Trial Outcomes & Findings for Phase 1 Novel Live Attenuated Serotype 2 Oral Polio Vaccine Study in Inactivated Polio Vaccine (IPV) Primed Adults (NCT NCT03430349)
NCT ID: NCT03430349
Last Updated: 2021-02-04
Results Overview
Serious adverse events are medical events that resulted in death, were life-threatening, required admission to hospital, or resulted in notable incapacity of the individual. Adverse events were also graded from mild to severe; Severe adverse events are medical events that prevent normal everyday activities or fever \> 39°C; this category does not include serious adverse events. Serious adverse events and severe adverse events include both solicited and unsolicited events. Solicited events comprised signs and symptoms that were reported by the participant using a predefined checklist in a diary card, or a fever, as determined by the participant's measurement of their body temperature, for up to 7 days after vaccination. Unsolicited events comprised other signs and symptoms recorded through the end of the study. Adverse events were assessed by the investigator for causality as unrelated, unlikely, possibly, or probably related to the vaccination.
COMPLETED
PHASE1
30 participants
From Day 0 up to 42 days
2021-02-04
Participant Flow
Volunteers were recruited via local advertising and confined in a purpose-built containment facility at the University of Antwerp Hospital (Antwerp, Belgium) to minimize the risk of environmental release of the vaccine virus. Volunteers included healthy adults previously vaccinated with inactivated polio vaccine (IPV).
Participants were enrolled sequentially into one of two groups, and received a single dose of one of two novel oral polio vaccine type 2 (nOPV2) candidates. Participants were monitored for adverse events, immune responses, and fecal shedding of the vaccine virus for 28 days. If if shedding continued beyond 28 days participants were asked to further collect stool samples daily on an ambulatory basis until end of shedding.
Participant milestones
| Measure |
Novel OPV2 Candidate 1
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ 50% cell culture infectious dose units \[CCID50\]).
|
Novel OPV2 Candidate 2
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
Received nOPV Vaccination
|
15
|
15
|
|
Overall Study
COMPLETED
|
15
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase 1 Novel Live Attenuated Serotype 2 Oral Polio Vaccine Study in Inactivated Polio Vaccine (IPV) Primed Adults
Baseline characteristics by cohort
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ 50% cell culture infectious dose units \[CCID50\]).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.1 years
STANDARD_DEVIATION 7.72 • n=5 Participants
|
33.5 years
STANDARD_DEVIATION 10.93 • n=7 Participants
|
32.3 years
STANDARD_DEVIATION 9.38 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
14 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Day 0 up to 42 daysPopulation: All randomized participants who received a dose of study vaccine.
Serious adverse events are medical events that resulted in death, were life-threatening, required admission to hospital, or resulted in notable incapacity of the individual. Adverse events were also graded from mild to severe; Severe adverse events are medical events that prevent normal everyday activities or fever \> 39°C; this category does not include serious adverse events. Serious adverse events and severe adverse events include both solicited and unsolicited events. Solicited events comprised signs and symptoms that were reported by the participant using a predefined checklist in a diary card, or a fever, as determined by the participant's measurement of their body temperature, for up to 7 days after vaccination. Unsolicited events comprised other signs and symptoms recorded through the end of the study. Adverse events were assessed by the investigator for causality as unrelated, unlikely, possibly, or probably related to the vaccination.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study
≥1 serious adverse event
|
0 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study
≥1 severe adverse event (AE)
|
6 Participants
|
9 Participants
|
|
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study
≥1 severe AE probably related to vaccine
|
0 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study
≥1 severe AE possibly related to vaccine
|
6 Participants
|
9 Participants
|
|
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study
≥1 severe AE unlikely related to vaccine
|
0 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events and Severe Adverse Events Throughout the Study
≥1 severe AE unrelated
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28Population: All randomized participants who received study vaccine with available stool samples at each time point.
Participants provided stool samples for assessment of viral shedding, defined as the presence of type 2-specific poliovirus ribonucleic acid (RNA) in stools. Samples were analyzed by the US Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) for the presence of type-2 poliovirus genome using a Sabin multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of total nucleic acid extracted from stool suspensions (50% weight to volume in cell culture medium).
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Percentage of Participants With Viral Shedding
Day 0
|
0.0 percentage of participants
Interval 0.0 to 25.9
|
0.0 percentage of participants
Interval 0.0 to 29.9
|
|
Percentage of Participants With Viral Shedding
Day 2
|
50.0 percentage of participants
Interval 26.8 to 73.2
|
53.8 percentage of participants
Interval 29.1 to 76.8
|
|
Percentage of Participants With Viral Shedding
Day 3
|
100 percentage of participants
Interval 79.6 to 100.0
|
71.4 percentage of participants
Interval 45.4 to 88.3
|
|
Percentage of Participants With Viral Shedding
Day 4
|
92.9 percentage of participants
Interval 68.5 to 98.7
|
42.9 percentage of participants
Interval 21.4 to 67.4
|
|
Percentage of Participants With Viral Shedding
Day 5
|
92.9 percentage of participants
Interval 68.5 to 98.7
|
83.3 percentage of participants
Interval 55.2 to 95.3
|
|
Percentage of Participants With Viral Shedding
Day 6
|
100 percentage of participants
Interval 78.5 to 100.0
|
64.3 percentage of participants
Interval 38.8 to 83.7
|
|
Percentage of Participants With Viral Shedding
Day 7
|
100 percentage of participants
Interval 78.5 to 100.0
|
72.7 percentage of participants
Interval 43.4 to 90.3
|
|
Percentage of Participants With Viral Shedding
Day 14
|
76.9 percentage of participants
Interval 49.7 to 91.8
|
23.1 percentage of participants
Interval 8.2 to 50.3
|
|
Percentage of Participants With Viral Shedding
Day 21
|
64.3 percentage of participants
Interval 38.8 to 83.7
|
23.1 percentage of participants
Interval 8.2 to 50.3
|
|
Percentage of Participants With Viral Shedding
Day 28
|
45.5 percentage of participants
Interval 21.3 to 72.0
|
37.5 percentage of participants
Interval 13.7 to 69.4
|
|
Percentage of Participants With Viral Shedding
Day 1
|
38.5 percentage of participants
Interval 17.7 to 64.5
|
7.1 percentage of participants
Interval 1.3 to 31.5
|
PRIMARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28Population: All randomized participants who received study vaccine and with type 2 poliovirus-positive stool samples at each time point.
In stool samples that were positive for type-2 poliovirus detected by RT-PCR, infectious virus was measured as 50% cell culture infective dose (CCID₅₀) per gram of stool by use of a modification of the World Health Organization (WHO) cell sensitivity assay.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 1
|
3.22 log₁₀ (CCID₅₀/g)
Interval 2.88 to 4.09
|
4.41 log₁₀ (CCID₅₀/g)
Interval 4.41 to 4.41
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 2
|
3.66 log₁₀ (CCID₅₀/g)
Interval 3.53 to 3.81
|
3.44 log₁₀ (CCID₅₀/g)
Interval 3.0 to 4.03
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 3
|
4.50 log₁₀ (CCID₅₀/g)
Interval 3.69 to 4.69
|
3.52 log₁₀ (CCID₅₀/g)
Interval 3.0 to 4.02
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 4
|
4.16 log₁₀ (CCID₅₀/g)
Interval 3.91 to 4.41
|
3.27 log₁₀ (CCID₅₀/g)
Interval 2.94 to 4.21
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 5
|
3.84 log₁₀ (CCID₅₀/g)
Interval 3.41 to 4.38
|
3.08 log₁₀ (CCID₅₀/g)
Interval 2.91 to 3.2
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 6
|
3.91 log₁₀ (CCID₅₀/g)
Interval 3.71 to 4.24
|
3.53 log₁₀ (CCID₅₀/g)
Interval 2.88 to 3.78
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 7
|
4.05 log₁₀ (CCID₅₀/g)
Interval 3.84 to 4.53
|
3.44 log₁₀ (CCID₅₀/g)
Interval 2.91 to 3.81
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 14
|
3.06 log₁₀ (CCID₅₀/g)
Interval 2.88 to 3.63
|
2.88 log₁₀ (CCID₅₀/g)
Interval 2.78 to 3.97
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 21
|
3.00 log₁₀ (CCID₅₀/g)
Interval 2.84 to 3.38
|
3.19 log₁₀ (CCID₅₀/g)
Interval 3.06 to 3.94
|
|
Cell Culture Infective Dose of Shed Virus in Virus-positive Stool Samples
Day 28
|
2.91 log₁₀ (CCID₅₀/g)
Interval 2.75 to 3.69
|
3.19 log₁₀ (CCID₅₀/g)
Interval 3.03 to 4.09
|
PRIMARY outcome
Timeframe: Stool samples were collected from the day of vaccination to Day 28 or until shedding cessation; up to 89 days (novel OPV2 candidate 1) and 48 days (novel OPV candidate 2).Population: All randomized participants who received a dose of study vaccine with at least one type 2 poliovirus-positive stool sample.
The time to cessation of shedding was defined as the time interval between administration of vaccine and the date of the first sample negative for type 2 poliovirus shedding (assessed by RT-PCR) after which the following two consecutive samples were also negative. Time to cessation of viral shedding was assessed using Kaplan-Meier methods; participants were right-censored if they had not met this endpoint with the last stool sample collected.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Time to Shedding Cessation
|
23 days
Interval 15.0 to 36.0
|
12 days
Interval 1.0 to 23.0
|
PRIMARY outcome
Timeframe: Days 7, 14, 21, and 28Population: All randomized participants who received a dose of study vaccine. Missing values (from missing samples on specific study days) were replaced with values from the days before or after or the average of these two values, as necessary.
A combined index of the prevalence, duration, and quantity of viral shedding in all participants. The viral shedding index was calculated for each participant as the mean of log₁₀(CCID₅₀/g) of samples collected 7, 14, 21, and 28 days after vaccine administration, with the lower limit of quantitation (2.75 log₁₀) as an observed value, and all titers in stool samples with negative shedding results (real-time RT-PCR-negative values) contributing 0 to the mean.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Shedding Index
|
2.84 log₁₀(CCID₅₀/g)
Interval 1.77 to 3.46
|
0.95 log₁₀(CCID₅₀/g)
Interval 0.7 to 1.57
|
SECONDARY outcome
Timeframe: Day 0 to Day 7Population: All randomized participants who received a dose of study vaccine.
Adverse events were solicited from the participants by the medical team during the 7 days after vaccination. Solicited events comprised signs and symptoms that were reported with a predefined checklist in a diary card, including headache, fatigue, myalgia, arthralgia, paresthesia, anesthesia, paralysis, nausea, vomiting, diarrhea and abdominal pain, or fever defined as a temperature of 37.5°C or higher. Adverse events were graded as mild (easily tolerated), moderate (sufficiently discomforting to interfere with normal everyday activities), or severe (preventing normal everyday activities, or temperatures higher than 39.0°C). Adverse events were assessed by the investigator for causality as unrelated, unlikely, possibly, or probably related to the vaccination.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Number of Participants With Solicited Adverse Events
Any solicited adverse event
|
13 Participants
|
9 Participants
|
|
Number of Participants With Solicited Adverse Events
Mild
|
8 Participants
|
8 Participants
|
|
Number of Participants With Solicited Adverse Events
Moderate
|
5 Participants
|
1 Participants
|
|
Number of Participants With Solicited Adverse Events
Severe
|
0 Participants
|
0 Participants
|
|
Number of Participants With Solicited Adverse Events
Unrelated/Unlikely related to vaccination
|
11 Participants
|
2 Participants
|
|
Number of Participants With Solicited Adverse Events
Probably/Possibly related to vaccination
|
4 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: From Day 0 up to 42 daysPopulation: All randomized participants who received a dose of study vaccine.
Unsolicited events comprised other signs and symptoms that participants reported through the end of the study. Each unsolicited AE was rated on a 3-point scale of increasing intensity: * Grade 1: Mild; an AE that was easily tolerated by the subject, causing minimal discomfort and not interfering with everyday activities. * Grade 2: Moderate; an AE that was sufficiently discomforting to interfere with normal everyday activities. * Grade 3: Severe; an AE that prevented normal everyday activities. Each adverse event was assessed by the investigator for causality as unrelated, unlikely, possibly, or probably related to the vaccination.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Number of Participants With Unsolicited Adverse Events
Any unsolicited adverse event
|
15 Participants
|
15 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Mild
|
3 Participants
|
3 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Moderate
|
6 Participants
|
3 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Severe
|
6 Participants
|
9 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Unrelated/Unlikely related to vaccination
|
14 Participants
|
9 Participants
|
|
Number of Participants With Unsolicited Adverse Events
Probably/Possibly related to vaccination
|
10 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Screening, Day 7, Day 14, and Day 28Population: All randomized participants who received study vaccine
Clinical laboratory test values were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (toxicity grades) or in accordance with the normal ranges of the clinical laboratory (below, within, or above normal range) for parameters for which no toxicity grades were defined. Clinical chemistry assessments included total bilirubin, glucose, blood urea nitrogen (BUN), creatinine, calcium, inorganic phosphate, potassium, sodium, alanine aminotransferase, aspartate aminotransferase, and C-reactive protein (CRP). Hematology assessments included hemoglobin, hematocrit, red blood cells, and white blood cells with differential.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Clinical Chemistry at Screening
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Clinical Chemistry at Day 7
|
4 Participants
|
7 Participants
|
|
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Clinical Chemistry at Day 14
|
3 Participants
|
5 Participants
|
|
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Clinical Chemistry at Day 28
|
6 Participants
|
1 Participants
|
|
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Hematology at Screening
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Hematology at Day 7
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Hematology at Day 14
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Relevant Deviations From Normal Laboratory Evaluations
Hematology at Day 28
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 0 and Day 28Population: All randomized participants who received study vaccine and had no exclusion criterion or major protocol deviations.
Neutralizing antibodies against poliovirus type 2 were determined using the WHO standard microneutralization assay (WHO EPI GEN 93.9).
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Anti-Poliovirus Type-2 Neutralizing Antibody Titers
Day 0
|
56.89 log₂ titer
Interval 36.0 to 181.0
|
36.00 log₂ titer
Interval 22.63 to 90.51
|
|
Anti-Poliovirus Type-2 Neutralizing Antibody Titers
Day 28
|
1152.1 log₂ titer
Interval 576.0 to 1448.2
|
724.1 log₂ titer
Interval 362.0 to 1152.1
|
SECONDARY outcome
Timeframe: Day 0 and Day 28Population: All randomized participants who received study vaccine and had no exclusion criterion or major protocol deviations.
Seroprotection rate was defined as the percentage of participants in each group with anti-type 2-specific poliovirus neutralizing antibodies titers ≥ 1:8.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Seroprotection Rate
Day 0 (pre-vaccination)
|
100 percentage of participants
Interval 78.2 to 100.0
|
93.3 percentage of participants
Interval 68.1 to 99.8
|
|
Seroprotection Rate
Day 28
|
100 percentage of participants
Interval 78.2 to 100.0
|
100 percentage of participants
Interval 78.2 to 100.0
|
SECONDARY outcome
Timeframe: Day 28Population: Randomized participants who received study vaccine with no exclusion criterion or major protocol deviations. Five participants (2 in the nOPV2-Candidate 1 group, 3 in the nOPV2-Candidate 2 group) with pre-vaccination type 2- neutralizing antibody titers too close to the upper limit of quantitation to measure a 4-fold increase are excluded.
Seroconversion rate is defined as the percentage of participants in each group with a change from seronegative to seropositive (poliovirus type-2-specific neutralizing antibody titers ≥ 1:8) or, in participants seropositive at Baseline, an increase in neutralizing antibody titer of at least four-fold from Baseline.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=12 Participants
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=13 Participants
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Seroconversion Rate
|
83.3 percentage of participants
Interval 51.6 to 97.9
|
84.6 percentage of participants
Interval 54.6 to 98.1
|
SECONDARY outcome
Timeframe: Samples tested were the last post-vaccination sample per participant suitable for analysis; samples used in the analysis ranged from Day 2 to Day 56Population: Participants with stool samples evaluable by the neurovirulence test; in the nOPV2-Candidate 2 group only six participants shed sufficient virus at any time point to attempt virus amplification, and amplification did not work for four of these.
Neurovirulence of shed virus was measured using a modified WHO poliovirus receptor transgenic mouse neurovirulence test (mTgmNVT). The last stool sample provided by each participant that had adequate concentrations of virus for the neurovirulence assay (≥ 4 log₁₀\[CCID₅₀/g\]) was used in the test. For each stool specimen thirty Tg-PVR21 mice were administered intraspinal inoculations of 4 log₁₀(CCID₅₀) amplified virus. After 14 days the inoculated mice were assessed as either paralyzed or non-paralyzed. For each participant/sample, the percentage of paralyzed mice was calculated. Overall percent paralysis is the average percentage of paralyzed mice over all participants in each group.
Outcome measures
| Measure |
Novel OPV2 Candidate 1
n=446 innoculated mice
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=58 innoculated mice
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
|---|---|---|
|
Neurovirulence Assessed by the Average Percent Paralysis in Inoculated Mice
|
1.6 percent paralysis
Interval 0.0 to 10.0
|
6.9 percent paralysis
Interval 0.0 to 14.3
|
Adverse Events
Novel OPV2 Candidate 1
Novel OPV2 Candidate 2
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Novel OPV2 Candidate 1
n=15 participants at risk
Participants received one vaccination with novel OPV2 candidate 1 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
|
Novel OPV2 Candidate 2
n=15 participants at risk
Participants received one vaccination with novel OPV2 candidate 2 on study Day 0, administered orally as six drops (0.3 mL total; approximately 10⁶ CCID50).
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|---|---|---|
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Investigations
Blood creatine phosphokinase increased
|
60.0%
9/15 • From Day 0 up to 42 days
|
73.3%
11/15 • From Day 0 up to 42 days
|
|
Investigations
Aspartate aminotransferase increased
|
46.7%
7/15 • From Day 0 up to 42 days
|
60.0%
9/15 • From Day 0 up to 42 days
|
|
Investigations
Alanine aminotransferase increased
|
40.0%
6/15 • From Day 0 up to 42 days
|
53.3%
8/15 • From Day 0 up to 42 days
|
|
Investigations
Bilirubin conjugated increased
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Investigations
Blood bilirubin increased
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Investigations
Gamma-glutamyltransferase increased
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Investigations
White blood cell count decreased
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
1/15 • From Day 0 up to 42 days
|
33.3%
5/15 • From Day 0 up to 42 days
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
3/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
1/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/15 • From Day 0 up to 42 days
|
13.3%
2/15 • From Day 0 up to 42 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15 • From Day 0 up to 42 days
|
13.3%
2/15 • From Day 0 up to 42 days
|
|
Gastrointestinal disorders
Abdominal distension
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Gastrointestinal disorders
Aphthous ulcer
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.0%
3/15 • From Day 0 up to 42 days
|
13.3%
2/15 • From Day 0 up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/15 • From Day 0 up to 42 days
|
13.3%
2/15 • From Day 0 up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
6.7%
1/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Tendon pain
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Nervous system disorders
Headache
|
20.0%
3/15 • From Day 0 up to 42 days
|
33.3%
5/15 • From Day 0 up to 42 days
|
|
Nervous system disorders
Syncope
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Infections and infestations
Viral upper respiratory tract infection
|
13.3%
2/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Infections and infestations
Enterobiasis
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Infections and infestations
Paronychia
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Infections and infestations
Pharyngitis
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Infections and infestations
Root canal infection
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Infections and infestations
Tinea pedis
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
13.3%
2/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Injury, poisoning and procedural complications
Thermal burn
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
13.3%
2/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Respiratory, thoracic and mediastinal disorders
Larynx irritation
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Psychiatric disorders
Insomnia
|
13.3%
2/15 • From Day 0 up to 42 days
|
13.3%
2/15 • From Day 0 up to 42 days
|
|
Psychiatric disorders
Nervousness
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.3%
2/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Skin and subcutaneous tissue disorders
Acne cystic
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
General disorders
Fatigue
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
General disorders
Malaise
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
General disorders
Pyrexia
|
0.00%
0/15 • From Day 0 up to 42 days
|
6.7%
1/15 • From Day 0 up to 42 days
|
|
Reproductive system and breast disorders
Vulvovaginal discomfort
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
|
Vascular disorders
Hypertension
|
6.7%
1/15 • From Day 0 up to 42 days
|
0.00%
0/15 • From Day 0 up to 42 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place