Poliomyelitis
Conditions
Brief summary
This will be a single center, age de-escalation, partly-blinded, randomized study. The trial will be performed with the participation of 100 healthy children age 1-5 years who have been vaccinated with inactivated polio vaccine (IPV) and/or oral polio vaccine (OPV) in their first year of life and of 648 healthy 6 week-old infants, who will be pre-vaccinated with bOPV-IPV before being randomized to study groups. The allocation of 18-22 week-old infants to groups will be performed in a randomized manner. Following completion and Data Safety Monitoring Board (DSMB) review of follow-up for general safety data (Serioius Adverse Events -SAEs-, Important Medical Events -IMEs- and severe adverse events -AEs), a DSMB recommendation to proceed will result in randomization of the final cohort of infants. Allocation of 1 to 5 year-old children to groups will be performed in a randomized manner. The DSMB will establish and continuously assess stopping rules for safety.
Interventions
BIOLOGICALnOPV2 (monovalent oral polio vaccine)
Cohort A: 150 IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 1 or 2; two 10‸6 CCID50 (50% cell culture infective dose) doses separated by 28 days. Cohort B: 972 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 10‸5 CCID50 dose of candidate 1 or 2.
Sponsors
Bill and Melinda Gates Foundation
Fidec Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Allocation of each subject to a given group will be described in a computer-generated randomization schedule. Based on this randomization code, the study vaccine will be packaged and labeled. Medication code numbers will be preprinted on the study vaccine labels and assigned as subjects qualify for the study and are randomly assigned to dosing schedule.
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 5 Years
Healthy volunteers
Yes
Inclusion criteria
1. For Cohort A children enrolled at 1 to 5 years of age who have previously been fully vaccinated according to MoH recommendations with OPV and/or IPV. 2. For Cohort B infants enrolled at 6 weeks of age (-1, + 2 weeks) with birth weight \>2,500 gm. To be eligible to continue into the experimental phase of the study infants must be vaccinated with 3 doses of bOPV and one dose of IPV prior to administration of the study vaccine at 18-22 weeks of age to take into account the visit windows for enrollment (age 6 weeks, -1 or + 2 weeks) and subsequent OPV vaccination windows (± 1 week). The last polio vaccine must have been administered at least 4 weeks prior to the first dose of study vaccine. Subjects in Cohort B who do not complete the three routine vaccination visits will be replaced in the study, and their parents/guardians will be encouraged to complete the primary vaccinations series. 3. Healthy children 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 to be in the study as established by the medical history and physical examination. 4. Written informed consent obtained from 1 or 2 parent(s) or legal guardian(s) as per country regulations.
Exclusion criteria
1. For all participants the presence of anyone under 10 years of age in the subject's household (living in the same house or apartment unit) who does not have complete age appropriate vaccination status with respect to poliovirus vaccines at the time of study vaccine administration. For household members younger than 18 months age appropriate vaccination is at least three (3) doses of IPV. For household members between 18 months and 10 years age appropriate vaccination is at least three (3) doses of IPV or tOPV plus one (1) booster dose of any antipolio vaccine. 2. For all participants having a member of the subject's household (living in the same house or apartment unit) who is under 6 months of age at the moment of study vaccine administration. 3. For all participants having a member of the subject's household (living in the same house or apartment unit) who has received OPV in the previous 3 months before study vaccine administration. 4. For Cohort A: receipt of polio vaccines within the 3 months prior to the administration of the study vaccine (number of previous polio vaccine doses to be documented). Any other vaccine 4 weeks before study entry. 5. For Cohort A: any participating children attending day care or pre-school during their participation in the study until one month after their last nOPV2 administration. 6. For Cohort B: any receipt of polio vaccines prior to administration of the study vaccine other than 3 doses of bOPV and 1 dose of IPV. 7. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus (HIV) infection in the potential participant or any member of the subject's household. 8. Family history of congenital or hereditary immunodeficiency. 9. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine). 10. Known allergy to any component of the study vaccines or to any antibiotics, that share molecular composition with the nOPV2 vaccines. 11. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections (of IPV). 12. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. 13. Acute severe febrile illness at 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.). 14. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 6 months | Number of subjects experiencing Serious Adverse Reactions (SAR), severe AR and IMR, i.e. SAEs, severe AEs (grade 3), or IMEs considered consistent with a causal association with study vaccines as of the informed consent signature date and throughout the study period in all groups. |
| Single Dose Seroprotection Rate | 2 months | Seroprotection rate of type 2 polio neutralizing antibodies at Day 28 following a single 105 or 106 CCID50 dose of nOPV2 candidates in all groups. Seroprotection rate is defined as the percentage of subjects with type 2-specific antibody titers ≥ 1:8 per group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seroprotection Rates Comparison | 2 months | Seroprotection rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study. Seroprotection rate is defined as the percentage of subjects with type 2-specific neutralizing antibody titers ≥ 1:8 per group. |
| Any Other SAEs, AEs and IMEs Incidence | 6 months | Number of participants experiencing any other SAE, any solicited AE, any unsolicited AEs and any IME as well as any clinical laboratory deviation considered consistent with causal association to study vaccine (primary objective) following one or two doses of either nOPV2 candidates. |
| Neurovirulence | 2 months | Potential for neurovirulence of virus isolated from a subset of stool samples of infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and following a single dose of both nOPV2 candidates at the 106 CCID50 dose level, as measured in an animal model, and compare this with a control sample (M2 study). For each of the children / infants receiving a 106 CCID50 dose of the 2018 cohorts as well as all participants in study M2, an exploratory endpoint sample (EES) of poliovirus shed in stools following the first dose was identified, if possible, with which to perform a modified neurovirulence test in a transgenic mouse model. Data from each sample tested was summarized by group per vaccine candidate. The proportion of mice paralyzed and the odds ratio of paralysis from the single-dose assay were the primary means of comparison of neurovirulence of shed virus between each candidate and the Sabin mOPV2 control samples. |
| Viral Shedding | 2 months | Level of viral shedding in stool at fixed time points following administration of one or two doses of both nOPV2 candidates at both 105 and 106 CCID50 dose levels in infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this shedding to a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study designed to serve as a control for the current study. This is determined by measuring the median number of days taken to get stool cultures negative for poliovirus presence (TTCN stands for median time to culture negative). Kaplan-Meier methods were used to describe the time to cessation of shedding for any shedding (PCR detection). |
| Seroconversion Rates Comparison | 2 months | Seroconversion rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study. Seroconversion is defined as a change from seronegative to seropositive, and in seropositive subjects, as an antibody titer increase of ≥ 4 fold over baseline (Day 0) titers corrected for maternal antibodies titers where applicable/age-appropriate. |
Countries
Panama
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stage I - Group A2H2 50 polio vaccine primed children aged 1 to \<5 years were to receive two 106 CCID50 doses of nOPV2 candidate 2, 2016, separated by 28 days (Group A2H2\[2016\]). | 50 |
| Stage II - A1H2 [2018] 50 IPV and/or OPV vaccinated participants aged 1 to 5 years administered with two 106 CCID50 doses of candidate 1 (2018) separated by 28 days. | 49 |
| Stage II - A2H2 [2018] 50 IPV and/or OPV vaccinated participants aged 1 to 5 years administered with two 106 CCID50 doses of candidate 2 (2018) separated by 28 days. | 51 |
| Stage I -- Group B2L1+L2[2016] 162 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 105 CCID50 dose of candidate 2 (2016).50 infants randomly selected from B2L1\[2016\] to receive a second 105 CCID50 dose of candidate 2 (2016), 28 days later. | 156 |
| Stage I - B2H1+H2[2016] 162 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 106 CCID50 dose of candidate 2 (2016).50 infants randomly selected from B2H1\[2016\] to receive a second 106 CCID50 dose of candidate 2 (2016), 28 days later. | 144 |
| Stage II - Group B1L1+L2[2018] 162 infants enrolled at 6 weeks of age (-7 to +14 days) administered with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 105 CCID50 dose of candidate 1 (2018).50 infants randomly selected to receive a second 105 CCID50 dose of candidate 1 (2018), 28 days later | 138 |
| Stage II - Group B1H1+H2[2018] 162 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 106 CCID50 dose of candidate 1.50 infants randomly selected to receive a second 106 CCID50 dose of candidate 1, 28 days later | 150 |
| Stage II - Group B2L1 +L2[2018] 162 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 105 CCID50 dose of candidate 2 \[2018\].50 infants randomly selected to receive a second 105 CCID50 dose of candidate 2 \[2018\], 28 days later. | 135 |
| Stage II - Group B2H1+H2[2018] 162 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 106 CCID50 dose of candidate 2 \[2018\].50 infants randomly selected to receive a second 106 CCID50 dose of candidate 2 \[2018\], 28 days later. | 151 |
| Total | 1,024 |
Baseline characteristics
| Characteristic | Total | Stage II - Group B2H1+H2[2018] | Stage II - Group B2L1 +L2[2018] | Stage II - Group B1H1+H2[2018] | Stage II - Group B1L1+L2[2018] | Stage I - B2H1+H2[2016] | Stage I -- Group B2L1+L2[2016] | Stage II - A2H2 [2018] | Stage II - A1H2 [2018] | Stage I - Group A2H2 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 1024 Participants | 151 Participants | 135 Participants | 150 Participants | 138 Participants | 144 Participants | 156 Participants | 51 Participants | 49 Participants | 50 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Central American Indian | 9 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed race | 981 Participants | 151 Participants | 132 Participants | 147 Participants | 135 Participants | 141 Participants | 151 Participants | 51 Participants | 49 Participants | 24 Participants |
| Race/Ethnicity, Customized Other | 26 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 26 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Panama | 1024 participants | 151 participants | 135 participants | 150 participants | 138 participants | 144 participants | 156 participants | 51 participants | 49 participants | 50 participants |
| Sex: Female, Male Female | 488 Participants | 73 Participants | 74 Participants | 71 Participants | 69 Participants | 65 Participants | 66 Participants | 29 Participants | 24 Participants | 17 Participants |
| Sex: Female, Male Male | 536 Participants | 78 Participants | 61 Participants | 79 Participants | 69 Participants | 79 Participants | 90 Participants | 22 Participants | 25 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 49 | 0 / 51 | 0 / 155 | 0 / 144 | 0 / 138 | 0 / 150 | 0 / 135 | 1 / 151 |
| other Total, other adverse events | 40 / 50 | 36 / 49 | 44 / 51 | 82 / 155 | 93 / 144 | 129 / 138 | 127 / 150 | 118 / 135 | 126 / 151 |
| serious Total, serious adverse events | 0 / 50 | 1 / 49 | 3 / 51 | 7 / 155 | 1 / 144 | 14 / 138 | 14 / 150 | 9 / 135 | 15 / 151 |
Outcome results
Primary
Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence
Number of subjects experiencing Serious Adverse Reactions (SAR), severe AR and IMR, i.e. SAEs, severe AEs (grade 3), or IMEs considered consistent with a causal association with study vaccines as of the informed consent signature date and throughout the study period in all groups.
Time frame: 6 months
Population: Safety parameters were tabulated and analyzed descriptively in the total vaccinated (TV) population, according to the actual vaccine received. TV population is defined as all subjects who received at least one dose of study vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage I - Group A2H2 | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 0 participants |
| Stage II - A1H2 [2018] | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 1 participants |
| Stage II - A2H2 [2018] | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 0 participants |
| Stage I -- Group B2L1+L2[2016] | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 5 participants |
| Stage I - B2H1+H2[2016] | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 6 participants |
| Stage II - Group B1L1+L2[2018] | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 1 participants |
| Stage II - Group B1H1+H2[2018] | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 1 participants |
| Stage II - Group B2L1 +L2[2018] | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 1 participants |
| Stage II - Group B2H1+H2[2018] | Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence | 1 participants |
Primary
Single Dose Seroprotection Rate
Seroprotection rate of type 2 polio neutralizing antibodies at Day 28 following a single 105 or 106 CCID50 dose of nOPV2 candidates in all groups. Seroprotection rate is defined as the percentage of subjects with type 2-specific antibody titers ≥ 1:8 per group.
Time frame: 2 months
Population: Per Protocol Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage I - Group A2H2 | Single Dose Seroprotection Rate | 45 Participants |
| Stage II - A1H2 [2018] | Single Dose Seroprotection Rate | 37 Participants |
| Stage II - A2H2 [2018] | Single Dose Seroprotection Rate | 47 Participants |
| Stage I -- Group B2L1+L2[2016] | Single Dose Seroprotection Rate | 125 Participants |
| Stage I - B2H1+H2[2016] | Single Dose Seroprotection Rate | 132 Participants |
| Stage II - Group B1L1+L2[2018] | Single Dose Seroprotection Rate | 122 Participants |
| Stage II - Group B1H1+H2[2018] | Single Dose Seroprotection Rate | 134 Participants |
| Stage II - Group B2L1 +L2[2018] | Single Dose Seroprotection Rate | 115 Participants |
| Stage II - Group B2H1+H2[2018] | Single Dose Seroprotection Rate | 138 Participants |
Secondary
Any Other SAEs, AEs and IMEs Incidence
Number of participants experiencing any other SAE, any solicited AE, any unsolicited AEs and any IME as well as any clinical laboratory deviation considered consistent with causal association to study vaccine (primary objective) following one or two doses of either nOPV2 candidates.
Time frame: 6 months
Population: Assessed in total vaccinated (TV) population, defined as all subjects who received at least one dose of study vaccine.Only secondary objectives included intent to compare the M5 data with the control sample which had received Sabin mOPV2 in M2 study (NCT02521974-historical control for M5).~Extent of exposure: in M5 Stage II, the second dose of study vaccine were received by 47 (94%) children in Group A1H2\[2018\] and 50 (98%) children in Group A2H2\[2018\].
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stage I - Group A2H2 | Any Other SAEs, AEs and IMEs Incidence | SAEs | 0 participants |
| Stage I - Group A2H2 | Any Other SAEs, AEs and IMEs Incidence | AEs | 32 participants |
| Stage I - Group A2H2 | Any Other SAEs, AEs and IMEs Incidence | IMEs | 1 participants |
| Stage II - A1H2 [2018] | Any Other SAEs, AEs and IMEs Incidence | SAEs | 1 participants |
| Stage II - A1H2 [2018] | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
| Stage II - A1H2 [2018] | Any Other SAEs, AEs and IMEs Incidence | AEs | 36 participants |
| Stage II - A2H2 [2018] | Any Other SAEs, AEs and IMEs Incidence | AEs | 44 participants |
| Stage II - A2H2 [2018] | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
| Stage II - A2H2 [2018] | Any Other SAEs, AEs and IMEs Incidence | SAEs | 2 participants |
| Stage I -- Group B2L1+L2[2016] | Any Other SAEs, AEs and IMEs Incidence | AEs | 30 participants |
| Stage I -- Group B2L1+L2[2016] | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
| Stage I -- Group B2L1+L2[2016] | Any Other SAEs, AEs and IMEs Incidence | SAEs | 2 participants |
| Stage I - B2H1+H2[2016] | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
| Stage I - B2H1+H2[2016] | Any Other SAEs, AEs and IMEs Incidence | SAEs | 0 participants |
| Stage I - B2H1+H2[2016] | Any Other SAEs, AEs and IMEs Incidence | AEs | 29 participants |
| Stage II - Group B1L1+L2[2018] | Any Other SAEs, AEs and IMEs Incidence | SAEs | 9 participants |
| Stage II - Group B1L1+L2[2018] | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
| Stage II - Group B1L1+L2[2018] | Any Other SAEs, AEs and IMEs Incidence | AEs | 34 participants |
| Stage II - Group B1H1+H2[2018] | Any Other SAEs, AEs and IMEs Incidence | AEs | 37 participants |
| Stage II - Group B1H1+H2[2018] | Any Other SAEs, AEs and IMEs Incidence | SAEs | 1 participants |
| Stage II - Group B1H1+H2[2018] | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
| Stage II - Group B2L1 +L2[2018] | Any Other SAEs, AEs and IMEs Incidence | AEs | 36 participants |
| Stage II - Group B2L1 +L2[2018] | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
| Stage II - Group B2L1 +L2[2018] | Any Other SAEs, AEs and IMEs Incidence | SAEs | 3 participants |
| Stage II - Group B2H1+H2[2018] | Any Other SAEs, AEs and IMEs Incidence | SAEs | 5 participants |
| Stage II - Group B2H1+H2[2018] | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
| Stage II - Group B2H1+H2[2018] | Any Other SAEs, AEs and IMEs Incidence | AEs | 33 participants |
| M2 Group 2+3 | Any Other SAEs, AEs and IMEs Incidence | IMEs | 1 participants |
| M2 Group 2+3 | Any Other SAEs, AEs and IMEs Incidence | SAEs | 0 participants |
| M2 Group 2+3 | Any Other SAEs, AEs and IMEs Incidence | AEs | 36 participants |
| M2 Children | Any Other SAEs, AEs and IMEs Incidence | SAEs | 1 participants |
| M2 Children | Any Other SAEs, AEs and IMEs Incidence | AEs | 28 participants |
| M2 Children | Any Other SAEs, AEs and IMEs Incidence | IMEs | 0 participants |
Secondary
Neurovirulence
Potential for neurovirulence of virus isolated from a subset of stool samples of infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and following a single dose of both nOPV2 candidates at the 106 CCID50 dose level, as measured in an animal model, and compare this with a control sample (M2 study). For each of the children / infants receiving a 106 CCID50 dose of the 2018 cohorts as well as all participants in study M2, an exploratory endpoint sample (EES) of poliovirus shed in stools following the first dose was identified, if possible, with which to perform a modified neurovirulence test in a transgenic mouse model. Data from each sample tested was summarized by group per vaccine candidate. The proportion of mice paralyzed and the odds ratio of paralysis from the single-dose assay were the primary means of comparison of neurovirulence of shed virus between each candidate and the Sabin mOPV2 control samples.
Time frame: 2 months
Population: Per the description under the Outcome Measure Description section, these groups do not match the participants arms distribution, as these results are related to the vaccine candidates behaviour in mice, not to the participating subjects.~Only secondary objectives included intent to compare the M5 data with the control sample of M2 study, which was designed to serve as a historical control for M5. For further details on results corresponding to M2 study, please refer to NCT02521974.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stage I - Group A2H2 | Neurovirulence | 90 percentage of neurovirulence |
| Stage II - A1H2 [2018] | Neurovirulence | 0 percentage of neurovirulence |
| Stage II - A2H2 [2018] | Neurovirulence | 30 percentage of neurovirulence |
Secondary
Seroconversion Rates Comparison
Seroconversion rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study. Seroconversion is defined as a change from seronegative to seropositive, and in seropositive subjects, as an antibody titer increase of ≥ 4 fold over baseline (Day 0) titers corrected for maternal antibodies titers where applicable/age-appropriate.
Time frame: 2 months
Population: Subset of subjects with baseline immunity (NAb titer) sufficiently low to enable observation of seroconversion (≤8.5 log2 i.e. ≤4-fold from assay ULOQ) at D56. Only secondary objectives included intent to compare the M5 data with the control sample of similarly aged infants and young children who had received Sabin mOPV2 in a M2 study, which was designed to serve as a historical control for M5.~For further details on results corresponding to M2 study, please refer to NCT02521974.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage I - Group A2H2 | Seroconversion Rates Comparison | 18 Participants |
| Stage II - A1H2 [2018] | Seroconversion Rates Comparison | 17 Participants |
| Stage II - A2H2 [2018] | Seroconversion Rates Comparison | 22 Participants |
| Stage I -- Group B2L1+L2[2016] | Seroconversion Rates Comparison | 40 Participants |
| Stage I - B2H1+H2[2016] | Seroconversion Rates Comparison | 43 Participants |
| Stage II - Group B1L1+L2[2018] | Seroconversion Rates Comparison | 44 Participants |
| Stage II - Group B1H1+H2[2018] | Seroconversion Rates Comparison | 47 Participants |
| Stage II - Group B2L1 +L2[2018] | Seroconversion Rates Comparison | 38 Participants |
| Stage II - Group B2H1+H2[2018] | Seroconversion Rates Comparison | 48 Participants |
| M2 Group 2+3 | Seroconversion Rates Comparison | 38 Participants |
| M2 Children | Seroconversion Rates Comparison | 6 Participants |
Secondary
Seroprotection Rates Comparison
Seroprotection rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study. Seroprotection rate is defined as the percentage of subjects with type 2-specific neutralizing antibody titers ≥ 1:8 per group.
Time frame: 2 months
Population: Subset of subjects with baseline immunity (NAb titer) sufficiently low to enable observation of seroconversion (≤8.5 log2 i.e. ≤4-fold from assay ULOQ) at D56. Only secondary objectives included intent to compare the M5 data with the control sample of similarly aged infants and young children who had received Sabin mOPV2 in a M2 study, which was designed to serve as a historical control for M5.~For further details on results corresponding to M2 study, please refer to NCT02521974.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage I - Group A2H2 | Seroprotection Rates Comparison | 44 Participants |
| Stage II - A1H2 [2018] | Seroprotection Rates Comparison | 39 Participants |
| Stage II - A2H2 [2018] | Seroprotection Rates Comparison | 46 Participants |
| Stage I -- Group B2L1+L2[2016] | Seroprotection Rates Comparison | 44 Participants |
| Stage I - B2H1+H2[2016] | Seroprotection Rates Comparison | 46 Participants |
| Stage II - Group B1L1+L2[2018] | Seroprotection Rates Comparison | 45 Participants |
| Stage II - Group B1H1+H2[2018] | Seroprotection Rates Comparison | 48 Participants |
| Stage II - Group B2L1 +L2[2018] | Seroprotection Rates Comparison | 43 Participants |
| Stage II - Group B2H1+H2[2018] | Seroprotection Rates Comparison | 48 Participants |
| M2 Group 2+3 | Seroprotection Rates Comparison | 39 Participants |
| M2 Children | Seroprotection Rates Comparison | 46 Participants |
Secondary
Viral Shedding
Level of viral shedding in stool at fixed time points following administration of one or two doses of both nOPV2 candidates at both 105 and 106 CCID50 dose levels in infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this shedding to a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study designed to serve as a control for the current study. This is determined by measuring the median number of days taken to get stool cultures negative for poliovirus presence (TTCN stands for median time to culture negative). Kaplan-Meier methods were used to describe the time to cessation of shedding for any shedding (PCR detection).
Time frame: 2 months
Population: Subset of subjects corresponding to 2018 Candidates cohorts. 2016 Candidate cohorts did not participate on this endpoint assessment.~Only secondary objectives included intent to compare the M5 data with the control sample of similarly aged infants and young children who had received Sabin mOPV2 in a M2 study, which was designed to serve as a historical control for M5.~For further details on results corresponding to M2 study, please refer to NCT02521974.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stage II - A1H2 [2018] | Viral Shedding | 5 days |
| Stage II - A2H2 [2018] | Viral Shedding | 3 days |
| Stage II - Group B1L1+L2[2018] | Viral Shedding | 6 days |
| Stage II - Group B1H1+H2[2018] | Viral Shedding | 6 days |
| Stage II - Group B2L1 +L2[2018] | Viral Shedding | 6 days |
| Stage II - Group B2H1+H2[2018] | Viral Shedding | 5 days |
| M2 Group 2+3 | Viral Shedding | 6 days |
| M2 Children | Viral Shedding | 6.5 days |