Poliomyelitis
Conditions
Brief summary
Study to determine immunogenicity and safety following administration of 2 doses of novel oral poliovirus vaccine type 2 (nOPV2) given at different intervals of 1 week or 2 weeks or the standard 4-week interval in infants
Detailed description
This will be a multicenter, randomized, controlled, open-label, parallel-group Phase III study in healthy infants aged 6 to 8 weeks who have never been vaccinated against poliomyelitis. Approximately 900 infants will be included in the study and randomized with a 1:1:1 ratio to the following treatment groups: * Group A: approximately 300 subjects to receive 2 doses of nOPV2 administered 1 week apart, at Day 0 and Day 7; * Group B: approximately 300 subjects to receive 2 doses of nOPV2 administered 2 weeks apart, at Day 0 and Day 14; * Group C (control group): approximately 300 subjects to receive 2 doses of nOPV2 administered 4 weeks apart, at Day 0 and Day 28. A total of 4 on-site visits are planned. Approximately 7 days after each administration of study vaccine, a phone call or on-site visit will be performed to monitor subjects' safety and review with the subject's parent(s)/guardian(s) any solicited AEs reported in the electronic diary card. All subjects will have a safety follow-up phone call 6 months after the last dose of study vaccine.
Interventions
BIOLOGICALnOPV2
Novel Oral Poliomyelitis Type 2 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
6 Weeks to 8 Weeks
Healthy volunteers
Yes
Inclusion criteria
1. Infants aged 6 to 8 weeks with birth weight \> 2,500 g. 2. Healthy infants 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 from participating in 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. Infants who have received previous vaccination against poliomyelitis. 2. Infants with anyone under 5 years of age in their household (living in the same house or apartment unit) who does not have the complete age appropriate vaccination status with respect to poliovirus vaccines at the time of study vaccine administration according to the Dominican Republic National Immunization Program (NIP). 3. Infants having a member of their household (living in the same house or apartment unit) who is under 6 months of age at the moment of study vaccine administration. 4. Infants having a member of their household (living in the same house or apartment unit) who has received oral poliomyelitis vaccine (OPV) in the previous 3 months before study vaccine administration. 5. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus infection in the potential participant or any member of the subject's household. 6. Family history of congenital or hereditary immunodeficiency. 7. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine). 8. Known allergy to any component of the study vaccine or to any antibiotics that share molecular composition with the nOPV2 vaccine. 9. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. 10. Acute severe febrile illness on the 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.). 11. 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. 12. Infants from multiple births or born prematurely (\< 37 weeks of gestation)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion Rate at 1, 2 & 4 Weeks Interval | Up to max 8 weeks | Cumulative seroconversion rate of type 2 polio neutralizing antibodies 28 days following administration of 2 doses of nOPV2 in 1-week, 2-week and 4-weeks interval to infants 6 to 8 weeks of age |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutralizing Antibodies at 1, 2 & 4 Week Interval | Up to max 8 weeks | Geometric mean titers of type 2 polio neutralizing antibodies at Day 0 and 28 days after the second dose of nOPV2 when administered 1, 2 & 4 weeks apart. |
| Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | 6 months | Number of participants experiencing SAEs and IMEs from the date of informed consent throughout the study period in all groups by severity and by causal association. |
| Solicited Adverse Events (AEs) | Up to max 5 weeks | Number of participants experiencing 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 in all groups. |
| Unsolicited Adverse Events (AEs) | Up to max 8 weeks | Number of participants experiencing mild, moderate, and severe solicited AEs (fever, vomiting, abnormal crying, drowsiness, loss of appetite, diarrhea, and irritability) for 28 days after each dose of study vaccine in all groups. |
Countries
Dominican Republic
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Administration of 2 doses of nOPV2, 1 week apart | 302 |
| Group B Administration of 2 doses of nOPV2, 2 weeks apart | 300 |
| Group C Administration of 2 doses of nOPV2, 4 weeks apart | 303 |
| Total | 905 |
Baseline characteristics
| Characteristic | Group A | Group B | Group C | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 302 Participants | 300 Participants | 303 Participants | 905 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Mixed Race | 301 Participants | 299 Participants | 301 Participants | 901 Participants |
| Region of Enrollment Dominican Republic | 302 participants | 300 participants | 303 participants | 905 participants |
| Sex: Female, Male Female | 134 Participants | 138 Participants | 146 Participants | 418 Participants |
| Sex: Female, Male Male | 168 Participants | 162 Participants | 157 Participants | 487 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 298 | 0 / 304 | 1 / 303 |
| other Total, other adverse events | 217 / 298 | 247 / 304 | 238 / 303 |
| serious Total, serious adverse events | 8 / 298 | 7 / 304 | 9 / 303 |
Outcome results
Primary
Seroconversion Rate at 1, 2 & 4 Weeks Interval
Cumulative seroconversion rate of type 2 polio neutralizing antibodies 28 days following administration of 2 doses of nOPV2 in 1-week, 2-week and 4-weeks interval to infants 6 to 8 weeks of age
Time frame: Up to max 8 weeks
Population: Per Protocol population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Seroconversion Rate at 1, 2 & 4 Weeks Interval | 253 Participants |
| Group B | Seroconversion Rate at 1, 2 & 4 Weeks Interval | 269 Participants |
| Group C | Seroconversion Rate at 1, 2 & 4 Weeks Interval | 277 Participants |
Comparison: This study was designed to demonstrate the non-inferiority of Group A (1-week interval nOPV2 administration) and Group B (2-weeks interval nOPV2 administration) versus Group C (standard 4-week interval).p-value: 0.05Miettinen-Nurminen
Comparison: This study was designed to demonstrate the non-inferiority of Group A (1-week interval nOPV2 administration) and Group B (2-weeks interval nOPV2 administration) versus Group C (standard 4-week interval).p-value: 0.05Miettinen-Nurminen
Secondary
Neutralizing Antibodies at 1, 2 & 4 Week Interval
Geometric mean titers of type 2 polio neutralizing antibodies at Day 0 and 28 days after the second dose of nOPV2 when administered 1, 2 & 4 weeks apart.
Time frame: Up to max 8 weeks
Population: Per Protocol Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group A | Neutralizing Antibodies at 1, 2 & 4 Week Interval | Day 0 | 10.7 titers |
| Group A | Neutralizing Antibodies at 1, 2 & 4 Week Interval | 28 days after 2nd dose | 1232.3 titers |
| Group B | Neutralizing Antibodies at 1, 2 & 4 Week Interval | Day 0 | 11.5 titers |
| Group B | Neutralizing Antibodies at 1, 2 & 4 Week Interval | 28 days after 2nd dose | 1726.3 titers |
| Group C | Neutralizing Antibodies at 1, 2 & 4 Week Interval | Day 0 | 10.2 titers |
| Group C | Neutralizing Antibodies at 1, 2 & 4 Week Interval | 28 days after 2nd dose | 2327.6 titers |
Comparison: This study was designed to demonstrate the non-inferiority of Group A (1-week interval nOPV2 administration) and Group B (2-weeks interval nOPV2 administration) versus Group C (standard 4-week interval).p-value: 0.05Miettinen-Nurminen
Comparison: This study was designed to demonstrate the non-inferiority of Group A (1-week interval nOPV2 administration) and Group B (2-weeks interval nOPV2 administration) versus Group C (standard 4-week interval).p-value: 0.05Miettinen-Nurminen
Secondary
Serious Adverse Events (SAEs) and Important Medical Events (IMEs)
Number of participants experiencing SAEs and IMEs from the date of informed consent throughout the study period in all groups by severity and by causal association.
Time frame: 6 months
Population: Total Vaccinated Population. Please note that for the safety analysis, subjects were classified according to the actual administration interval received per the Statistical Analysis Plan. Thus, 4 patients randomized into Group A were assigned to Group B for safety analysis tables.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Hospitalization | 8 Participants |
| Group A | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Death | 0 Participants |
| Group A | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Birth defect | 1 Participants |
| Group B | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Hospitalization | 7 Participants |
| Group B | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Death | 0 Participants |
| Group B | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Birth defect | 1 Participants |
| Group C | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Death | 1 Participants |
| Group C | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Birth defect | 0 Participants |
| Group C | Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Hospitalization | 9 Participants |
Secondary
Solicited Adverse Events (AEs)
Number of participants experiencing 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 in all groups.
Time frame: Up to max 5 weeks
Population: Total Vaccinated Population. Please note that for the safety analysis, subjects were classified according to the actual administration interval received per the Statistical Analysis Plan. Thus, 4 patients randomized into Group A were assigned to Group B for safety analysis tables.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A | Solicited Adverse Events (AEs) | Drowsiness | 25 Participants |
| Group A | Solicited Adverse Events (AEs) | Vomiting | 45 Participants |
| Group A | Solicited Adverse Events (AEs) | Irritability | 31 Participants |
| Group A | Solicited Adverse Events (AEs) | Fever | 134 Participants |
| Group A | Solicited Adverse Events (AEs) | Diarrhea | 44 Participants |
| Group A | Solicited Adverse Events (AEs) | Abnormal crying | 84 Participants |
| Group A | Solicited Adverse Events (AEs) | Loss of Apetite | 36 Participants |
| Group B | Solicited Adverse Events (AEs) | Fever | 147 Participants |
| Group B | Solicited Adverse Events (AEs) | Abnormal crying | 90 Participants |
| Group B | Solicited Adverse Events (AEs) | Diarrhea | 50 Participants |
| Group B | Solicited Adverse Events (AEs) | Drowsiness | 38 Participants |
| Group B | Solicited Adverse Events (AEs) | Irritability | 45 Participants |
| Group B | Solicited Adverse Events (AEs) | Loss of Apetite | 49 Participants |
| Group B | Solicited Adverse Events (AEs) | Vomiting | 75 Participants |
| Group C | Solicited Adverse Events (AEs) | Irritability | 41 Participants |
| Group C | Solicited Adverse Events (AEs) | Diarrhea | 40 Participants |
| Group C | Solicited Adverse Events (AEs) | Vomiting | 62 Participants |
| Group C | Solicited Adverse Events (AEs) | Loss of Apetite | 38 Participants |
| Group C | Solicited Adverse Events (AEs) | Fever | 139 Participants |
| Group C | Solicited Adverse Events (AEs) | Drowsiness | 36 Participants |
| Group C | Solicited Adverse Events (AEs) | Abnormal crying | 83 Participants |
Secondary
Unsolicited Adverse Events (AEs)
Number of participants experiencing mild, moderate, and severe solicited AEs (fever, vomiting, abnormal crying, drowsiness, loss of appetite, diarrhea, and irritability) for 28 days after each dose of study vaccine in all groups.
Time frame: Up to max 8 weeks
Population: Total Vaccinated Population. Please note that for the safety analysis, subjects were classified according to the actual administration interval received per the Statistical Analysis Plan (SAP). Thus, 4 patients randomized into Group A were assigned to Group B for safety analysis tables.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A | Unsolicited Adverse Events (AEs) | Skin disorders | 0 Participants |
| Group A | Unsolicited Adverse Events (AEs) | Congenital disorders | 0 Participants |
| Group A | Unsolicited Adverse Events (AEs) | Nervous system disorders | 0 Participants |
| Group A | Unsolicited Adverse Events (AEs) | General disorders | 1 Participants |
| Group A | Unsolicited Adverse Events (AEs) | Respiratory disorders | 13 Participants |
| Group A | Unsolicited Adverse Events (AEs) | Infections | 9 Participants |
| Group A | Unsolicited Adverse Events (AEs) | Gastrointestinal disorders | 3 Participants |
| Group A | Unsolicited Adverse Events (AEs) | Musculoskeletal and connective tissue disorders | 0 Participants |
| Group B | Unsolicited Adverse Events (AEs) | Musculoskeletal and connective tissue disorders | 0 Participants |
| Group B | Unsolicited Adverse Events (AEs) | Skin disorders | 2 Participants |
| Group B | Unsolicited Adverse Events (AEs) | Respiratory disorders | 10 Participants |
| Group B | Unsolicited Adverse Events (AEs) | Congenital disorders | 1 Participants |
| Group B | Unsolicited Adverse Events (AEs) | Gastrointestinal disorders | 13 Participants |
| Group B | Unsolicited Adverse Events (AEs) | Infections | 10 Participants |
| Group B | Unsolicited Adverse Events (AEs) | General disorders | 8 Participants |
| Group B | Unsolicited Adverse Events (AEs) | Nervous system disorders | 1 Participants |
| Group C | Unsolicited Adverse Events (AEs) | General disorders | 6 Participants |
| Group C | Unsolicited Adverse Events (AEs) | Gastrointestinal disorders | 9 Participants |
| Group C | Unsolicited Adverse Events (AEs) | Respiratory disorders | 11 Participants |
| Group C | Unsolicited Adverse Events (AEs) | Musculoskeletal and connective tissue disorders | 3 Participants |
| Group C | Unsolicited Adverse Events (AEs) | Skin disorders | 1 Participants |
| Group C | Unsolicited Adverse Events (AEs) | Congenital disorders | 1 Participants |
| Group C | Unsolicited Adverse Events (AEs) | Nervous system disorders | 0 Participants |
| Group C | Unsolicited Adverse Events (AEs) | Infections | 14 Participants |