A Study To Investigate Two 3-dose Schedules Of A Clostridium Difficile Vaccine In Healthy Adults Aged 65 to 85 Years

Phase 2

Completed

• Conditions: Clostridium Difficile Associated Disease
• Interventions: Biological: Clostridium difficile Vaccine; Biological: Placebo

• Registration Number: NCT02561195
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-07-09
• Study Start: 2015-07-16
• Study First Submitted QC: 2015-09-24
• Study First Posted: 2015-09-25
• Primary Completion: 2017-03-07
• Results First Submitted: 2018-03-05
• Results First Submitted QC: 2018-03-05
• Results First Posted: 2018-03-30
• Study Completion: 2020-02-13
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-11
• Last Update Posted: 2021-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Healthy male and female subjects
• Aged 65 to 85 years

Additional Inclusion Criteria for the extension Stage:

• Receipt of all 3 doses of C difficile vaccine (100 µg or 200 µg antigen dose level) in the original portion of the study.

Exclusion Criteria

• Proven or suspected prior episode of Clostridium difficile associated diarrhea
• Unstable chronic medical condition
• Disease requiring significant change in therapy or hospitalization for worsening disease within 8 weeks before receipt of study vaccine
• Serious chronic disorders
• Congenital or acquired immunodeficiency disorders
• Rheumatologic disorders or other illnesses requiring chronic treatment with known immunosuppressant medications.
• Active or treated leukemia or lymphoma or bone marrow disorder
• Any contraindication to vaccination or vaccine components including previous anaphylactic reaction to any vaccine or vaccine-related components

Additional Exclusion Criteria for the Extension Stage:

• Subjects originally randomized to placebo during the original portion of the study.
• Subjects who have already completed Visit 9 prior to study unblinding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High-dose C. difficile Vaccine (accelerated schedule)	Clostridium difficile Vaccine	-
Placebo (accelerated schedule)	Placebo	-
High-Dose C. difficile Vaccine (non-accelerated schedule)	Clostridium difficile Vaccine	-
Placebo (non-accelerated schedule)	Placebo	-
Low-dose C. difficile Vaccine (accelerated schedule)	Clostridium difficile Vaccine	-
Low-dose C. difficile Vaccine (non-accelerated schedule)	Clostridium difficile Vaccine	-

Primary Outcome Measures

Name	Time	Method
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Month 7	Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)	Toxin B antibodies (threshold \>= 2586 neutralization units/mL) were measured using neutralization assay.
Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2	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).
Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)	From Vaccination 1 up to 28 days after Vaccination 3 (Day 208)	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.
Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 1	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).
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Day 37	Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)	Toxin A antibodies (threshold \>= 219 neutralization units/mL) were measured using neutralization assay.
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Day 37	Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)	Toxin B antibodies (threshold \>= 2586 neutralization units/mL) were measured using neutralization assay.
Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2	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).
Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3	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).
Day 1, 8 and 30 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Day 37	Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)	Toxin A and B antibodies (threshold \>= 219 and 2586 neutralization units/mL) were measured using neutralization assay.
Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 3	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).
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin A at Month 7	Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)	Toxin A antibodies (threshold \>= 219 neutralization units/mL) were measured using neutralization assay.
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Both Toxin A and Toxin B at Month 7	Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)	Toxin A and B antibodies (threshold \>= 219 and 2586 neutralization units/mL) were measured using neutralization assay.
Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 7 Days After Vaccination 1	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).
Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3	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).
Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 7 Days After Vaccination 1	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).
Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 1	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).
Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 2	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).
Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 2	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).
Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 3	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).
Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Adverse Events (AEs)	From Vaccination 1 up to 28 days after Vaccination 3 (Day 58)	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.
Day 1, 8 and 30 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)	From Vaccination 1 up to 6 months after Vaccination 3 (Month 7)	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.
Month 0, 1 and 6 Regimen: Percentage of Participants With Treatment Emergent Serious Adverse Events (SAEs)	From Vaccination 1 up to 6 months after Vaccination 3 (Month 12)	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.

Secondary Outcome Measures

Name	Time	Method
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	Day 1, 8, 15, 30 and Month 2, 4, 7, 13	Toxin A antibodies were measured using neutralization assay.
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	Day 1, 8, 15, 30 and Month 2, 4, 7, 13	Toxin B antibodies were measured using neutralization assay.
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	Day 1, 30, 37, 187 and Month 2, 6, 12, 18	Toxin A and toxin B antibodies were measured using neutralization assay.
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	Day 30, 37, 187 and Month 2, 6, 7, 12, 18	Toxin A antibodies were measured using neutralization assay.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin A antibodies (threshold \>= 219 neutralization units/mL) were measured using neutralization assay.
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	Extension Stage Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	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.
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	Day 1, 8, 15, 30 and Month 2, 4, 7, 13	Toxin A and toxin B antibodies were measured using neutralization assay.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	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.
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	Day 1, 30, 37, 187 and Month 2, 6, 12, 18	Toxin A antibodies were measured using neutralization assay.
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	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.
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	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.
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	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.
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	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.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin A and B antibodies (threshold \>= 219 and 2586 neutralization units/mL) were measured using neutralization assay.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	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.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin B antibodies were measured using neutralization assay.
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	Day 1, 30, 37, 187 and Month 2, 6, 12, 18	Toxin B antibodies were measured using neutralization assay.
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	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.
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	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.
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	Day 8, 15, 30, 37 and Month 2, 4, 7, 13	Toxin A antibodies were measured using neutralization assay.
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	Day 8, 15, 30, 37 and Month 2, 4, 7, 13	Toxin B antibodies were measured using neutralization assay.
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	Day 8, 15, 30, 37 and Month 2, 4, 7, 13	Toxin A and toxin B antibodies were measured using neutralization assay.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin B antibodies (threshold \>= 2586 neutralization units/mL) were measured using neutralization assay.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	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.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin A and B antibodies were measured using neutralization assay.
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4	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.
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	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.
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	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.
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	Day 30, 37, 187 and Month 2, 6, 7, 12, 18	Toxin A antibodies were measured using neutralization assay.
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	Day 30, 37, 187 and Month 2, 6, 7, 12, 18	Toxin A and toxin B antibodies were measured using neutralization assay.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin A antibodies (threshold \>= 219 neutralization units/mL) were measured using neutralization assay.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin B antibodies (threshold \>= 2586 neutralization units/mL) were measured using neutralization assay.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin A and B antibodies (threshold \>= 219 and 2586 neutralization units/mL) were measured using neutralization assay.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	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.
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	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	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.
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Systemic Events by Severity Within 14 Days After Vaccination 4	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.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	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.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	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.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin A antibodies were measured using neutralization assay.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin A antibodies were measured using neutralization assay.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin B antibodies were measured using neutralization assay.
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	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4	Toxin A and B antibodies were measured using neutralization assay.
Extension Stage Day 1, 8 and 30 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4	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.
Extension Stage Month 0, 1 and 6 Regimen: Percentage of Participants With Local Reactions by Severity Within 14 Days After Vaccination 4	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.
Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)	From Vaccination 4 up to 28 days after Vaccination 4	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.
Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Adverse Events (AEs)	From Vaccination 4 up to 28 days after Vaccination 4	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.
Extension Stage Month 0, 1 and 6 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)	From Vaccination 4 up to 6 months after Vaccination 4	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.
Extension Stage Day 1, 8 and 30 Regimen: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)	From Vaccination 4 up to 6 months after Vaccination 4	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.

Trial Locations

Locations (16)

Vince & Associates Clinical Research, Inc.; 🇺🇸 Overland Park, Kansas, United States

Wake Research Associates, LLC; 🇺🇸 Raleigh, North Carolina, United States

Avail Clinical Research, LLC; 🇺🇸 DeLand, Florida, United States

QPS-MRA, LLC (Miami Research Associates); 🇺🇸 South Miami, Florida, United States

QPS-MRA, LLC (Broward Research Group); 🇺🇸 Hollywood, Florida, United States

East-West Medical Research Institute; 🇺🇸 Honolulu, Hawaii, United States

Vince & Associates Clinical Research, Inc; 🇺🇸 Overland Park, Kansas, United States

PMG Research of Wilmington, LLC; 🇺🇸 Wilmington, North Carolina, United States

Texas Center For Drug Development, Inc.; 🇺🇸 Houston, Texas, United States

Benchmark Research; 🇺🇸 Austin, Texas, United States

Clinical Research Center of Nevada LLC; 🇺🇸 Las Vegas, Nevada, United States

J. Lewis Research, Inc. / Foothill Family Clinic; 🇺🇸 Salt Lake City, Utah, United States

Cincinnati Childrens Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Clinical Trials of Texas, Inc.; 🇺🇸 San Antonio, Texas, United States

J. Lewis Research, Inc. / Foothill Family Clinic South; 🇺🇸 Salt Lake City, Utah, United States

Meridian Clinical Research, LLC; 🇺🇸 Omaha, Nebraska, United States