Trial Outcomes & Findings for Clostridium Difficile Vaccine Efficacy Trial (NCT NCT03090191)

Last Updated: 2023-02-13

Results Overview

CDI definition 1 for a primary episode of CDI (no previous CDI onset in the prior 8 weeks) was defined as either a) presence of diarrhea, defined as passage of 3 or more unformed stools (Bristol stool chart types 5-7) in 24 or fewer consecutive hours, and stool sample that was positive for the toxin B gene (by polymerase chain reaction \[PCR)\] and positive for toxin A and/or toxin B, as measured in the central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for the toxin B gene (via PCR) as measured in the central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

17535 participants

Primary outcome timeframe

From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)

Results posted on

2023-02-13

Participant Flow

A total of 18095 participants signed the informed consent form (ICF). Among that 560 participants did not meet all eligibility criteria, were not randomized and vaccinated. Overall, 17535 participants were randomized, out of which only 17440 participants received at least 1 dose of the investigational product.

Participant milestones

Participant milestones
Measure	Clostridium Difficile Vaccine Participants were randomized to Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo Participants were randomized to placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Overall Study STARTED	8766	8769
Overall Study Vaccinated at Month 0 (Dose 1)	8723	8717
Overall Study Received Clostridium Difficile Vaccine	7894	0
Overall Study Received Placebo	0	7967
Overall Study Vaccinated at Month 1 (Dose 2)	8311	8331
Overall Study Vaccinated at Month 6 (Dose 3)	7894	7967
Overall Study COMPLETED	5533	5574
Overall Study NOT COMPLETED	3233	3195

Reasons for withdrawal

Reasons for withdrawal
Measure	Clostridium Difficile Vaccine Participants were randomized to Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo Participants were randomized to placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Overall Study Adverse Event	90	72
Overall Study Death	365	358
Overall Study Lost to Follow-up	382	394
Overall Study Physician Decision	77	66
Overall Study Protocol Violation	43	52
Overall Study Withdrawal by Subject	2160	2133
Overall Study Site terminated	7	8
Overall Study Other	66	60
Overall Study Withdrawn before any study vaccination	43	52

Baseline Characteristics

Clostridium Difficile Vaccine Efficacy Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clostridium Difficile Vaccine n=8722 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8718 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.	Total n=17440 Participants Total of all reporting groups
Age, Continuous	68.0 Years STANDARD_DEVIATION 7.5 • n=93 Participants	68.1 Years STANDARD_DEVIATION 7.5 • n=4 Participants	68.0 Years STANDARD_DEVIATION 7.5 • n=27 Participants
Sex: Female, Male Female	4472 Participants n=93 Participants	4501 Participants n=4 Participants	8973 Participants n=27 Participants
Sex: Female, Male Male	4250 Participants n=93 Participants	4217 Participants n=4 Participants	8467 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1119 Participants n=93 Participants	1143 Participants n=4 Participants	2262 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7546 Participants n=93 Participants	7515 Participants n=4 Participants	15061 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	57 Participants n=93 Participants	60 Participants n=4 Participants	117 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	53 Participants n=93 Participants	54 Participants n=4 Participants	107 Participants n=27 Participants
Race (NIH/OMB) Asian	754 Participants n=93 Participants	725 Participants n=4 Participants	1479 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	20 Participants n=93 Participants	14 Participants n=4 Participants	34 Participants n=27 Participants
Race (NIH/OMB) Black or African American	663 Participants n=93 Participants	666 Participants n=4 Participants	1329 Participants n=27 Participants
Race (NIH/OMB) White	6891 Participants n=93 Participants	6922 Participants n=4 Participants	13813 Participants n=27 Participants
Race (NIH/OMB) More than one race	327 Participants n=93 Participants	322 Participants n=4 Participants	649 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	14 Participants n=93 Participants	15 Participants n=4 Participants	29 Participants n=27 Participants

PRIMARY outcome

Timeframe: From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)

Population: Per Protocol-3 analysis population included all randomized participants who received dose 1, dose 2, and dose 3 of the investigational product to which they were randomized and had no major protocol violations up to and including 14 days after dose 3. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=7707 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=7805 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 3	17 Episodes	25 Episodes

PRIMARY outcome

Timeframe: From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 months)

Population: Per Protocol-2 analysis population included all randomized participants who received dose 1 and dose 2 of the investigational product to which they were randomized and had no major protocol violations up to and including 14 days after dose 2. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

CDI definition 1 for a primary episode of CDI (no previous CDI onset in the prior 8 weeks) was defined as either a) presence of diarrhea, defined as passage of 3 or more unformed stools (Bristol stool chart types 5-7) in 24 or fewer consecutive hours, and stool sample that was positive for the toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in the central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for the toxin B gene (via PCR) as measured in the central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8139 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8184 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 2	24 Episodes	34 Episodes

PRIMARY outcome

Timeframe: Within 7 days after Dose 1 at Month 0

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Local reactions included redness, swelling and pain at injection site. These were recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 centimeter (cm) and graded as mild: 2.5 to 5.0 cm, moderate: greater than (\>) 5.0 to 10.0 cm, severe: \>10.0 cm. Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity. Grade 4 indicated emergency room visit or hospitalization.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8558 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8510 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Pain at injection site: Mild	17.5 Percentage of participants Interval 16.7 to 18.3	6.2 Percentage of participants Interval 5.7 to 6.8
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Redness: Mild	1.5 Percentage of participants Interval 1.3 to 1.8	0.6 Percentage of participants Interval 0.4 to 0.7
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Redness: Moderate	0.5 Percentage of participants Interval 0.4 to 0.7	0.3 Percentage of participants Interval 0.2 to 0.4
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Redness: Severe	0.4 Percentage of participants Interval 0.3 to 0.6	0.2 Percentage of participants Interval 0.1 to 0.3
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Redness: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Swelling: Mild	1.5 Percentage of participants Interval 1.3 to 1.8	0.5 Percentage of participants Interval 0.3 to 0.7
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Swelling: Moderate	0.9 Percentage of participants Interval 0.8 to 1.2	0.3 Percentage of participants Interval 0.2 to 0.5
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Swelling: Severe	0.3 Percentage of participants Interval 0.2 to 0.5	0.1 Percentage of participants Interval 0.0 to 0.2
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Swelling: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Pain at injection site: Moderate	2.2 Percentage of participants Interval 1.9 to 2.5	0.8 Percentage of participants Interval 0.6 to 1.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Pain at injection site: Severe	0.1 Percentage of participants Interval 0.0 to 0.2	0.1 Percentage of participants Interval 0.1 to 0.2
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 Pain at injection site: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0.1 Percentage of participants Interval 0.0 to 0.1

PRIMARY outcome

Timeframe: Within 7 days after Dose 2 at Month 1

Local reactions included redness, swelling and pain at injection site. These were recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: \> 5.0 to 10.0 cm, severe: \>10.0 cm. Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity. Grade 4 indicated emergency room visit or hospitalization.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8041 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8039 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Redness: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Swelling: Moderate	3.0 Percentage of participants Interval 2.6 to 3.4	0.2 Percentage of participants Interval 0.1 to 0.3
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Swelling: Severe	0.9 Percentage of participants Interval 0.7 to 1.1	0.1 Percentage of participants Interval 0.0 to 0.2
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Swelling: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Redness: Mild	2.6 Percentage of participants Interval 2.2 to 2.9	0.3 Percentage of participants Interval 0.2 to 0.5
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Redness: Moderate	2.2 Percentage of participants Interval 1.9 to 2.6	0.2 Percentage of participants Interval 0.1 to 0.3
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Redness: Severe	0.9 Percentage of participants Interval 0.7 to 1.2	0.1 Percentage of participants Interval 0.0 to 0.1
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Swelling: Mild	3.2 Percentage of participants Interval 2.8 to 3.6	0.3 Percentage of participants Interval 0.2 to 0.5
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Pain at injection site: Mild	23.0 Percentage of participants Interval 22.1 to 23.9	4.3 Percentage of participants Interval 3.9 to 4.8
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Pain at injection site: Moderate	4.5 Percentage of participants Interval 4.0 to 4.9	0.7 Percentage of participants Interval 0.5 to 0.9
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Pain at injection site: Severe	0.2 Percentage of participants Interval 0.1 to 0.3	0.1 Percentage of participants Interval 0.0 to 0.1
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 Pain at injection site: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: Within 7 days after Dose 3 at Month 6

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=7526 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=7569 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Redness: Mild	2.6 Percentage of participants Interval 2.3 to 3.0	0.4 Percentage of participants Interval 0.2 to 0.5
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Redness: Moderate	2.4 Percentage of participants Interval 2.1 to 2.8	0.2 Percentage of participants Interval 0.1 to 0.4
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Redness: Severe	0.7 Percentage of participants Interval 0.5 to 0.9	0.1 Percentage of participants Interval 0.0 to 0.1
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Redness: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Swelling: Mild	3.5 Percentage of participants Interval 3.1 to 3.9	0.3 Percentage of participants Interval 0.2 to 0.5
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Swelling: Moderate	3.3 Percentage of participants Interval 2.9 to 3.7	0.2 Percentage of participants Interval 0.1 to 0.4
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Swelling: Severe	0.8 Percentage of participants Interval 0.6 to 1.1	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Swelling: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Pain at injection site: Mild	21.0 Percentage of participants Interval 20.1 to 21.9	3.6 Percentage of participants Interval 3.2 to 4.1
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Pain at injection site: Moderate	4.5 Percentage of participants Interval 4.0 to 5.0	0.8 Percentage of participants Interval 0.6 to 1.0
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Pain at injection site: Severe	0.2 Percentage of participants Interval 0.1 to 0.4	0.1 Percentage of participants Interval 0.0 to 0.1
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 Pain at injection site: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: Within 7 days after Dose 1 at Month 0

Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild: (38.0 to 38.4 degree Celsius \[deg C\]), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), potentially life threatening (\> 40.0 deg C). Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8558 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8510 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Fatigue: Moderate	10.6 Percentage of participants Interval 10.0 to 11.3	10.4 Percentage of participants Interval 9.7 to 11.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Fever: 38.5-38.9 deg C	0.2 Percentage of participants Interval 0.1 to 0.3	0.2 Percentage of participants Interval 0.1 to 0.3
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Fever: 39.0-40.0 deg C	0.2 Percentage of participants Interval 0.1 to 0.3	0.1 Percentage of participants Interval 0.1 to 0.2
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Vomiting: Mild	1.1 Percentage of participants Interval 0.8 to 1.3	0.7 Percentage of participants Interval 0.5 to 0.9
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Fever: 38.0-38.4 deg C	0.5 Percentage of participants Interval 0.3 to 0.6	0.4 Percentage of participants Interval 0.3 to 0.5
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Fever: >40.0 deg C	0.1 Percentage of participants Interval 0.0 to 0.2	0.1 Percentage of participants Interval 0.0 to 0.2
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Fatigue: Mild	11.6 Percentage of participants Interval 10.9 to 12.3	10.2 Percentage of participants Interval 9.6 to 10.9
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Fatigue: Severe	1.1 Percentage of participants Interval 0.9 to 1.3	1.2 Percentage of participants Interval 1.0 to 1.5
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Fatigue: Grade 4	0.1 Percentage of participants Interval 0.0 to 0.1	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Headache: Mild	11.6 Percentage of participants Interval 10.9 to 12.3	10.1 Percentage of participants Interval 9.4 to 10.7
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Headache: Moderate	5.8 Percentage of participants Interval 5.3 to 6.3	5.4 Percentage of participants Interval 4.9 to 5.9
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Headache: Severe	0.5 Percentage of participants Interval 0.4 to 0.7	0.6 Percentage of participants Interval 0.5 to 0.8
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Headache: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Vomiting: Moderate	0.3 Percentage of participants Interval 0.2 to 0.4	0.2 Percentage of participants Interval 0.1 to 0.3
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Vomiting: Severe	0.1 Percentage of participants Interval 0.0 to 0.1	0.1 Percentage of participants Interval 0.0 to 0.1
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 Vomiting: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 New or worsening muscle pain: Mild	5.2 Percentage of participants Interval 4.7 to 5.7	3.9 Percentage of participants Interval 3.5 to 4.3
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 New or worsening muscle pain: Moderate	5.7 Percentage of participants Interval 5.2 to 6.2	5.6 Percentage of participants Interval 5.1 to 6.1
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 New or worsening muscle pain: Severe	0.6 Percentage of participants Interval 0.4 to 0.8	0.6 Percentage of participants Interval 0.5 to 0.8
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 New or worsening muscle pain: Grade 4	0.1 Percentage of participants Interval 0.0 to 0.1	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 New or worsening joint pain: Mild	4.0 Percentage of participants Interval 3.6 to 4.5	3.3 Percentage of participants Interval 2.9 to 3.7
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 New or worsening joint pain: Moderate	5.2 Percentage of participants Interval 4.7 to 5.7	5.0 Percentage of participants Interval 4.5 to 5.5
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 New or worsening joint pain: Severe	0.5 Percentage of participants Interval 0.4 to 0.7	0.5 Percentage of participants Interval 0.3 to 0.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 New or worsening joint pain: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: Within 7 days after Dose 2 at Month 1

Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild: (38.0 to 38.4 deg C), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), potentially life threatening (\> 40.0 deg C). Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8041 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8039 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Fatigue: Moderate	9.4 Percentage of participants Interval 8.7 to 10.0	9.0 Percentage of participants Interval 8.4 to 9.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Fever: 38.0-38.4 deg C	0.4 Percentage of participants Interval 0.3 to 0.6	0.4 Percentage of participants Interval 0.3 to 0.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Fever: 38.5-38.9 deg C	0.2 Percentage of participants Interval 0.1 to 0.3	0.1 Percentage of participants Interval 0.0 to 0.2
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Fever: 39.0-40.0 deg C	0.1 Percentage of participants Interval 0.0 to 0.2	0.2 Percentage of participants Interval 0.1 to 0.3
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Fever: >40.0 deg C	0.1 Percentage of participants Interval 0.0 to 0.1	0.1 Percentage of participants Interval 0.0 to 0.1
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Fatigue: Mild	10.2 Percentage of participants Interval 9.6 to 10.9	7.8 Percentage of participants Interval 7.2 to 8.4
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Fatigue: Severe	1.0 Percentage of participants Interval 0.8 to 1.2	1.0 Percentage of participants Interval 0.8 to 1.2
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Fatigue: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Headache: Mild	10.1 Percentage of participants Interval 9.4 to 10.8	8.3 Percentage of participants Interval 7.7 to 9.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Headache: Moderate	5.1 Percentage of participants Interval 4.6 to 5.6	5.5 Percentage of participants Interval 5.0 to 6.1
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Headache: Severe	0.5 Percentage of participants Interval 0.4 to 0.7	0.4 Percentage of participants Interval 0.3 to 0.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Headache: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Vomiting: Mild	0.8 Percentage of participants Interval 0.6 to 1.0	0.7 Percentage of participants Interval 0.5 to 0.9
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Vomiting: Moderate	0.2 Percentage of participants Interval 0.1 to 0.4	0.2 Percentage of participants Interval 0.1 to 0.3
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Vomiting: Severe	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 Vomiting: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 New or worsening muscle pain: Mild	4.8 Percentage of participants Interval 4.3 to 5.3	3.2 Percentage of participants Interval 2.9 to 3.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 New or worsening muscle pain: Moderate	5.1 Percentage of participants Interval 4.6 to 5.6	4.2 Percentage of participants Interval 3.8 to 4.7
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 New or worsening muscle pain: Severe	0.5 Percentage of participants Interval 0.4 to 0.7	0.6 Percentage of participants Interval 0.4 to 0.8
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 New or worsening muscle pain: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 New or worsening joint pain: Mild	3.8 Percentage of participants Interval 3.4 to 4.2	2.9 Percentage of participants Interval 2.6 to 3.3
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 New or worsening joint pain: Moderate	4.6 Percentage of participants Interval 4.1 to 5.0	3.9 Percentage of participants Interval 3.5 to 4.4
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 New or worsening joint pain: Severe	0.4 Percentage of participants Interval 0.3 to 0.6	0.5 Percentage of participants Interval 0.3 to 0.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 New or worsening joint pain: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: Within 7 days after Dose 3 at Month 6

Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by participants in an e-diary. Fever was categorized as: mild: (38.0 to 38.4 deg C), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), potentially life threatening (\> 40.0 deg C). Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalization. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: \>2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalization for hypotensive shock.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=7526 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=7569 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 New or worsening joint pain: Severe	0.4 Percentage of participants Interval 0.3 to 0.6	0.4 Percentage of participants Interval 0.3 to 0.5
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 New or worsening joint pain: Grade 4	0.1 Percentage of participants Interval 0.0 to 0.1	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Fever: 38.0-38.4 deg C	0.4 Percentage of participants Interval 0.3 to 0.6	0.2 Percentage of participants Interval 0.1 to 0.4
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Fever: 38.5-38.9 deg C	0.1 Percentage of participants Interval 0.1 to 0.2	0.1 Percentage of participants Interval 0.0 to 0.2
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Fever: 39.0-40.0 deg C	0.1 Percentage of participants Interval 0.1 to 0.2	0.1 Percentage of participants Interval 0.0 to 0.2
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Fever: >40.0 deg C	0.1 Percentage of participants Interval 0.0 to 0.1	0.1 Percentage of participants Interval 0.0 to 0.1
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Fatigue: Mild	9.2 Percentage of participants Interval 8.6 to 9.9	7.0 Percentage of participants Interval 6.4 to 7.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Fatigue: Moderate	9.4 Percentage of participants Interval 8.7 to 10.0	8.0 Percentage of participants Interval 7.4 to 8.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Fatigue: Severe	0.8 Percentage of participants Interval 0.6 to 1.0	0.8 Percentage of participants Interval 0.6 to 1.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Fatigue: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Headache: Mild	8.4 Percentage of participants Interval 7.8 to 9.0	7.9 Percentage of participants Interval 7.3 to 8.5
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Headache: Moderate	5.7 Percentage of participants Interval 5.1 to 6.2	4.7 Percentage of participants Interval 4.2 to 5.2
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Headache: Severe	0.3 Percentage of participants Interval 0.2 to 0.5	0.5 Percentage of participants Interval 0.3 to 0.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Headache: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Vomiting: Mild	0.6 Percentage of participants Interval 0.5 to 0.8	0.5 Percentage of participants Interval 0.4 to 0.7
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Vomiting: Moderate	0.1 Percentage of participants Interval 0.0 to 0.2	0.2 Percentage of participants Interval 0.1 to 0.3
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Vomiting: Severe	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 Vomiting: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 New or worsening muscle pain: Mild	4.0 Percentage of participants Interval 3.5 to 4.4	2.5 Percentage of participants Interval 2.2 to 2.9
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 New or worsening muscle pain: Moderate	4.8 Percentage of participants Interval 4.3 to 5.3	4.1 Percentage of participants Interval 3.6 to 4.6
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 New or worsening muscle pain: Severe	0.5 Percentage of participants Interval 0.3 to 0.7	0.5 Percentage of participants Interval 0.3 to 0.7
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 New or worsening muscle pain: Grade 4	0 Percentage of participants Interval 0.0 to 0.0	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 New or worsening joint pain: Mild	3.0 Percentage of participants Interval 2.6 to 3.4	2.5 Percentage of participants Interval 2.2 to 2.9
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 New or worsening joint pain: Moderate	4.4 Percentage of participants Interval 3.9 to 4.8	3.6 Percentage of participants Interval 3.2 to 4.0

PRIMARY outcome

Timeframe: From Day 1 of Dose 1 to 1 Month after Dose 3 (7 Months)

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product.

An AE was defined as any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and all non-serious adverse events. An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event. AEs included both SAEs and all Non-SAEs (except local and systemic events).

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8722 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8718 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of Participants Reporting Adverse Events (AEs) Any AEs	4161 Participants	4050 Participants
Number of Participants Reporting Adverse Events (AEs) Non-Serious AEs	3913 Participants	3791 Participants

PRIMARY outcome

Timeframe: From Day 1 of Dose 1 up to 6 months after Dose 3 (up to Month 12)

Population: Safety analysis population included all participants who received at least 1 dose of the investigational product.

An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8722 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8718 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of Participants Reporting Serious Adverse Events (SAEs)	719 Participants	722 Participants

SECONDARY outcome

Timeframe: From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)

CDI definition 1 for primary episode of CDI (no previous CDI onset in prior 8 weeks) and CDI definition 2 for recurrent episode (episode occurred 8 weeks or less after onset of previous episode \[provided symptoms of previous episode resolved\]) were both defined as either a) presence of diarrhea, (passage of 3 or more unformed stools \[Bristol stool chart types 5-7\]) in 24 or fewer consecutive hours, stool sample positive for toxin B gene (by PCR),positive for toxin A and/or toxin B, as measured in central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, surgery, histopathologically; and corresponding stool sample positive for toxin B gene (via PCR) as measured in central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=7707 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=7805 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of All Episodes of CDI (Definition 1 and 2) After Dose 3	28 Episodes	32 Episodes

SECONDARY outcome

Timeframe: From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)

Resolution of the event was the last day on which the event was recorded in the e-diary or the date the event ends if it was unresolved during the participant diary-recording period (end date collected on the case report form \[CRF\]). CDI definition 1 for a primary episode of CDI (no previous CDI onset in the prior 8 weeks) was defined as either a) presence of diarrhea, defined as passage of 3 or more unformed stools (Bristol stool chart types 5-7) in 24 or fewer consecutive hours, and stool sample that was positive for the toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in the central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for the toxin B gene (via PCR) as measured in the central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=17 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=24 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Time to Resolution for Participants With First Primary Episodes of CDI (Definition 1) After Dose 3	1.0 Days Interval 1.0 to 18.0	4.0 Days Interval 1.0 to 183.0

SECONDARY outcome

Timeframe: From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)

CDI definition 1 for a primary episode of CDI (no previous CDI onset in the prior 8 weeks) was defined as either a) presence of diarrhea, defined as passage of 3 or more unformed stools (Bristol stool chart types 5-7) in 24 or fewer consecutive hours, and stool sample that was positive for the toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in the central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for the toxin B gene (via PCR) as measured in the central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=17 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=25 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Proportion of Participants Who Required Medical Attention During First Primary Episode of CDI (Definition 1) After Dose 3	0 Proportion of participants	0.440 Proportion of participants

SECONDARY outcome

Timeframe: From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)

CDI definition 2 for a recurrent episode (an episode of CDI that occurred 8 weeks or less after the onset of a previous CDI episode \[provided the symptoms of the previous episode had resolved\]), was defined as either a) presence of diarrhea, defined as passage of 3 or more unformed stools (Bristol stool chart types 5-7) in 24 or fewer consecutive hours; and stool sample that was positive for the toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in the central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for the toxin B gene (by PCR) as measured in the central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=7707 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=7805 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 3	5 Participants	3 Participants

SECONDARY outcome

Timeframe: From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 months)

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8139 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8184 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of All Episodes of CDI (Definition 1 and 2) After Dose 2	37 Episodes	44 Episodes

SECONDARY outcome

Timeframe: From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 months)

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8139 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8184 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 2	6 Participants	3 Participants

SECONDARY outcome

Timeframe: From 14 days after Dose 2 to Dose 3 or the day the third vaccination was expected (168 days after Dose 2) for participants who received only 2 doses

CDI definition 1 for a primary episode of CDI (no previous CDI onset in the prior 8 weeks) was defined as either a) presence of diarrhea, defined as passage of 3 or more unformed stools (Bristol stool chart types 5-7) in 24 or fewer consecutive hours, and stool sample that was positive for the toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in the central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for the toxin B gene (via PCR) as measured in the central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases.

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8139 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8184 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of First Primary Episode of CDI (Definition 1) After Dose 2 and Before Dose 3	7 Episodes	8 Episodes

SECONDARY outcome

Timeframe: From 14 days after Dose 2 to Dose 3 or the day the third vaccination was expected (168 days after Dose 2) for participants who received only 2 doses

Outcome measures

Outcome measures
Measure	Clostridium Difficile Vaccine n=8139 Participants Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8184 Participants Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
Number of Participants With Recurrent Episode of CDI (Definition 2) After Dose 2 and Before Dose 3	1 Participants	0 Participants

Adverse Events

Clostridium Difficile Vaccine

Serious events: 719 serious events

Other events: 5702 other events

Deaths: 369 deaths

Placebo

Serious events: 722 serious events

Other events: 4314 other events

Deaths: 362 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Clostridium Difficile Vaccine n=8722 participants at risk Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.	Placebo n=8718 participants at risk Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6.
General disorders Fatigue (FATIGUE)	37.1% 3240/8722 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.	32.3% 2820/8718 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.
General disorders Injection site erythema (REDNESS)	21.5% 1879/8722 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.	7.5% 653/8718 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.
General disorders Injection site pain (PAIN)	41.2% 3596/8722 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.	12.1% 1056/8718 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.
General disorders Injection site swelling (SWELLING)	21.2% 1846/8722 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.	4.7% 414/8718 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.
Musculoskeletal and connective tissue disorders Arthralgia (JOINT PAIN)	18.1% 1583/8722 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.	15.5% 1354/8718 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.
Musculoskeletal and connective tissue disorders Myalgia (MUSCLE PAIN)	21.3% 1856/8722 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.	17.1% 1487/8718 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.
Nervous system disorders Headache (HEADACHE)	30.0% 2615/8722 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.	26.6% 2323/8718 • Local reactions and systemic events (included in other AEs): within 7 days after each dose (systematic assessment); SAEs: from Day 1 up to 6 months after last dose of vaccination (up to 12 months); other AEs: from Day 1 up to 1 month after last dose of vaccination (up to 7 months); All-Cause mortality: from Day 1 up to 6 months after last dose of vaccination (up to 12 months) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Cause of death was unknown. Safety analysis population included all participants who received at least 1 dose of the investigational product.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER