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| ID | Type | Description | Link |
|---|---|---|---|
| INV-081593 | Other Grant/Funding Number | Gates Foundation |
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| Name | Class |
|---|---|
| Bill and Melinda Gates Foundation | OTHER |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| nOPV2 at birth | Experimental | Approximately 330 subjects to receive 1 dose of nOPV2 at birth followed by a regular IPV schedule at approx. 6, 10, 14 weeks of age and an nOPV2-002 challenge at approx. 18 weeks of age. |
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| nOPV2 at birth and Wk 14 of age | Experimental | Approximately 80 subjects to receive 2 doses of nOPV2 at birth and 14 wks of age plus a regular IPV schedule at approx. 6, 10, 14 weeks of age and an nOPV2-002 challenge at approx. 18 weeks of age. |
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| Placebo | Placebo Comparator | Approximately 330 subjects to receive 2 doses of placebo at birth and 14 wks of age plus a regular IPV schedule at approx. 6, 10, 14 weeks of age and an nOPV2-002 challenge at approx. 18 weeks of age |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| nOPV2 | Biological | nOPV2 will be administered at birth and Wk 14 of age depending on the study arm. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | From enrollment to the end of the study at Wk 22 of age. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From enrollment to the end of the study at 22 Wks of age. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ricardo Rüttimann, Dr. | Contact | +54 9 11 6118-8536 | rruttimann@fidec-online.org | |
| Gabriela Aguirre | Contact | +54 911 5964 7383 | gaguirre@fidec-online.org |
| Name | Affiliation | Role |
|---|---|---|
| Khaelqu Zaman, Dr. | International Centre for Diarrhoeal Disease Research, Bangladesh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| icddr,b - Matlab Health Research Centre | Chāndpur | Dhaka Division | Bangladesh |
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| ID | Term |
|---|---|
| D011051 | Poliomyelitis |
| ID | Term |
|---|---|
| D009187 | Myelitis |
| D002494 | Central Nervous System Infections |
| D007239 | Infections |
| D004769 | Enterovirus Infections |
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| 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. | 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. | 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. | 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. | 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. | 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. | From enrollment to the end of the study at Wk 22 of age. |
| D010850 |
| Picornaviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D000090862 | Neuroinflammatory Diseases |
| D009468 | Neuromuscular Diseases |