Poliomyelitis
Conditions
Brief summary
The study will compare the poliovirus type-2 pharyngeal mucosal excretion in the first week, and at 2 and 4 weeks following the administration of a challenge novel OPV2 (nOPV2) dose at 18 weeks of age in 2 parallel groups of infants
Detailed description
In the light of the switch from OPV to IPV and the continued presence of cVDPV2 in many countries, it is important to understand and quantify the impact of IPV on pharyngeal mucosal immunity, to inform whether and to what extent the mucosal and humoral immune response following IPV could reduce transmission and spread. This study will assess the effect of vaccination with IPV in parallel with poliovirus type-2 naïve infants (infants having received bOPV) on the pharyngeal and fecal shedding and the induction of immunity following type-2 poliovirus challenge. This understanding would provide critical information on the potential use of IPV in specific settings to interrupt transmission / reduce spread. The results from this study may potentially have important consequences on public health policy in countries which use IPV for infant priming, as they will help to show the extent to which a type-2 mucosal immunity gap remains following a primary series of IPV.
Interventions
BIOLOGICALnOPV2
Vaccination
Sponsors
Fidec Corporation
Bill and Melinda Gates Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Weeks to 8 Weeks
Healthy volunteers
Yes
Inclusion criteria
1. Infants aged 6 to 8 weeks with birth weight \>2,500 g. 2. Healthy infants without obvious medical conditions like immunodeficiency diseases, severe congenital malformations, severe neurological diseases or any other disease that require high doses of corticosteroids or immunotherapies that preclude the subject from participating in the study as established by the medical history and physical examination. 3. Written informed consent obtained from both parents or legal guardian(s) as per country regulations.
Exclusion criteria
1. Infants who have received previous vaccination against poliomyelitis. 2. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus infection in the potential participant or any member of the subject's household. 3. Family history of congenital or hereditary immunodeficiency. 4. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine). 5. Known allergy to any component of the study vaccines or to any antibiotics that share molecular composition with a component of the study vaccines. 6. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections (of IPV) 7. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. 8. Acute severe febrile illness on the day of vaccination deemed by the Investigator to be a contraindication for vaccination (the child can be included at a later time if within age window and all inclusion criteria are met.). 9. Subject who, in the opinion of the Investigator, is unlikely to comply with the protocol or is inappropriate to be included in the study for the safety or the benefit-risk ratio of the subject. 10. Infants from multiple births or born prematurely (\< 37 weeks of gestation).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Shedding Detectable Levels of Poliovirus Type-2 by RT PCR. | 1 month | To compare the presence of poliovirus type-2 in pharyngeal samples detected by reverse-transcription polymerase chain reaction (RT PCR) in the first week, and at D14 and D28 in both groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharyngeal Neutralizing Antibodies (NAbs) to Poliovirus Type-2. | 1 month | To assess and compare the pharyngeal NAbs poliovirus type-2 activity on D0, D14 and D28 in both groups. |
| Seroprotection Rate to Poliovirus Type-2 on D0, D28 and D56 in Both Groups. | 2 months | To assess the humoral immunogenicity to poliovirus type-2 at D0, 4 and 8 weeks following administration of a challenge dose of nOPV2 in both groups. Seroprotection is defined as neutralizing type-2 poliovirus antibody specific titers ≥1:8. |
| Number of Participants That Experienced Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | 5 months | To assess the number of subjects experiencing SAEs and IMEs following administration of IPV, bOPV and nOPV2 throughout the whole study period. |
| Pharyngeal Poliovirus Type-2-specific Immunoglobulin A (IgA) Concentrations | 1 month | To asses and compare the pharyngeal mucosal immunoglobulin class-specific immune response to poliovirus type-2 at Day 0, 2 and 4 weeks following administration of a challenge dose of nOPV2 in both groups.This is measured in geometric mean concentrations (GMCs) in nasal samples on D0, D14 and D28 in both groups. |
Countries
Bangladesh
Participant flow
Pre-assignment details
500 participants started the study, while 501 signed the informed consent. One of them resulted in Screening Failure.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 500 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 500 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Bangladesh | 250 participants |
| Sex: Female, Male Female | 254 Participants |
| Sex: Female, Male Male | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 250 | 0 / 250 |
| other Total, other adverse events | 0 / 250 | 0 / 250 |
| serious Total, serious adverse events | 5 / 250 | 2 / 250 |
Outcome results
None listed