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

Clostridium Difficile Associated Disease Clinical Trial

Official title:

A PHASE 2, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF TWO 3-DOSE REGIMENS OF A CLOSTRIDIUM DIFFICILE VACCINE IN HEALTHY ADULTS AGED 65 TO 85 YEARS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02561195
• Other study ID #: B5091009
• Status: Completed
• Phase: Phase 2
• Start date: July 16, 2015
• Est. completion date: February 13, 2020

Study information

• Verified date: February 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: February 13, 2020
• Est. primary completion date: March 7, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Clostridium Difficile Associated Disease
• Clostridium Infections

Intervention

Biological:
• Clostridium difficile Vaccine
0.5 mL intramuscular injection.
• Placebo
0.5 mL intramuscular injection

Locations

Country	Name	City	State
United States	Benchmark Research	Austin	Texas
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	QPS-MRA, LLC (Broward Research Group)	Hollywood	Florida
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Texas Center For Drug Development, Inc.	Houston	Texas
United States	Clinical Research Center of Nevada LLC	Las Vegas	Nevada
United States	Meridian Clinical Research, LLC	Omaha	Nebraska
United States	Vince & Associates Clinical Research, Inc	Overland Park	Kansas
United States	Vince & Associates Clinical Research, Inc.	Overland Park	Kansas
United States	Wake Research Associates, LLC	Raleigh	North Carolina
United States	J. Lewis Research, Inc. / Foothill Family Clinic	Salt Lake City	Utah
United States	J. Lewis Research, Inc. / Foothill Family Clinic South	Salt Lake City	Utah
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	QPS-MRA, LLC (Miami Research Associates)	South Miami	Florida
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
Primary	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.	Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
Primary	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.	Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
Primary	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.	Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
Primary	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.	Day 37 (7 days after Vaccination 3 of Day 1, 8 and 30 regimen)
Primary	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.	Month 7 (1 month after Vaccination 3 of Month 0, 1 and 6 regimen)
Primary	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).	within 7 days After Vaccination 1
Primary	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).	within 14 days After Vaccination 1
Primary	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).	within 14 days After Vaccination 2
Primary	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).	within 14 days after Vaccination 2
Primary	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).	within 14 days after Vaccination 3
Primary	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).	within 14 days after Vaccination 3
Primary	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).	within 7 days after Vaccination 1
Primary	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).	within 14 days after Vaccination 1
Primary	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).	within 14 days after Vaccination 2
Primary	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).	within 14 days after Vaccination 2
Primary	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).	within 14 days after Vaccination 3
Primary	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).	within 14 days after Vaccination 3
Primary	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.	From Vaccination 1 up to 28 days after Vaccination 3 (Day 58)
Primary	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.	From Vaccination 1 up to 28 days after Vaccination 3 (Day 208)
Primary	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.	From Vaccination 1 up to 6 months after Vaccination 3 (Month 7)
Primary	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.	From Vaccination 1 up to 6 months after Vaccination 3 (Month 12)
Secondary	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.	Day 1, 8, 15, 30 and Month 2, 4, 7, 13
Secondary	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.	Day 1, 8, 15, 30 and Month 2, 4, 7, 13
Secondary	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.	Day 1, 8, 15, 30 and Month 2, 4, 7, 13
Secondary	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.	Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Secondary	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.	Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Secondary	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.	Day 1, 30, 37, 187 and Month 2, 6, 12, 18
Secondary	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.	Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13
Secondary	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.	Day 1, 8, 15, 30, 37 and Month 2, 4, 7, 13
Secondary	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.	Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18
Secondary	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.	Day 1, 30, 37, 187 and Month 2, 6, 7, 12, 18
Secondary	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.	Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Secondary	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.	Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Secondary	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.	Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Secondary	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.	Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Secondary	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.	Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Secondary	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.	Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Secondary	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.	Day 8, 15, 30, 37 and Month 2, 4, 7, 13
Secondary	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.	Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Secondary	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.	Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Secondary	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.	Day 30, 37, 187 and Month 2, 6, 7, 12, 18
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Extension Stage Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 1, 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Days 8, 30 and Months 6, 12, 18, 24, 30, 36 after Vaccination 4
Secondary	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.	Within 14 days after Vaccination 4
Secondary	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.	Within 14 days after Vaccination 4
Secondary	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.	Within 14 days after Vaccination 4
Secondary	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.	within 14 days after Vaccination 4
Secondary	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.	From Vaccination 4 up to 28 days after Vaccination 4
Secondary	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.	From Vaccination 4 up to 28 days after Vaccination 4
Secondary	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.	From Vaccination 4 up to 6 months after Vaccination 4
Secondary	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.	From Vaccination 4 up to 6 months after Vaccination 4

External Links

•   To obtain contact information for a study center near you, click here.