Poliomyelitis
Conditions
Brief summary
A Phase 4 study to evaluate the safety and immunogenicity of monovalent oral polio vaccine type 2 in healthy IPV-vaccinated children aged 1 to 5 years in Lithuania.
Detailed description
Sabin 2 will be withdrawn from routine use globally from April 2016 as per the SAGE recommendations at the time of writing this protocol. After this cessation of OPV2, stockpiles of mOPV2 will be maintained for potential use if necessary in response to a future outbreak. However, there is a risk of cVDPV2 from Sabin 2 in settings of low population immunity. Research is ongoing to develop vaccines that are genetically more stable than the currently available Sabin 2-containing OPVs. To generate data on immunogenicity, safety, and genetic stability on the Sabin 2 vaccine (mOPV2) and as a future comparator for new polio vaccine research after the global switch from tOPV to bOPV, this study with mOPV2 is performed to evaluate safety, immunogenicity (humoral and intestinal) and genetic stability endpoints of mOPV2 in children aged 1 to 5 years for better understanding of the stockpile use of this vaccine, and any potential new polio vaccine with a type 2 component in the future.
Interventions
BIOLOGICALSabin mOPV2
Polio Sabin™ Mono Two (oral) is a licensed, monovalent, live attenuated poliomyelitis virus vaccine of the Sabin strain Type 2 (P 712, Ch, 2ab), propagated in MRC5 human diploid cells. Each two-drop dose (0.1 mL) contains not less than 105.0 CCID50 of Type 2. Magnesium chloride is used as a stabilizer. Polio Sabin™ Mono Two (Oral) contains trace amounts of neomycin sulphate and polymyxin B sulphate. One dose of vaccine (0.1 mL) is contained in two drops which are delivered from the polyethylene dropper supplied with vaccine.
Sponsors
Bill and Melinda Gates Foundation
Fidec Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 5 Years
Healthy volunteers
Yes
Inclusion criteria
1. 1 to 5 years of age, previously vaccinated with three or four doses of IPV. 2. Healthy without obvious medical conditions that preclude entry of the subject into the study as established by the medical history and physical examination. 3. Written informed consent obtained from 1 or 2 parent(s) or legal guardian(s) as per country regulations.
Exclusion criteria
1. Previous vaccination against poliovirus outside the national immunization schedule. 2. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus (HIV) infection. 3. Family history of congenital or hereditary immunodeficiency. 4. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine). 5. Known allergy to any component of the study vaccines or to any antibiotics. 6. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. 7. 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 Severe AEs | 3 months | Incidence of SAEs and severe AEs grade 3 considered consistent with a causal association to study vaccine throughout the study period in children 1 to 5 years. |
| Seroprotection Rate of Type 2 Polio Neutralizing Antibodies. | 1 month | Seroprotection rate at type 2 polio neutralizing antibodies measured at D28 after the first dose of mOPV2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seroprotection Rate for Type 2 Polio Neutralizing Antibodies. | 3 months | Seroprotection rate for type 2 polio neutralizing antibodies measured at D 28 after the secon dose of mOPV2. |
| Incidence of Any Serious Adverse Events (SAEs), Any Solicited AEs, Any Unsolicited AEs, and Any Important Medical Events (IMEs). | 3 months | Incidence, severity and relationship) of any serious adverse events (SAEs), any solicited AEs, any unsolicited AEs, and any Important Medical Events (IMEs) with the exception of severe related AEs. (primary objective), as well as any laboratory deviations of one or two doses of SABIN mOPV2 in healthy IPV-vaccinated children aged 1 to 5 years. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 IPV-vaccinated children receiving 1 dose of SABIN mOPV2. | 50 |
| Group 2 IPV-vaccinated children receiving 2 doses of SABIN mOPV2. | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 3 |
Baseline characteristics
| Characteristic | Total | Group 2 | Group 1 |
|---|---|---|---|
| Age, Categorical <=18 years | 100 Participants | 50 Participants | 50 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 100 Participants | 50 Participants | 50 Participants |
| Region of Enrollment Lithuania | 100 participants | 50 participants | 50 participants |
| Sex: Female, Male Female | 45 Participants | 19 Participants | 26 Participants |
| Sex: Female, Male Male | 55 Participants | 31 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 6 / 50 | 12 / 50 |
| serious Total, serious adverse events | 0 / 50 | 1 / 50 |
Outcome results
Primary
SAEs and Severe AEs
Incidence of SAEs and severe AEs grade 3 considered consistent with a causal association to study vaccine throughout the study period in children 1 to 5 years.
Time frame: 3 months
Population: All participants who received at least one dose of vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | SAEs and Severe AEs | 0 Participants |
| Group 2 | SAEs and Severe AEs | 0 Participants |
p-value: 0.05Clopper-Pearson
Primary
Seroprotection Rate of Type 2 Polio Neutralizing Antibodies.
Seroprotection rate at type 2 polio neutralizing antibodies measured at D28 after the first dose of mOPV2.
Time frame: 1 month
Population: All participants who received two doses of vaccines.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Seroprotection Rate of Type 2 Polio Neutralizing Antibodies. | 50 Participants |
| Group 2 | Seroprotection Rate of Type 2 Polio Neutralizing Antibodies. | 47 Participants |
p-value: 0.025Clopper-Pearson
Secondary
Incidence of Any Serious Adverse Events (SAEs), Any Solicited AEs, Any Unsolicited AEs, and Any Important Medical Events (IMEs).
Incidence, severity and relationship) of any serious adverse events (SAEs), any solicited AEs, any unsolicited AEs, and any Important Medical Events (IMEs) with the exception of severe related AEs. (primary objective), as well as any laboratory deviations of one or two doses of SABIN mOPV2 in healthy IPV-vaccinated children aged 1 to 5 years.
Time frame: 3 months
Population: All subjects receiving at least one dose of vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Incidence of Any Serious Adverse Events (SAEs), Any Solicited AEs, Any Unsolicited AEs, and Any Important Medical Events (IMEs). | 6 Participants |
| Group 2 | Incidence of Any Serious Adverse Events (SAEs), Any Solicited AEs, Any Unsolicited AEs, and Any Important Medical Events (IMEs). | 9 Participants |
p-value: 0.05Clopper-Pearson
Secondary
Seroprotection Rate for Type 2 Polio Neutralizing Antibodies.
Seroprotection rate for type 2 polio neutralizing antibodies measured at D 28 after the secon dose of mOPV2.
Time frame: 3 months
Population: All subjects receiving two doses of vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Seroprotection Rate for Type 2 Polio Neutralizing Antibodies. | 47 Participants |
p-value: 0.025Clopper-Pearson