A Study to Evaluate the Safety and Immunogenicity of Novel Oral Polio Vaccine

• Sponsor: Fidec Corporation (Other)
• Overall Status: Completed
• CT.gov ID: NCT03554798
• Collaborator: Bill and Melinda Gates Foundation (Other)
• Enrollment: 1,025
• Locations: 2
• Arms: 2
• Actual Duration (Months): 14.5
• Patients Per Site: 512.5
• Patients Per Site Per Month: 35.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Poliomyelitis	Biological: nOPV2 (monovalent oral polio vaccine)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1025 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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.
• Primary Purpose: Prevention
• Official Title: A Phase 2 Study to Evaluate the Safety and Immunogenicity of Two Novel Oral Polio Type 2 (nOPV2) Vaccine Candidates in Healthy Children Aged 1 to 5 Years and in Healthy Bivalent Oral Polio Vaccine-inactivated Polio Vaccine (bOPV-IPV) Vaccinated Infants
• Actual Study Start Date: Dec 4, 2018
• Actual Primary Completion Date: Feb 19, 2020
• Actual Study Completion Date: Feb 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: nOPV2 Candidate 1 (monovalent oral poliovirus type1) Cohort A: IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 1. Cohort B: 6 weeks Infants vaccinated with 3 doses of bOPV and 1 dose of IPV, followed with 1 dose of candidate 1.	Biological: nOPV2 (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.
Experimental: nOPV2 Candidate 2 (monovalent oral poliovirus type2) Cohort A: IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 2. Cohort B: Infants vaccinated with 3 doses of bOPV and 1 dose of IPV, followed with 1 dose of candidate 2.	Biological: nOPV2 (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.

Outcome Measures

Primary Outcome Measures

1. Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence [6 months]

   Incidence of 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.

2. 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 Outcome Measures

1. SAEs, AEs and IMEs Incidence [6 months]

   Incidence, severity and causality of 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.

2. 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.

3. 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.

4. 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.

5. 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 of participants receiving the same vaccination schedule followed by a single dose of Sabin mOPV2 in a prior study (M2) designed to serve as a control for the current study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Weeks to 5 Years
• Sexes Eligible for Study: All
• Accepts 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.

1. 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.

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cevaxin Vaccination Center	David	Chiriquí	Panama
2	Cevaxin Vaccination Center	Panamá		Panama

Sponsors and Collaborators

• Fidec Corporation
• Bill and Melinda Gates Foundation

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 4, 2019

More Information

Publications

None provided.

• Responsible Party: Fidec Corporation
• ClinicalTrials.gov Identifier: NCT03554798
• Other Study ID Numbers: M5 ABMG
• First Posted: Jun 13, 2018
• Last Update Posted: Mar 23, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Poliomyelitis

Study Results

Participant Flow

Arm/Group Title	Stage I - Group A2H2	Stage II - A1H2 [2018]	Stage II - A2H2 [2018]	Stage I -- Group B2L1+L2[2016]	Stage I - B2H1+H2[2016]	Stage II - Group B1L1+L2[2018]	Stage II - Group B1H1+H2[2018]	Stage II - Group B2L1+L2 [2018]	Stage II - Group B2H1+H2[2018]
Arm/Group Description	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 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.	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.	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 randomly selected subjects from group B2L1 received a second 105 CCID50 dose of candidate 2 (2016), 28 days later.	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.	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).	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	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.	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.
Period Title: Overall Study
STARTED	50	50	51	156	144	138	150	135	151
COMPLETED	45	47	48	154	141	137	149	133	149
NOT COMPLETED	5	3	3	2	3	1	1	2	2

Baseline Characteristics

Arm/Group Title	Stage I - Group A2H2	Stage II - A1H2 [2018]	Stage II - A2H2 [2018]	Stage I -- Group B2L1+L2[2016]	Stage I - B2H1+H2[2016]	Stage II - Group B1L1+L2[2018]	Stage II - Group B1H1+H2[2018]	Stage II - Group B2L1 +L2[2018]	Stage II - Group B2H1+H2[2018]	Total
Arm/Group Description	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 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.	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.	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.	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.	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	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	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.	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.	Total of all reporting groups
Overall Participants	50	49	51	156	144	138	150	135	151	1024
Age (Count of Participants)
<=18 years	50 100%	49 100%	51 100%	156 100%	144 100%	138 100%	150 100%	135 100%	151 100%	1024 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	17 34%	24 49%	29 56.9%	66 42.3%	65 45.1%	69 50%	71 47.3%	74 54.8%	73 48.3%	488 47.7%
Male	33 66%	25 51%	22 43.1%	90 57.7%	79 54.9%	69 50%	79 52.7%	61 45.2%	78 51.7%	536 52.3%
Race/Ethnicity, Customized (Count of Participants)
Mixed race	24 48%	49 100%	51 100%	151 96.8%	141 97.9%	135 97.8%	147 98%	132 97.8%	151 100%	981 95.8%
Other	26 52%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	26 2.5%
Black or African American	0 0%	0 0%	0 0%	3 1.9%	0 0%	0 0%	1 0.7%	1 0.7%	0 0%	5 0.5%
Central American Indian	0 0%	0 0%	0 0%	1 0.6%	2 1.4%	3 2.2%	2 1.3%	1 0.7%	0 0%	9 0.9%
Hispanic	0 0%	0 0%	0 0%	1 0.6%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.1%
White	0 0%	0 0%	0 0%	0 0%	1 0.7%	0 0%	0 0%	1 0.7%	0 0%	2 0.2%
Region of Enrollment (participants) [Number]
Panama	50 100%	49 100%	51 100%	156 100%	144 100%	138 100%	150 100%	135 100%	151 100%	1024 100%

Outcome Measures

1. Primary Outcome

Title	Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence
Description	Incidence of 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stage I - Group A2H2	Stage II - A1H2 [2018]	Stage II - A2H2 [2018]	Stage I -- Group B2L1+L2[2016]	Stage I - B2H1+H2[2016]	Stage II - Group B1L1+L2[2018]	Stage II - Group B1H1+H2[2018]	Stage II - Group B2L1 +L2[2018]	Stage II - Group B2H1+H2[2018]
Arm/Group Description	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 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.	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.	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.	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.	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	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	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.	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.
Measure Participants	50	49	51	156	144	138	150	135	151
Count of Participants [Participants]	0 0%	1 2%	0 0%	5 3.2%	6 4.2%	1 0.7%	1 0.7%	1 0.7%	1 0.7%

2. Primary Outcome

Title	Single Dose Seroprotection Rate
Description	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

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Stage I - Group A2H2	Stage II - A1H2 [2018]	Stage II - A2H2 [2018]	Stage I -- Group B2L1+L2[2016]	Stage I - B2H1+H2[2016]	Stage II - Group B1L1+L2[2018]	Stage II - Group B1H1+H2[2018]	Stage II - Group B2L1+L2 [2018]	Stage II - Group B2H1+H2[2018]
Arm/Group Description	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 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.	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.	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 randomly selected subjects from group B2L1 received a second 105 CCID50 dose of candidate 2 (2016), 28 days later.	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.	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).	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	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.	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.
Measure Participants	45	37	47	145	136	131	143	127	146
Count of Participants [Participants]	45 90%	37 75.5%	47 92.2%	125 80.1%	132 91.7%	122 88.4%	134 89.3%	115 85.2%	138 91.4%

3. Secondary Outcome

Title	SAEs, AEs and IMEs Incidence
Description	Incidence, severity and causality of 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Seroconversion Rates Comparison
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Seroprotection Rates Comparison
Description	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.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Viral Shedding
Description	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.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Neurovirulence
Description	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 of participants receiving the same vaccination schedule followed by a single dose of Sabin mOPV2 in a prior study (M2) designed to serve as a control for the current study.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	6 months
Arm/Group Title	Stage I - Group A2H2		Stage II - A1H2 [2018]		Stage II - A2H2 [2018]		Stage I -- Group B2L1+L2[2016]		Stage I - B2H1+H2[2016]		Stage II - Group B1L1+L2[2018]		Stage II - Group B1H1+H2[2018]		Stage II - Group B2L1+L2 [2018]		Stage II - Group B2H1+H2[2018]
Arm/Group Description	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 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.		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.		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 randomly selected subjects from group B2L1 received a second 105 CCID50 dose of candidate 2 (2016), 28 days later.		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.		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).		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		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.		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.
All Cause Mortality
	Stage I - Group A2H2		Stage II - A1H2 [2018]		Stage II - A2H2 [2018]		Stage I -- Group B2L1+L2[2016]		Stage I - B2H1+H2[2016]		Stage II - Group B1L1+L2[2018]		Stage II - Group B1H1+H2[2018]		Stage II - Group B2L1+L2 [2018]		Stage II - Group B2H1+H2[2018]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		0/138 (0%)		0/150 (0%)		0/135 (0%)		1/151 (0.7%)
Serious Adverse Events
	Stage I - Group A2H2		Stage II - A1H2 [2018]		Stage II - A2H2 [2018]		Stage I -- Group B2L1+L2[2016]		Stage I - B2H1+H2[2016]		Stage II - Group B1L1+L2[2018]		Stage II - Group B1H1+H2[2018]		Stage II - Group B2L1+L2 [2018]		Stage II - Group B2H1+H2[2018]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		1/49 (2%)		3/51 (5.9%)		7/156 (4.5%)		1/144 (0.7%)		14/138 (10.1%)		14/150 (9.3%)		9/135 (6.7%)		15/151 (9.9%)
Cardiac disorders
Ventricular Septal Defect	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		1/138 (0.7%)		0/150 (0%)		0/135 (0%)		0/151 (0%)
Congenital, familial and genetic disorders
Congeniital Cortical Blindness	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		0/138 (0%)		0/150 (0%)		1/135 (0.7%)		0/151 (0%)
Ear and labyrinth disorders
Soft Tissue Abscess (preauricular)	0/50 (0%)		0/49 (0%)		1/51 (2%)		0/156 (0%)		0/144 (0%)		0/138 (0%)	0	0/150 (0%)	0	0/135 (0%)	0	0/151 (0%)	0
Gastrointestinal disorders
Acute Diarrheal Disease	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		1/138 (0.7%)		0/150 (0%)		0/135 (0%)		0/151 (0%)
Acute Gastroenteritis	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		0/138 (0%)		1/150 (0.7%)		2/135 (1.5%)		0/151 (0%)
General disorders
Urticaria	0/50 (0%)		0/49 (0%)		1/51 (2%)		0/156 (0%)		0/144 (0%)		0/138 (0%)		0/150 (0%)		0/135 (0%)		0/151 (0%)
Infections and infestations
Sepsis	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		0/138 (0%)		0/150 (0%)		0/135 (0%)		1/151 (0.7%)
Nervous system disorders
Tonic clonic seizure	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		1/138 (0.7%)	2	0/150 (0%)	2	0/135 (0%)	2	0/151 (0%)	2
Renal and urinary disorders
Urinary Tract Infection	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		0/138 (0%)		0/150 (0%)		1/135 (0.7%)		1/151 (0.7%)
Respiratory, thoracic and mediastinal disorders
Bronchiolitis	0/50 (0%)		1/49 (2%)		1/51 (2%)		2/156 (1.3%)		0/144 (0%)		9/138 (6.5%)		8/150 (5.3%)		2/135 (1.5%)		10/151 (6.6%)
Pneumonia	0/50 (0%)		0/49 (0%)		0/51 (0%)		4/156 (2.6%)		1/144 (0.7%)		4/138 (2.9%)	7	6/150 (4%)	7	4/135 (3%)	7	3/151 (2%)	7
Asthma	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		0/138 (0%)		0/150 (0%)		0/135 (0%)		1/151 (0.7%)
Skin and subcutaneous tissue disorders
Second degree burn	0/50 (0%)		0/49 (0%)		0/51 (0%)		1/156 (0.6%)		0/144 (0%)		0/138 (0%)		0/150 (0%)		0/135 (0%)		0/151 (0%)
Withlow left hand	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		1/138 (0.7%)		0/150 (0%)		0/135 (0%)		0/151 (0%)
Subcutaneous abscess	0/50 (0%)		0/49 (0%)		0/51 (0%)		0/156 (0%)		0/144 (0%)		0/138 (0%)		0/150 (0%)		0/135 (0%)		1/151 (0.7%)
Other (Not Including Serious) Adverse Events
	Stage I - Group A2H2		Stage II - A1H2 [2018]		Stage II - A2H2 [2018]		Stage I -- Group B2L1+L2[2016]		Stage I - B2H1+H2[2016]		Stage II - Group B1L1+L2[2018]		Stage II - Group B1H1+H2[2018]		Stage II - Group B2L1+L2 [2018]		Stage II - Group B2H1+H2[2018]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/50 (48%)		29/49 (59.2%)		26/51 (51%)		72/156 (46.2%)		53/144 (36.8%)		50/138 (36.2%)		63/150 (42%)		55/135 (40.7%)		64/151 (42.4%)
Gastrointestinal disorders
Vomiting	6/50 (12%)		5/49 (10.2%)		6/51 (11.8%)		20/156 (12.8%)		21/144 (14.6%)		19/138 (13.8%)		22/150 (14.7%)		20/135 (14.8%)		19/151 (12.6%)
General disorders
Irritability	2/50 (4%)		3/49 (6.1%)		5/51 (9.8%)		30/156 (19.2%)		18/144 (12.5%)		23/138 (16.7%)		27/150 (18%)		25/135 (18.5%)		25/151 (16.6%)
Abnormal crying	2/50 (4%)		7/49 (14.3%)		5/51 (9.8%)		35/156 (22.4%)		24/144 (16.7%)		26/138 (18.8%)		24/150 (16%)		21/135 (15.6%)		25/151 (16.6%)
Fever	6/50 (12%)		12/49 (24.5%)		15/51 (29.4%)		14/156 (9%)		12/144 (8.3%)		15/138 (10.9%)		12/150 (8%)		20/135 (14.8%)		18/151 (11.9%)
Loss of Appetite	16/50 (32%)		13/49 (26.5%)		13/51 (25.5%)		22/156 (14.1%)		13/144 (9%)		11/138 (8%)		15/150 (10%)		14/135 (10.4%)		19/151 (12.6%)
Drowsiness	2/50 (4%)		9/49 (18.4%)		5/51 (9.8%)		8/156 (5.1%)		9/144 (6.3%)		6/138 (4.3%)		11/150 (7.3%)		10/135 (7.4%)		15/151 (9.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.