The study will compare the transmissible levels of poliovirus type-2 detected in stool samples collected at the time of the nOPV2 challenge and subsequent timepoints in 3 groups of newborns receiving an nOPV2 dose at birth and primed with 3 doses of IPV (6 - 10 - 14 weeks of age).
To meet the urgent public health need regarding cVDPV2 outbreaks, a novel type 2 OPV (nOPV2) vaccine was developed using attenuated serotype 2 polioviruses derived from a modified Sabin 2 infectious cDNA clone generated by modifying the Sabin-2 ribonucleic acid (RNA) sequence to improve genetic stability and make the strains less prone to reversion to virulence. Clinical trials in adults, children, and infants demonstrated that nOPV2 vaccine is safe, well tolerated, and immunogenic. These include a phase 2 study of vaccine-naïve neonates in Bangladesh who received either two doses of nOPV2 or two doses of placebo at birth and 4 weeks of age concluded that the vaccine was well tolerated and immunogenic, as 90% of the infants seroconverted at 2 weeks post second dose. Overall 99% of infants had protective levels of neutralizing antibody at this time in contrast to the seroprotection rate of 56% in the placebo group. Although immunogenic, the effect of nOPV2 on virus transmission is still unclear. This phase 3 study aims to compare the transmissible levels of poliovirus type-2 detected in stool samples collected at the time of the nOPV2 challenge (pre-challenge) and subsequent timepoints in 3 groups of newborns receiving an nOPV2 dose at birth and primed with 3 doses of IPV (6 - 10 - 14 weeks of age).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
740
nOPV2 will be administered at birth and Wk 14 of age depending on the study arm.
icddr,b - Matlab Health Research Centre
Chāndpur, Dhaka Division, Bangladesh
Stool viral load
To assess the presence or absence of "transmissible" levels of virus in stool, with presence defined as a log10 CCID50 per gram of ≥4.3 at Visit 7 (Day 126; day of nOPV2 challenge dose administration), Visit 8 (Day 130), Visit 9 (Day 133), Visit 10 (Day 140), and Visit 11 (Day 154) in all groups.
Time frame: From enrollment to the end of the study at Wk 22 of age.
PV Type 2 neutralizing activity in stool samples
To assess poliovirus type-2-specific neutralizing activity and total concentrations and poliovirus type-2-specific IgA/IgG mean fluorescence intensities (MFI) in stool samples at Visit 7 (Day 126), Visit 8 (Day 130), Visit 9 (Day 133), Visit 10 (Day 140), and Visit 11 (Day 154) in all groups.
Time frame: From enrollment to the end of the study at 22 Wks of age.
PV Type 2 seroprotection rate
To assess the seroprotection (SP) rate to poliovirus type-2 on Day 42 (Visit 4) and Week 18 (Visit 7). SP rate is defined as the percentage of subjects with type 2-specific antibody titers ≥ 1:8 in all groups.
Time frame: From enrollment till 18 Wks of age
PV Type 2 seroconversion rate
To assess the seroconversion (SC) rate of poliovirus type-2 neutralizing antibodies on Week 18 (Visit 7) of age in all groups.
Time frame: From enrollment till Wk 18 of age.
PV Type 2 neutralization titers
To assess the geometric mean and median poliovirus type-2-specific neutralization titers on Week 6 (Visit 4) and Week 18 (Visit 7) of age in all groups.
Time frame: From enrollment till Wk 18 of age
SAEs and IMEs
Incidence of SAEs and IMEs by severity and by causal association from the date of informed consent throughout the study period in all groups.
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Time frame: From enrollment to the end of the study at Wk 22 of age
Solicited AEs
Incidence of mild, moderate and severe solicited AEs (fever, vomiting, abnormal crying, drowsiness, loss of appetite, diarrhea and irritability) for 7 days after each dose of study vaccine/placebo in all groups.
Time frame: From enrollment to Wk 18 of age
Viral shedding
To assess the positivity rate in the poliovirus type-specific RT-PCR assay at Visit 7 (Day 126; day of nOPV2 challenge dose administration), Visit 8 (Day 130), Visit 9 (Day 133), Visit 10 (Day 140), and Visit 11 (Day 154) in all groups.
Time frame: From enrollment to the end of the study at Wk 22 of age.