs), AEs leading to withdrawal, AEs of special interest (AESIs), and medically attended AEs (MAAEs). Any = occurrence of the event regardless of the intensity grade. |
| Number of Participants Reporting Any Unsolicited AEs After the Second Vaccination Administered on Day 61 | From Day 61 to Day 90 | — |
| Number of Participants Reporting Any Unsolicited AEs After the Third Vaccination Administered on Day 301 | From Day 301 to Day 330 | — |
| Number of Participants Reporting MAAEs, SAEs, AEs Leading to Withdrawal, and AESIs | From Day 1 to Day 481 | MAAEs 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. AEs leading to withdrawal are defined as AEs due which the participant is considered to have withdrawn from the study as no new study procedure has been performed or no new information has been collected for them since the date of withdrawal/last contact. |
| Percentage of Participants With Human Serum Bactericidal Assay (hSBA) Titers ≥ Lower Limit of Quantitation (LLOQ) for Each Serogroup B Indicator Strain at 1 Month After the Second Vaccination | At Day 91 (1 month after the second vaccination) | The immune response to the MenACWY-7B vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine was evaluated by measuring bactericidal activity using an hSBA against all serogroup B indicator strains fHbp, NadA, NHBA, PorA, fHbp V1.13, fHbp V2 and fHbp V3. |
| Percentage of Participants With hSBA Titers ≥ LLOQ for Each Serogroup B Indicator Strain at Pre-third Vaccination | At Day 301 (pre-third vaccination) | — |
| Percentage of Participants With hSBA Titers ≥ LLOQ for Each Serogroup B Indicator Strain at 1 Month After the Third Vaccination | At Day 331 (1 month after the third vaccination) | — |
| hSBA Geometric Mean Titers (GMTs) for Each Serogroup B Indicator Strain at 1 Month After the Second Vaccination | At Day 91 (1 month after the second vaccination) | The immune response to the MenACWY-7B vaccine (low and high dose), the MenABCWY-1Gen vaccine and the MenB vaccine against serogroup B indicator strains is determined using hSBA GMTs. |
| hSBA GMTs for Each Serogroup B Indicator Strain at Pre-third Vaccination | At Day 301 (pre-third vaccination) | — |
| hSBA GMTs for Each Serogroup B Indicator Strain at 1 Month After the Third Vaccination | At Day 331 (1 month after the third vaccination) | — |
| hSBA Geometric Mean Ratios (GMRs) for Each Serogroup B Indicator Strain | At Day 331 (1 month after the third vaccination) compared to Day 301 (pre-third vaccination) | The immune response to the MenACWY-7B 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. |
| Percentage of Participants With hSBA Titers ≥ LLOQ for Each A, C, W and Y Serogroup at 1 Month After the Second Vaccination | At Day 91 (1 month after the second vaccination) | The immune response to the MenACWY-7B 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. |
| Percentage of Participants With hSBA Titers ≥ LLOQ for Each A, C, W and Y Serogroup at Pre-third Vaccination | At Day 301 (pre-third vaccination) | — |
| Percentage of Participants With hSBA Titers ≥ LLOQ for Each A, C, W and Y Serogroup at 1 Month After the Third Vaccination | At Day 331 (1 month after the third vaccination) | — |
| hSBA GMTs for Each A, C, W and Y Serogroup at 1 Month After the Second Vaccination | At Day 91 (1 month after the second vaccination) | The immune response to the MenACWY-7B 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. |
| hSBA GMTs for Each A, C, W and Y Serogroup at Pre-third Vaccination | At Day 301 (pre-third vaccination) | — |
| hSBA GMTs for Each A, C, W and Y Serogroup at 1 Month After the Third Vaccination | At Day 331 (1 month after the third vaccination) | — |
| hSBA GMRs for Each A, C, W and Y Serogroup | At Day 331 (1 month after the third vaccination) compared to Day 301 (pre-third vaccination) | — |
Countries
Dominican Republic, Finland, Germany, Honduras, Poland, South Africa, Spain, United Kingdom
Participant flow
Pre-assignment details
A total of 726 participants were enrolled, of which 724 entered into the exposed set and started the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.2 DAYS STANDARD_DEVIATION 10.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 134 Participants |
| Race/Ethnicity, Customized Other | 64 Participants |
| Race/Ethnicity, Customized White | 520 Participants |
| Sex: Female, Male Female | 95 Participants |
| Sex: Female, Male Male | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 188 | 1 / 179 | 1 / 175 | 1 / 182 |
| other Total, other adverse events | 186 / 188 | 177 / 179 | 173 / 175 | 181 / 182 |
| serious Total, serious adverse events | 17 / 188 | 11 / 179 | 30 / 175 | 17 / 182 |
Outcome results
None listed