Poliomyelitis
Conditions
Brief summary
The purpose of this study is to assess the safety (serious adverse events \[SAEs\]), and severe adverse events \[AEs\] (grade 3 according to CTCAE 4.03) after one dose of SABIN tOPV in 1-5 year-old children and three doses of SABIN tOPV in 6 week-old infants, and immunogenicity (seroprotection rates for all 3 serotypes) 28 days after three doses of SABIN tOPV in vaccine-naïve infants.
Detailed description
This will be a single center, open study in children (aged 1 to 5 years) and vaccine-naïve infants, as follows: 50 OPV-vaccinated children aged 1 to 5 years to receive 1 dose of tOPV (Group 1); 104 vaccine-naïve infants to receive 3 doses of tOPV administered 28 days apart (Group 2)
Interventions
BIOLOGICALOral Polio Vaccine
Opvero™ (oral) is a trivalent, live attenuated poliomyelitis virus vaccine containing at least 6.0 log 50% cell culture infective dose (CCID50) of LS c2ab strain of live attenuated polio virus type 1, 5.0 log CCID50 of P712, Ch, 2ab strain of live attenuated polio virus type 2, 5.8 log CCID50 Leon I2aIb strain of polio virus type 3. Excipients: human albumin, HEPES buffer solution, magnesium chloride solution (containing polysorbate 80 and phenol red), hydrochloric acid or sodium hydroxide for pH adjustment. The vaccine is presented as a suspension for oral administration. One dose of vaccine (0.1 ml) is contained in two drops which are delivered from the dropper supplied with the multidose container.
Sponsors
Bill and Melinda Gates Foundation
Fidec Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Weeks to 5 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age: Group 1- Children aged 1-5 years, previously vaccinated with ≥ 3 doses of OPV. Group 2- Infants aged 6 weeks (-7 to +14 days) with no previous polio vaccinations. 2. Healthy without obvious medical conditions that preclude the subject to be in the study as established by the medical history and physical examination. 3. Written informed consent obtained from 1 or 2 parents or legal guardians as per Dominican Republic regulations.
Exclusion criteria
1. Previous Vaccinations: Group 1: Previous vaccination against poliovirus outside of the national immunization schedule and any vaccine in the previous 4 weeks. Group 2: Any vaccination against poliovirus 2. Group 2: Infants with birth weight (BW) \< 2,500 gm. 3. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus (HIV) infection. 4. Family history of congenital or hereditary immunodeficiency. 5. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine). 6. Known allergy to any component of the study vaccines or to any antibiotics. 7. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections. 8. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. 9. 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 in/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SAEs and AEs G3 | 6 months | Number of subjects experiencing SAEs and severe AEs grade 3 considered consistent with a causal association to study vaccine 28 days after three doses of SABIN tOPV in vaccine-naïve infants in Dominican Republic. |
| Seroprotection Rate | 3 months | Seroprotection rate of type-specific polio neutralizing antibodies at Day 84, 28 days after the third dose of SABIN tOPV in infants (Group 2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutralizing Antibodies 1 | 3 months | Median titers of type-specific neutralizing antibodies at Days 0 and 28 in children aged 1-5 years (Group 1), and at Days 0 and 84 in infants (Group 2). |
| Seroconversion Rate | 3 months | Seroconversion rate of type-specific neutralizing antibodies at Day 28 for Group 1, and at Day 84 for Group 2. |
| Neutralizing Antibodies 2 | 3 months | Geometric mean antibody titers (GMT) of type-specific neutralizing antibodies at Days 0 and 28 in children aged 1-5 years (Group 1), and at Days 0 and 84 in infants (Group 2). |
| Seroprotection Rates | 4 weeks | Seroprotection rates of type-specific neutralizing antibodies at Days 0 and 28 in Group 1 and at Day 0 in Group 2. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 tOPV-vaccinated healthy children aged 1 to 5 years to receive 1 dose of SABIN | 50 |
| Group 2 Vaccine-naïve infants to receive 3 doses of SABIN tOPV administered 28 days apart | 104 |
| Total | 154 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 50 Participants | 104 Participants | 154 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 50 Participants | 104 Participants | 154 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Dominican Republic | 50 Participants | 104 Participants | 154 Participants |
| Sex/Gender, Customized Female | 23 Participants | 56 Participants | 79 Participants |
| Sex/Gender, Customized Male | 27 Participants | 48 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 104 |
| other Total, other adverse events | 8 / 50 | 52 / 104 |
| serious Total, serious adverse events | 0 / 50 | 0 / 104 |
Outcome results
Primary
SAEs and AEs G3
Number of subjects experiencing SAEs and severe AEs grade 3 considered consistent with a causal association to study vaccine 28 days after three doses of SABIN tOPV in vaccine-naïve infants in Dominican Republic.
Time frame: 6 months
Population: Total vaccinated population (TVP)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group1 | SAEs and AEs G3 | 0 Participants |
| Group 2 | SAEs and AEs G3 | 0 Participants |
Primary
Seroprotection Rate
Seroprotection rate of type-specific polio neutralizing antibodies at Day 84, 28 days after the third dose of SABIN tOPV in infants (Group 2).
Time frame: 3 months
Population: Per Protocol Population (PP)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group1 | Seroprotection Rate | Serotype 1 | 93.3 percentage of participants |
| Group1 | Seroprotection Rate | Serotype 2 | 100 percentage of participants |
| Group1 | Seroprotection Rate | Serotype 3 | 96.2 percentage of participants |
Secondary
Neutralizing Antibodies 1
Median titers of type-specific neutralizing antibodies at Days 0 and 28 in children aged 1-5 years (Group 1), and at Days 0 and 84 in infants (Group 2).
Time frame: 3 months
Population: Per Protocol Population (PP)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group1 | Neutralizing Antibodies 1 | Serotype 1 | 10.50 log^2 |
| Group1 | Neutralizing Antibodies 1 | Serotype 2 | 9.83 log^2 |
| Group1 | Neutralizing Antibodies 1 | Serotype 3 | 8.50 log^2 |
| Group 2 | Neutralizing Antibodies 1 | Serotype 1 | 10.50 log^2 |
| Group 2 | Neutralizing Antibodies 1 | Serotype 2 | 10.17 log^2 |
| Group 2 | Neutralizing Antibodies 1 | Serotype 3 | 8.83 log^2 |
Secondary
Neutralizing Antibodies 2
Geometric mean antibody titers (GMT) of type-specific neutralizing antibodies at Days 0 and 28 in children aged 1-5 years (Group 1), and at Days 0 and 84 in infants (Group 2).
Time frame: 3 months
Population: Per Protocol Population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Group1 | Neutralizing Antibodies 2 | Serotype 1 | 445.5 GMTs |
| Group1 | Neutralizing Antibodies 2 | Serotype 2 | 681.2 GMTs |
| Group1 | Neutralizing Antibodies 2 | Serotype 3 | 306.3 GMTs |
| Group 2 | Neutralizing Antibodies 2 | Serotype 1 | 650.8 GMTs |
| Group 2 | Neutralizing Antibodies 2 | Serotype 2 | 712.2 GMTs |
| Group 2 | Neutralizing Antibodies 2 | Serotype 3 | 352.1 GMTs |
Secondary
Seroconversion Rate
Seroconversion rate of type-specific neutralizing antibodies at Day 28 for Group 1, and at Day 84 for Group 2.
Time frame: 3 months
Population: Per protocol population (PP)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group1 | Seroconversion Rate | Serotype 1 | 32.7 percentage of participants |
| Group1 | Seroconversion Rate | Serotype 2 | 36.7 percentage of participants |
| Group1 | Seroconversion Rate | Serotype 3 | 46.9 percentage of participants |
| Group 2 | Seroconversion Rate | Serotype 1 | 88.5 percentage of participants |
| Group 2 | Seroconversion Rate | Serotype 2 | 98.1 percentage of participants |
| Group 2 | Seroconversion Rate | Serotype 3 | 96.2 percentage of participants |
Secondary
Seroprotection Rates
Seroprotection rates of type-specific neutralizing antibodies at Days 0 and 28 in Group 1 and at Day 0 in Group 2.
Time frame: 4 weeks
Population: Per Protocol Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group1 | Seroprotection Rates | Serotype 1 | 93.0 percentage of participants |
| Group1 | Seroprotection Rates | Serotype 2 | 100 percentage of participants |
| Group1 | Seroprotection Rates | Serotype 3 | 98 percentage of participants |
| Group 2 | Seroprotection Rates | Serotype 1 | 60.6 percentage of participants |
| Group 2 | Seroprotection Rates | Serotype 2 | 60.6 percentage of participants |
| Group 2 | Seroprotection Rates | Serotype 3 | 26 percentage of participants |