Clostridium Difficile Infection
Conditions
Brief summary
The Clover trial is evaluating an investigational vaccine that may help to prevent Clostridium difficile infection. Participants in the study are adults 50 years of age and older, who are at risk of developing Clostridium difficile infection. The study will assess whether the vaccine prevents the disease, and whether it is safe and well tolerated. Each subject will receive 3 doses of Clostridium difficile vaccine or placebo and be followed for up to 3 years after vaccination for potential Clostridium difficile infection.
Interventions
BIOLOGICALClostridium difficile vaccine
Toxoid-based Clostridium difficile vaccine
BIOLOGICALPlacebo
Normal saline solution (0.9% sodium chloride)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Evidence of a personally signed and dated informed consent document. * Willing and able to comply with study procedures. * Subjects with an increased risk of future contact with healthcare systems or subjects who have received systemic antibiotics in the previous 12 weeks. * Ability to be contacted by telephone during study participation. * Negative urine pregnancy test for female subjects of childbearing potential.
Exclusion criteria
* Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study. * Participation in other studies involving investigational drug(s)/vaccine(s) within 28 days prior to study entry until 1 month after the third vaccination. * Previous administration of an investigational C difficile vaccine or C difficile mAb therapy. * Prior episode of CDI.. * Receipt of blood products or immunoglobulins within 6 months before enrollment. * Subjects who may be unable to respond to vaccination due to: * Metastatic malignancy; or * End-stage renal disease; or * Any serious medical disorder likely to be fatal within the next 12 months; or * Congenital or acquired immunodeficiency; or * Receipt of high dose systemic corticosteroids for 14 days within 28 days of enrollment; or * Receipt of chronic systemic treatment with other known immunosuppressant medications, or radiotherapy, within 6 months of enrollment. * Known infection with human immunodeficiency virus (HIV). * Any bleeding disorder or anticoagulant therapy that would contraindicate intramuscular injection. * Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components. * Prior small- or large-bowel resection. * Any condition or treatment resulting in frequent diarrhea. * Other acute or chronic condition or abnormality that may increase the risk associated with study participation or IP administration or may interfere with interpretation of study results * Pregnant or breastfeeding female subjects; male subjects and female subjects who are sexually active and at risk for pregnancy and will not/cannot use 2 methods of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Serious Adverse Events (SAEs) | From Day 1 of Dose 1 up to 6 months after Dose 3 (up to Month 12) | 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. |
| Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 2 | From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 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. |
| Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Within 7 days after Dose 1 at Month 0 | 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. |
| Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | 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. |
| Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Within 7 days after Dose 3 at Month 6 | 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. |
| Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | 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. |
| Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | 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. |
| Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | 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. |
| Number of Participants Reporting Adverse Events (AEs) | From Day 1 of Dose 1 to 1 Month after Dose 3 (7 Months) | 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). |
| Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 3 | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Resolution for Participants With First Primary Episodes of CDI (Definition 1) After Dose 3 | 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. |
| Proportion of Participants Who Required Medical Attention During First Primary Episode of CDI (Definition 1) After Dose 3 | 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. |
| Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 3 | 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. |
| Number of All Episodes of CDI (Definition 1 and 2) After Dose 2 | From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 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. |
| Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 2 | From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 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. |
| Number of First Primary Episode of CDI (Definition 1) After Dose 2 and Before Dose 3 | 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. |
| Number of Participants With Recurrent Episode of CDI (Definition 2) After Dose 2 and Before Dose 3 | 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 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. |
| Number of All Episodes of CDI (Definition 1 and 2) After Dose 3 | 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. |
Countries
Argentina, Australia, Belgium, Bulgaria, Canada, Chile, Colombia, Czechia, Finland, France, Germany, Hungary, Japan, Peru, Poland, Portugal, Slovakia, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Clostridium Difficile Vaccine Participants who received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6. | 8,722 |
| Placebo Participants who received placebo (normal saline solution of 0.9 percent \[%\] sodium chloride) intramuscularly at Months 0, 1 and 6. | 8,718 |
| Total | 17,440 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 90 | 72 |
| Overall Study | Death | 365 | 358 |
| Overall Study | Lost to Follow-up | 382 | 394 |
| Overall Study | Other | 66 | 60 |
| Overall Study | Physician Decision | 77 | 66 |
| Overall Study | Protocol Violation | 43 | 52 |
| Overall Study | Site terminated | 7 | 8 |
| Overall Study | Withdrawal by Subject | 2,160 | 2,133 |
| Overall Study | Withdrawn before any study vaccination | 43 | 52 |
Baseline characteristics
| Characteristic | Placebo | Total | Clostridium Difficile Vaccine |
|---|---|---|---|
| Age, Continuous | 68.1 Years STANDARD_DEVIATION 7.5 | 68.0 Years STANDARD_DEVIATION 7.5 | 68.0 Years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1143 Participants | 2262 Participants | 1119 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7515 Participants | 15061 Participants | 7546 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 60 Participants | 117 Participants | 57 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 54 Participants | 107 Participants | 53 Participants |
| Race (NIH/OMB) Asian | 725 Participants | 1479 Participants | 754 Participants |
| Race (NIH/OMB) Black or African American | 666 Participants | 1329 Participants | 663 Participants |
| Race (NIH/OMB) More than one race | 322 Participants | 649 Participants | 327 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 14 Participants | 34 Participants | 20 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 29 Participants | 14 Participants |
| Race (NIH/OMB) White | 6922 Participants | 13813 Participants | 6891 Participants |
| Sex: Female, Male Female | 4501 Participants | 8973 Participants | 4472 Participants |
| Sex: Female, Male Male | 4217 Participants | 8467 Participants | 4250 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 369 / 8,722 | 362 / 8,718 |
| other Total, other adverse events | 5,702 / 8,722 | 4,314 / 8,718 |
| serious Total, serious adverse events | 719 / 8,722 | 722 / 8,718 |
Outcome results
Primary
Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 2
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 2 | 24 Episodes |
| Placebo | Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 2 | 34 Episodes |
96.4% CI: [-28.4, 61]
Primary
Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 3
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 3 | 17 Episodes |
| Placebo | Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 3 | 25 Episodes |
96.4% CI: [-38.7, 66.6]
Primary
Number of Participants Reporting Adverse Events (AEs)
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).
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clostridium Difficile Vaccine | Number of Participants Reporting Adverse Events (AEs) | Any AEs | 4161 Participants |
| Clostridium Difficile Vaccine | Number of Participants Reporting Adverse Events (AEs) | Non-Serious AEs | 3913 Participants |
| Placebo | Number of Participants Reporting Adverse Events (AEs) | Non-Serious AEs | 3791 Participants |
| Placebo | Number of Participants Reporting Adverse Events (AEs) | Any AEs | 4050 Participants |
Primary
Number of Participants Reporting Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of Participants Reporting Serious Adverse Events (SAEs) | 719 Participants |
| Placebo | Number of Participants Reporting Serious Adverse Events (SAEs) | 722 Participants |
Primary
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Redness: Mild | 1.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Redness: Moderate | 0.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Redness: Severe | 0.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Redness: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Swelling: Mild | 1.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Swelling: Moderate | 0.9 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Swelling: Severe | 0.3 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Swelling: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Pain at injection site: Mild | 17.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Pain at injection site: Moderate | 2.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Pain at injection site: Severe | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Pain at injection site: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Pain at injection site: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Redness: Mild | 0.6 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Swelling: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Redness: Moderate | 0.3 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Pain at injection site: Moderate | 0.8 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Redness: Severe | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Swelling: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Redness: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Pain at injection site: Grade 4 | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Swelling: Mild | 0.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Pain at injection site: Mild | 6.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 1 | Swelling: Moderate | 0.3 Percentage of participants |
Primary
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2
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.
Time frame: Within 7 days after Dose 2 at Month 1
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Redness: Mild | 2.6 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Redness: Moderate | 2.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Redness: Severe | 0.9 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Redness: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Swelling: Mild | 3.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Swelling: Moderate | 3.0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Swelling: Severe | 0.9 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Swelling: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Pain at injection site: Mild | 23.0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Pain at injection site: Moderate | 4.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Pain at injection site: Severe | 0.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Pain at injection site: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Pain at injection site: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Redness: Mild | 0.3 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Swelling: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Redness: Moderate | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Pain at injection site: Moderate | 0.7 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Redness: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Swelling: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Redness: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Pain at injection site: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Swelling: Mild | 0.3 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Pain at injection site: Mild | 4.3 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 2 | Swelling: Moderate | 0.2 Percentage of participants |
Primary
Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3
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.
Time frame: Within 7 days after Dose 3 at Month 6
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Redness: Mild | 2.6 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Redness: Moderate | 2.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Redness: Severe | 0.7 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Redness: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Swelling: Mild | 3.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Swelling: Moderate | 3.3 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Swelling: Severe | 0.8 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Swelling: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Pain at injection site: Mild | 21.0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Pain at injection site: Moderate | 4.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Pain at injection site: Severe | 0.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Pain at injection site: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Pain at injection site: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Redness: Mild | 0.4 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Swelling: Severe | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Redness: Moderate | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Pain at injection site: Moderate | 0.8 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Redness: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Swelling: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Redness: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Pain at injection site: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Swelling: Mild | 0.3 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Pain at injection site: Mild | 3.6 Percentage of participants |
| Placebo | Percentage of Participants Reporting Local Reactions Within 7 Days After Dose 3 | Swelling: Moderate | 0.2 Percentage of participants |
Primary
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 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 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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fatigue: Severe | 1.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fever: 38.5-38.9 deg C | 0.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fever: 39.0-40.0 deg C | 0.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fever: >40.0 deg C | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fatigue: Mild | 11.6 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fatigue: Moderate | 10.6 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fever: 38.0-38.4 deg C | 0.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fatigue: Grade 4 | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Headache: Mild | 11.6 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Headache: Moderate | 5.8 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Headache: Severe | 0.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Headache: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Vomiting: Mild | 1.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Vomiting: Moderate | 0.3 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Vomiting: Severe | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Vomiting: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening muscle pain: Mild | 5.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening muscle pain: Moderate | 5.7 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening muscle pain: Severe | 0.6 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening muscle pain: Grade 4 | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening joint pain: Mild | 4.0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening joint pain: Moderate | 5.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening joint pain: Severe | 0.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening joint pain: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening joint pain: Severe | 0.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fever: 38.0-38.4 deg C | 0.4 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Vomiting: Mild | 0.7 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fever: 38.5-38.9 deg C | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening muscle pain: Severe | 0.6 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fever: 39.0-40.0 deg C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Vomiting: Moderate | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fever: >40.0 deg C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening joint pain: Moderate | 5.0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fatigue: Mild | 10.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Vomiting: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fatigue: Moderate | 10.4 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening muscle pain: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fatigue: Severe | 1.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Vomiting: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Fatigue: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening joint pain: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Headache: Mild | 10.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening muscle pain: Mild | 3.9 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Headache: Moderate | 5.4 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening joint pain: Mild | 3.3 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Headache: Severe | 0.6 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | New or worsening muscle pain: Moderate | 5.6 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 | Headache: Grade 4 | 0 Percentage of participants |
Primary
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2
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.
Time frame: Within 7 days after Dose 2 at Month 1
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 and ''number analyzed'' signifies number of participants evaluable at specific rows.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fatigue: Severe | 1.0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fever: 38.5-38.9 deg C | 0.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fever: 39.0-40.0 deg C | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fever: >40.0 deg C | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fatigue: Mild | 10.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fatigue: Moderate | 9.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fever: 38.0-38.4 deg C | 0.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fatigue: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Headache: Mild | 10.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Headache: Moderate | 5.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Headache: Severe | 0.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Headache: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Vomiting: Mild | 0.8 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Vomiting: Moderate | 0.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Vomiting: Severe | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Vomiting: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening muscle pain: Mild | 4.8 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening muscle pain: Moderate | 5.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening muscle pain: Severe | 0.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening muscle pain: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening joint pain: Mild | 3.8 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening joint pain: Moderate | 4.6 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening joint pain: Severe | 0.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening joint pain: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening joint pain: Severe | 0.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fever: 38.0-38.4 deg C | 0.4 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Vomiting: Mild | 0.7 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fever: 38.5-38.9 deg C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening muscle pain: Severe | 0.6 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fever: 39.0-40.0 deg C | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Vomiting: Moderate | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fever: >40.0 deg C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening joint pain: Moderate | 3.9 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fatigue: Mild | 7.8 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Vomiting: Severe | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fatigue: Moderate | 9.0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening muscle pain: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fatigue: Severe | 1.0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Vomiting: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Fatigue: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening joint pain: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Headache: Mild | 8.3 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening muscle pain: Mild | 3.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Headache: Moderate | 5.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening joint pain: Mild | 2.9 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Headache: Severe | 0.4 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | New or worsening muscle pain: Moderate | 4.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 2 | Headache: Grade 4 | 0 Percentage of participants |
Primary
Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3
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.
Time frame: Within 7 days after Dose 3 at Month 6
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 and ''number analyzed'' signifies number of participants evaluable at specific rows.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Headache: Moderate | 5.7 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fever: 39.0-40.0 deg C | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fatigue: Mild | 9.2 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fatigue: Moderate | 9.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fatigue: Severe | 0.8 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fatigue: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Headache: Mild | 8.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fever: 38.5-38.9 deg C | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Headache: Severe | 0.3 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Headache: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Vomiting: Mild | 0.6 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Vomiting: Moderate | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Vomiting: Severe | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Vomiting: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening muscle pain: Mild | 4.0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening muscle pain: Moderate | 4.8 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening muscle pain: Severe | 0.5 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening muscle pain: Grade 4 | 0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening joint pain: Mild | 3.0 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening joint pain: Moderate | 4.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening joint pain: Severe | 0.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening joint pain: Grade 4 | 0.1 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fever: 38.0-38.4 deg C | 0.4 Percentage of participants |
| Clostridium Difficile Vaccine | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fever: >40.0 deg C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening joint pain: Moderate | 3.6 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fever: 38.5-38.9 deg C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Vomiting: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fever: 39.0-40.0 deg C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening muscle pain: Mild | 2.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fatigue: Moderate | 8.0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening joint pain: Severe | 0.4 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fatigue: Severe | 0.8 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening muscle pain: Moderate | 4.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fatigue: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fatigue: Mild | 7.0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Headache: Mild | 7.9 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening muscle pain: Severe | 0.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Headache: Moderate | 4.7 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening joint pain: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Headache: Severe | 0.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening muscle pain: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Headache: Grade 4 | 0 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fever: >40.0 deg C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Vomiting: Mild | 0.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | New or worsening joint pain: Mild | 2.5 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Vomiting: Moderate | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Fever: 38.0-38.4 deg C | 0.2 Percentage of participants |
| Placebo | Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 3 | Vomiting: Severe | 0 Percentage of participants |
Secondary
Number of All Episodes of CDI (Definition 1 and 2) After Dose 2
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of All Episodes of CDI (Definition 1 and 2) After Dose 2 | 37 Episodes |
| Placebo | Number of All Episodes of CDI (Definition 1 and 2) After Dose 2 | 44 Episodes |
98.2% CI: [-74.6, 58.5]
Secondary
Number of All Episodes of CDI (Definition 1 and 2) After Dose 3
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of All Episodes of CDI (Definition 1 and 2) After Dose 3 | 28 Episodes |
| Placebo | Number of All Episodes of CDI (Definition 1 and 2) After Dose 3 | 32 Episodes |
98.2% CI: [-110.7, 62.5]
Secondary
Number of First Primary Episode of CDI (Definition 1) After Dose 2 and Before Dose 3
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.
Time frame: 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
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of First Primary Episode of CDI (Definition 1) After Dose 2 and Before Dose 3 | 7 Episodes |
| Placebo | Number of First Primary Episode of CDI (Definition 1) After Dose 2 and Before Dose 3 | 8 Episodes |
98.2% CI: [-246.7, 78.5]
Secondary
Number of Participants With Recurrent Episode of CDI (Definition 2) After Dose 2 and Before Dose 3
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.
Time frame: 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
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of Participants With Recurrent Episode of CDI (Definition 2) After Dose 2 and Before Dose 3 | 1 Participants |
| Placebo | Number of Participants With Recurrent Episode of CDI (Definition 2) After Dose 2 and Before Dose 3 | 0 Participants |
Secondary
Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 2
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 2 | 6 Participants |
| Placebo | Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 2 | 3 Participants |
98.2% CI: [-1770.1, 67.2]
Secondary
Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 3
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clostridium Difficile Vaccine | Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 3 | 5 Participants |
| Placebo | Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 3 | 3 Participants |
98.2% CI: [-1533.1, 75.6]
Secondary
Proportion of Participants Who Required Medical Attention During First Primary Episode of CDI (Definition 1) After Dose 3
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clostridium Difficile Vaccine | Proportion of Participants Who Required Medical Attention During First Primary Episode of CDI (Definition 1) After Dose 3 | 0 Proportion of participants |
| Placebo | Proportion of Participants Who Required Medical Attention During First Primary Episode of CDI (Definition 1) After Dose 3 | 0.440 Proportion of participants |
98.2% CI: [0, 0.81]
Secondary
Time to Resolution for Participants With First Primary Episodes of CDI (Definition 1) After Dose 3
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clostridium Difficile Vaccine | Time to Resolution for Participants With First Primary Episodes of CDI (Definition 1) After Dose 3 | 1.0 Days |
| Placebo | Time to Resolution for Participants With First Primary Episodes of CDI (Definition 1) After Dose 3 | 4.0 Days |
p-value: 0.0172Wilcoxon Rank Sum Test (2-sided)