This study will investigate a Clostridium difficile vaccine in healthy adults aged 65-85 years. Each subject will initially receive 3 doses of vaccine on 1 of 2 vaccination schedules. The study will assess the safety and tolerability of the vaccine as well as the subjects' immune response to the vaccine. One year after the third dose subjects that did not receive placebo will be randomized to receive a fourth dose. Subjects will be followed for up to 4 years after their third vaccination.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
300
0.5 mL intramuscular injection.
0.5 mL intramuscular injection
Avail Clinical Research, LLC
DeLand, Florida, United States
QPS-MRA, LLC (Broward Research Group)
Hollywood, Florida, United States
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 37
Toxin A antibodies (threshold \>= 219 neutralization units/mL) were measured using neutralization assay.
Time frame: Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Month 7
Toxin A antibodies (threshold \>= 219 neutralization units/mL) were measured using neutralization assay.
Time frame: Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 37
Toxin B antibodies (threshold \>= 2586 neutralization units/mL) were measured using neutralization assay.
Time frame: Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Month 7
Toxin B antibodies (threshold \>= 2586 neutralization units/mL) were measured using neutralization assay.
Time frame: Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 37
Toxin A and B antibodies (threshold \>= 219 and 2586 neutralization units/mL) were measured using neutralization assay.
Time frame: Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Month 7
Toxin A and B antibodies (threshold \>= 219 and 2586 neutralization units/mL) were measured using neutralization assay.
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QPS-MRA, LLC (Miami Research Associates)
South Miami, Florida, United States
East-West Medical Research Institute
Honolulu, Hawaii, United States
Vince & Associates Clinical Research, Inc.
Overland Park, Kansas, United States
Vince & Associates Clinical Research, Inc
Overland Park, Kansas, United States
Meridian Clinical Research, LLC
Omaha, Nebraska, United States
Clinical Research Center of Nevada LLC
Las Vegas, Nevada, United States
Wake Research Associates, LLC
Raleigh, North Carolina, United States
PMG Research of Wilmington, LLC
Wilmington, North Carolina, United States
...and 7 more locations
Time frame: Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 7 Days After Vaccination 1
Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (grade 1) (did not interfere with activity), moderate (grade 2)(interfered with activity), severe (grade 3) (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 centimeter \[cm\]), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis).
Time frame: within 7 days After Vaccination 1
Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 1
Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis).
Time frame: within 14 days After Vaccination 1
Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2
Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis).
Time frame: within 14 days After Vaccination 2
Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2
Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis).
Time frame: within 14 days after Vaccination 2
Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3
Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis).
Time frame: within 14 days after Vaccination 3
Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3
Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis).
Time frame: within 14 days after Vaccination 3
Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 7 Days After Vaccination 1
Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 degree Celsius (C)), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (\>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (\>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).
Time frame: within 7 days after Vaccination 1
Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 1
Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (\>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (\>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).
Time frame: within 14 days after Vaccination 1
Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2
Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (\>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (\>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).
Time frame: within 14 days after Vaccination 2
Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2
Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (\>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (\>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).
Time frame: within 14 days after Vaccination 2
Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3
Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (\>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (\>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).
Time frame: within 14 days after Vaccination 3
Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3
Systemic events included fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain and were recorded by using an e-diary. Fever was graded as mild (38.0 to 38.4 C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade 4 (\>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours), severe (required intravenous hydration) and grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (\>=6 stools in 24 hours) and grade 4 (hospitalization). Headache, fatigue, new or worsening muscle pain and new or worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and grade 4 (hospitalization).
Time frame: within 14 days after Vaccination 3
Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Vaccination 1 up to 28 days after Vaccination 3 (Day 58)
Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Vaccination 1 up to 28 days after Vaccination 3 (Day 208)
Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events between first dose of study drug and up to 6 months after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Vaccination 1 up to 6 months after Vaccination 3 (Month 7)
Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events between first dose of study drug and up to 6 months after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Vaccination 1 up to 6 months after Vaccination 3 (Month 12)
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 1, 8, 15, 30, and Month 2, 4, 7, 13
Toxin A antibodies were measured using neutralization assay.
Time frame: Day 1, 8, 15, 30 and Month 2, 4, 7, 13
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 1, 8, 15, 30 and Month 2, 4, 7, 13
Toxin B antibodies were measured using neutralization assay.
Time frame: Day 1, 8, 15, 30 and Month 2, 4, 7, 13
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 1, 8, 15, 30 and Month 2, 4, 7, 13
Toxin A and toxin B antibodies were measured using neutralization assay.
Time frame: Day 1, 8, 15, 30 and Month 2, 4, 7, 13
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Toxin A antibodies were measured using neutralization assay.
Time frame: Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for for Toxin B at Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Toxin B antibodies were measured using neutralization assay.
Time frame: Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Toxin A and toxin B antibodies were measured using neutralization assay.
Time frame: Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Day 1, 8 and 30 Regimen: Geometric Mean Concentration of Toxin A Specific Neutralizing Antibody Levels at Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13
Geometric mean concentration (GMC) of toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. Confidence interval (CI) for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.
Time frame: Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13
Day 1, 8 and 30 Regimen: Geometric Mean Concentration of Toxin B Specific Neutralizing Antibody Levels at Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13
GMC of toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.
Time frame: Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13
Month 0, 1 and 6 Regimen: Geometric Mean Concentration of Toxin A Specific Neutralizing Antibody Levels at Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18
GMC of toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.
Time frame: Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18
Month 0, 1 and 6 Regimen: Geometric Mean Concentration of Toxin B Specific Neutralizing Antibody Levels at Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18
GMC of toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.
Time frame: Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18
Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Geometric mean fold rise (GMFR) in toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.
Time frame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 8, 15, 30, 37 and Month 2, 4, 7, 13
GMFR in toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.
Time frame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Day 30, 37, 187 and Month 2, 6, 7, 12, 18
GMFR in toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.
Time frame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 30, 37, 187 and Month 2, 6, 7, 12, 18
GMFR for toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.
Time frame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Toxin A antibodies were measured using neutralization assay.
Time frame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Toxin B antibodies were measured using neutralization assay.
Time frame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving>=4,>=8,>=16,>=32 Fold Rise From Baseline in Both Toxin A and Toxin B Specific Antibody Levels at Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Toxin A and toxin B antibodies were measured using neutralization assay.
Time frame: Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Toxin A antibodies were measured using neutralization assay.
Time frame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Toxin A antibodies were measured using neutralization assay.
Time frame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving>=4,>=8,>=16,>=32 Fold Rise From Baseline in Both Toxin A and Toxin B Antibody Levels at Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Toxin A and toxin B antibodies were measured using neutralization assay.
Time frame: Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin A antibodies (threshold \>= 219 neutralization units/mL) were measured using neutralization assay.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin B antibodies (threshold \>= 2586 neutralization units/mL) were measured using neutralization assay.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin A and B antibodies (threshold \>= 219 and 2586 neutralization units/mL) were measured using neutralization assay.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin A antibodies (threshold \>= 219 neutralization units/mL) were measured using neutralization assay.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin B antibodies (threshold \>= 2586 neutralization units/mL) were measured using neutralization assay.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin A and B antibodies (threshold \>= 219 and 2586 neutralization units/mL) were measured using neutralization assay.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Concentration for Toxin A Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
GMC of toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Concentration for Toxin B Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
GMC of toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.
Time frame: Extension Stage Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Concentration for Toxin A Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
GMC of toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Concentration for Toxin B Specific Neutralizing Antibody Levels at Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36
GMC of toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of assay results. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of concentrations.
Time frame: Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
GMFR in toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Day 8, 30 and Months 6, 12, 18, 24, 30, 36
GMFR in toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin A Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
GMFR in toxin A specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Geometric Mean Fold Rise in Toxin B Specific Neutralizing Antibody Levels From Baseline at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
GMFR in toxin B specific antibody levels was calculated using back transformations of the logarithmically transformed means of fold rise from baseline with assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin A antibodies were measured using neutralization assay.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin B antibodies were measured using neutralization assay.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Both Toxin A and Toxin B Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin A and B antibodies were measured using neutralization assay.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin A Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin A antibodies were measured using neutralization assay.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Toxin B Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin B antibodies were measured using neutralization assay.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants Achieving >=4, >=8, >=16 and >=32 Fold Rise From Baseline in Both Toxin A and Toxin B Specific Antibody Levels at Days 8, 30 and Months 6, 12, 18, 24, 30, 36
Toxin A and B antibodies were measured using neutralization assay.
Time frame: Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4
Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (grade 1) (did not interfere with activity), moderate (grade 2) (interfered with activity), severe (grade 3) (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis). Any local reaction referred to any injection site pain, any swelling, or any redness.
Time frame: Within 14 days after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4
Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (grade 1) (did not interfere with activity), moderate (grade 2) (interfered with activity), severe (grade 3) (prevented daily activity) and grade 4 (emergency room visit or hospitalization). Redness and swelling were graded as: mild (2.5-5.0 cm), moderate (\>5.0 to 10.0 cm), severe (\>10.0 cm) and grade 4 (necrosis). Any local reaction referred to any injection site pain, any swelling, or any redness.
Time frame: Within 14 days after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4
Systemic events included following events: Fever was graded as mild (38.0 to 38.4 degree C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade (G) 4 (\>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours), severe (required intravenous hydration)/grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (\>=6 stools in 24 hours) and G4 (hospitalization). Headache, fatigue, new/worsening muscle pain and new/worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and G4 (hospitalization). Any systemic event referred to any fever \>= 38.0 degree C, any vomiting, any diarrhea, any headache, any fatigue, any new/worsening muscle pain, or any new or worsening joint pain.
Time frame: Within 14 days after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4
Systemic events included following events: Fever was graded as mild (38.0 to 38.4 degree C), moderate (38.5 to 38.9 degree C), severe (39.0 to 40.0 degree C), grade (G) 4 (\>40.0 degree C). Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours), severe (required intravenous hydration)/grade 4 (hospitalization for hypotensive shock). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours), severe (\>=6 stools in 24 hours) and G4 (hospitalization). Headache, fatigue, new/worsening muscle pain and new/worsening joint pain was graded as mild (no interference with activity), moderate (some interference with activity), severe (prevents daily activity) and G4 (hospitalization). Any systemic event referred to any fever \>= 38.0 degree C, any vomiting, any diarrhea, any headache, any fatigue, any new/worsening muscle pain, or any new or worsening joint pain.
Time frame: within 14 days after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent adverse events are events from dose 4 of study drug to 28 days after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Vaccination 4 up to 28 days after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent adverse events are events from dose 4 of study drug to 28 days after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Vaccination 4 up to 28 days after Vaccination 4
Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events from dose 4 of study drug to 6 months after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Vaccination 4 up to 6 months after Vaccination 4
Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. Treatment-emergent serious adverse events are events from dose 4 of study drug to 6 months after dose 4 of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Vaccination 4 up to 6 months after Vaccination 4