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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 300
- 试验地点
- 33
- 主要终点
- Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Month 7
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Month 0, 1 and 6 Regimen: Percentage of Participants Achieving Prespecified Antibody Titer Level for Toxin B at Month 7
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)