A Phase 3 interventional study of Clostridium difficile vaccine and Placebo in Clostridium Difficile Infection, sponsored by Pfizer. Completed at 426 sites in 23 countries. Open to participants aged 50 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-02-13.
Sponsored by Pfizer · Phase 3, Interventional, and Prevention
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.
310 studies on the registry are indexed under Clostridium Infections; 50 are open to participants now.
This study's enrollment of 17,535 is above the median of 65 across 233 interventional studies indexed under Clostridium Infections.
Browse Clostridium Infections studies →Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Subjects who may be unable to respond to vaccination due to:
Biological: Clostridium difficile vaccine
Biological: Placebo
Toxoid-based Clostridium difficile vaccine
Normal saline solution (0.9% sodium chloride)
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)
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)
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
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
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
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
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
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
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)
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)
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)
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)
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)
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)
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)
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)
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
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
| Milestone | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Started | 8766 | 8769 |
| Vaccinated at month 0 (dose 1) | 8723 | 8717 |
| Received clostridium difficile vaccine | 8721 | 1 |
| Received placebo | 2 | 8716 |
| Vaccinated at month 1 (dose 2) | 8311 | 8331 |
| Received clostridium difficile vaccine | 8310 | 0 |
| Received placebo | 1 | 8331 |
| Vaccinated at month 6 (dose 3) | 7894 | 7967 |
| Received clostridium difficile vaccine | 7894 | 0 |
| Received placebo | 0 | 7967 |
| Completed | 5533 | 5574 |
| Not completed | 3233 | 3195 |
| Withdrew: Adverse event | 90 | 72 |
| Withdrew: Death | 365 | 358 |
| Withdrew: Lost to follow-up | 382 | 394 |
| Withdrew: Physician decision | 77 | 66 |
| Withdrew: Protocol violation | 43 | 52 |
| Withdrew: Withdrawal by subject | 2160 | 2133 |
| Withdrew: Site terminated | 7 | 8 |
| Withdrew: Other | 66 | 60 |
| Withdrew: Withdrawn before any study vaccination | 43 | 52 |
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.
| Episodes | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 3 | 17 | 25 |
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.
| Episodes | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 2 | 24 | 34 |
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 | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Redness: Mild | 1.5 (1.3 to 1.8) | 0.6 (0.4 to 0.7) |
| Redness: Moderate | 0.5 (0.4 to 0.7) | 0.3 (0.2 to 0.4) |
| Redness: Severe | 0.4 (0.3 to 0.6) | 0.2 (0.1 to 0.3) |
| Redness: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Swelling: Mild | 1.5 (1.3 to 1.8) | 0.5 (0.3 to 0.7) |
| Swelling: Moderate | 0.9 (0.8 to 1.2) | 0.3 (0.2 to 0.5) |
| Swelling: Severe | 0.3 (0.2 to 0.5) | 0.1 (0.0 to 0.2) |
| Swelling: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Pain at injection site: Mild | 17.5 (16.7 to 18.3) | 6.2 (5.7 to 6.8) |
| Pain at injection site: Moderate | 2.2 (1.9 to 2.5) | 0.8 (0.6 to 1.0) |
| Pain at injection site: Severe | 0.1 (0.0 to 0.2) | 0.1 (0.1 to 0.2) |
| Pain at injection site: Grade 4 | 0 (0.0 to 0.0) | 0.1 (0.0 to 0.1) |
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 | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Redness: Mild | 2.6 (2.2 to 2.9) | 0.3 (0.2 to 0.5) |
| Redness: Moderate | 2.2 (1.9 to 2.6) | 0.2 (0.1 to 0.3) |
| Redness: Severe | 0.9 (0.7 to 1.2) | 0.1 (0.0 to 0.1) |
| Redness: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Swelling: Mild | 3.2 (2.8 to 3.6) | 0.3 (0.2 to 0.5) |
| Swelling: Moderate | 3.0 (2.6 to 3.4) | 0.2 (0.1 to 0.3) |
| Swelling: Severe | 0.9 (0.7 to 1.1) | 0.1 (0.0 to 0.2) |
| Swelling: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Pain at injection site: Mild | 23.0 (22.1 to 23.9) | 4.3 (3.9 to 4.8) |
| Pain at injection site: Moderate | 4.5 (4.0 to 4.9) | 0.7 (0.5 to 0.9) |
| Pain at injection site: Severe | 0.2 (0.1 to 0.3) | 0.1 (0.0 to 0.1) |
| Pain at injection site: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
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 | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Redness: Mild | 2.6 (2.3 to 3.0) | 0.4 (0.2 to 0.5) |
| Redness: Moderate | 2.4 (2.1 to 2.8) | 0.2 (0.1 to 0.4) |
| Redness: Severe | 0.7 (0.5 to 0.9) | 0.1 (0.0 to 0.1) |
| Redness: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Swelling: Mild | 3.5 (3.1 to 3.9) | 0.3 (0.2 to 0.5) |
| Swelling: Moderate | 3.3 (2.9 to 3.7) | 0.2 (0.1 to 0.4) |
| Swelling: Severe | 0.8 (0.6 to 1.1) | 0 (0.0 to 0.0) |
| Swelling: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Pain at injection site: Mild | 21.0 (20.1 to 21.9) | 3.6 (3.2 to 4.1) |
| Pain at injection site: Moderate | 4.5 (4.0 to 5.0) | 0.8 (0.6 to 1.0) |
| Pain at injection site: Severe | 0.2 (0.1 to 0.4) | 0.1 (0.0 to 0.1) |
| Pain at injection site: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
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 | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Fever: 38.0-38.4 deg C | 0.5 (0.3 to 0.6) | 0.4 (0.3 to 0.5) |
| Fever: 38.5-38.9 deg C | 0.2 (0.1 to 0.3) | 0.2 (0.1 to 0.3) |
| Fever: 39.0-40.0 deg C | 0.2 (0.1 to 0.3) | 0.1 (0.1 to 0.2) |
| Fever: >40.0 deg C | 0.1 (0.0 to 0.2) | 0.1 (0.0 to 0.2) |
| Fatigue: Mild | 11.6 (10.9 to 12.3) | 10.2 (9.6 to 10.9) |
| Fatigue: Moderate | 10.6 (10.0 to 11.3) | 10.4 (9.7 to 11.0) |
| Fatigue: Severe | 1.1 (0.9 to 1.3) | 1.2 (1.0 to 1.5) |
| Fatigue: Grade 4 | 0.1 (0.0 to 0.1) | 0 (0.0 to 0.0) |
| Headache: Mild | 11.6 (10.9 to 12.3) | 10.1 (9.4 to 10.7) |
| Headache: Moderate | 5.8 (5.3 to 6.3) | 5.4 (4.9 to 5.9) |
| Headache: Severe | 0.5 (0.4 to 0.7) | 0.6 (0.5 to 0.8) |
| Headache: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Vomiting: Mild | 1.1 (0.8 to 1.3) | 0.7 (0.5 to 0.9) |
| Vomiting: Moderate | 0.3 (0.2 to 0.4) | 0.2 (0.1 to 0.3) |
| Vomiting: Severe | 0.1 (0.0 to 0.1) | 0.1 (0.0 to 0.1) |
| Vomiting: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| New or worsening muscle pain: Mild | 5.2 (4.7 to 5.7) | 3.9 (3.5 to 4.3) |
| New or worsening muscle pain: Moderate | 5.7 (5.2 to 6.2) | 5.6 (5.1 to 6.1) |
| New or worsening muscle pain: Severe | 0.6 (0.4 to 0.8) | 0.6 (0.5 to 0.8) |
| New or worsening muscle pain: Grade 4 | 0.1 (0.0 to 0.1) | 0 (0.0 to 0.0) |
| New or worsening joint pain: Mild | 4.0 (3.6 to 4.5) | 3.3 (2.9 to 3.7) |
| New or worsening joint pain: Moderate | 5.2 (4.7 to 5.7) | 5.0 (4.5 to 5.5) |
| New or worsening joint pain: Severe | 0.5 (0.4 to 0.7) | 0.5 (0.3 to 0.6) |
| New or worsening joint pain: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
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 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 | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Fever: 38.0-38.4 deg C | 0.4 (0.3 to 0.6) | 0.4 (0.3 to 0.6) |
| Fever: 38.5-38.9 deg C | 0.2 (0.1 to 0.3) | 0.1 (0.0 to 0.2) |
| Fever: 39.0-40.0 deg C | 0.1 (0.0 to 0.2) | 0.2 (0.1 to 0.3) |
| Fever: >40.0 deg C | 0.1 (0.0 to 0.1) | 0.1 (0.0 to 0.1) |
| Fatigue: Mild | 10.2 (9.6 to 10.9) | 7.8 (7.2 to 8.4) |
| Fatigue: Moderate | 9.4 (8.7 to 10.0) | 9.0 (8.4 to 9.6) |
| Fatigue: Severe | 1.0 (0.8 to 1.2) | 1.0 (0.8 to 1.2) |
| Fatigue: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Headache: Mild | 10.1 (9.4 to 10.8) | 8.3 (7.7 to 9.0) |
| Headache: Moderate | 5.1 (4.6 to 5.6) | 5.5 (5.0 to 6.1) |
| Headache: Severe | 0.5 (0.4 to 0.7) | 0.4 (0.3 to 0.6) |
| Headache: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Vomiting: Mild | 0.8 (0.6 to 1.0) | 0.7 (0.5 to 0.9) |
| Vomiting: Moderate | 0.2 (0.1 to 0.4) | 0.2 (0.1 to 0.3) |
| Vomiting: Severe | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Vomiting: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| New or worsening muscle pain: Mild | 4.8 (4.3 to 5.3) | 3.2 (2.9 to 3.6) |
| New or worsening muscle pain: Moderate | 5.1 (4.6 to 5.6) | 4.2 (3.8 to 4.7) |
| New or worsening muscle pain: Severe | 0.5 (0.4 to 0.7) | 0.6 (0.4 to 0.8) |
| New or worsening muscle pain: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| New or worsening joint pain: Mild | 3.8 (3.4 to 4.2) | 2.9 (2.6 to 3.3) |
| New or worsening joint pain: Moderate | 4.6 (4.1 to 5.0) | 3.9 (3.5 to 4.4) |
| New or worsening joint pain: Severe | 0.4 (0.3 to 0.6) | 0.5 (0.3 to 0.6) |
| New or worsening joint pain: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
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 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 | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Fever: 38.0-38.4 deg C | 0.4 (0.3 to 0.6) | 0.2 (0.1 to 0.4) |
| Fever: 38.5-38.9 deg C | 0.1 (0.1 to 0.2) | 0.1 (0.0 to 0.2) |
| Fever: 39.0-40.0 deg C | 0.1 (0.1 to 0.2) | 0.1 (0.0 to 0.2) |
| Fever: >40.0 deg C | 0.1 (0.0 to 0.1) | 0.1 (0.0 to 0.1) |
| Fatigue: Mild | 9.2 (8.6 to 9.9) | 7.0 (6.4 to 7.6) |
| Fatigue: Moderate | 9.4 (8.7 to 10.0) | 8.0 (7.4 to 8.6) |
| Fatigue: Severe | 0.8 (0.6 to 1.0) | 0.8 (0.6 to 1.0) |
| Fatigue: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Headache: Mild | 8.4 (7.8 to 9.0) | 7.9 (7.3 to 8.5) |
| Headache: Moderate | 5.7 (5.1 to 6.2) | 4.7 (4.2 to 5.2) |
| Headache: Severe | 0.3 (0.2 to 0.5) | 0.5 (0.3 to 0.6) |
| Headache: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Vomiting: Mild | 0.6 (0.5 to 0.8) | 0.5 (0.4 to 0.7) |
| Vomiting: Moderate | 0.1 (0.0 to 0.2) | 0.2 (0.1 to 0.3) |
| Vomiting: Severe | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| Vomiting: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| New or worsening muscle pain: Mild | 4.0 (3.5 to 4.4) | 2.5 (2.2 to 2.9) |
| New or worsening muscle pain: Moderate | 4.8 (4.3 to 5.3) | 4.1 (3.6 to 4.6) |
| New or worsening muscle pain: Severe | 0.5 (0.3 to 0.7) | 0.5 (0.3 to 0.7) |
| New or worsening muscle pain: Grade 4 | 0 (0.0 to 0.0) | 0 (0.0 to 0.0) |
| New or worsening joint pain: Mild | 3.0 (2.6 to 3.4) | 2.5 (2.2 to 2.9) |
| New or worsening joint pain: Moderate | 4.4 (3.9 to 4.8) | 3.6 (3.2 to 4.0) |
| New or worsening joint pain: Severe | 0.4 (0.3 to 0.6) | 0.4 (0.3 to 0.5) |
| New or worsening joint pain: Grade 4 | 0.1 (0.0 to 0.1) | 0 (0.0 to 0.0) |
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).
| Participants | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Any AEs | 4161 | 4050 |
| Non-Serious AEs | 3913 | 3791 |
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.
| Participants | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of Participants Reporting Serious Adverse Events (SAEs) | 719 | 722 |
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.
| Episodes | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of All Episodes of CDI (Definition 1 and 2) After Dose 3 | 28 | 32 |
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.
| Days | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Time to Resolution for Participants With First Primary Episodes of CDI (Definition 1) After Dose 3 | 1.0 (1 to 18) | 4.0 (1 to 183) |
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 | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Proportion of Participants Who Required Medical Attention During First Primary Episode of CDI (Definition 1) After Dose 3 | 0 | 0.440 |
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.
| Participants | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 3 | 5 | 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.
| Episodes | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of All Episodes of CDI (Definition 1 and 2) After Dose 2 | 37 | 44 |
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.
| Participants | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of Participants With Recurrent Episodes of CDI (Definition 2) After Dose 2 | 6 | 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.
| Episodes | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of First Primary Episode of CDI (Definition 1) After Dose 2 and Before Dose 3 | 7 | 8 |
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.
| Participants | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Number of Participants With Recurrent Episode of CDI (Definition 2) After Dose 2 and Before Dose 3 | 1 | 0 |
Collected over 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). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Clostridium Difficile Vaccine | 369/8,722 (4.2%) | 719/8,722 (8.2%) | 5,702/8,722 (65.4%) |
| Placebo | 362/8,718 (4.2%) | 722/8,718 (8.3%) | 4,314/8,718 (49.5%) |
| Event | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 33/8722 | 43/8718 |
| PneumoniaInfections and infestations | 38/8722 | 39/8718 |
| Chest painGeneral disorders | 25/8722 | 32/8718 |
| CellulitisInfections and infestations | 23/8722 | 18/8718 |
| Acute myocardial infarctionCardiac disorders | 20/8722 | 8/8718 |
| Acute kidney injuryRenal and urinary disorders | 9/8722 | 18/8718 |
| OsteoarthritisMusculoskeletal and connective tissue disorders | 18/8722 | 15/8718 |
| Cardiac failure congestiveCardiac disorders | 14/8722 | 17/8718 |
| SepsisInfections and infestations | 16/8722 | 16/8718 |
| Atrial fibrillationCardiac disorders | 12/8722 | 15/8718 |
| Event | Clostridium Difficile Vaccine | Placebo |
|---|---|---|
| Injection site pain (PAIN)General disorders | 3596/8722 | 1056/8718 |
| Fatigue (FATIGUE)General disorders | 3240/8722 | 2820/8718 |
| Headache (HEADACHE)Nervous system disorders | 2615/8722 | 2323/8718 |
| Injection site erythema (REDNESS)General disorders | 1879/8722 | 653/8718 |
| Myalgia (MUSCLE PAIN)Musculoskeletal and connective tissue disorders | 1856/8722 | 1487/8718 |
| Injection site swelling (SWELLING)General disorders | 1846/8722 | 414/8718 |
| Arthralgia (JOINT PAIN)Musculoskeletal and connective tissue disorders | 1583/8722 | 1354/8718 |
Safety analysis population included all participants who received at least 1 dose of the investigational product.
| Age, Continuous(Years) | Clostridium Difficile Vaccine | Placebo | Total |
|---|---|---|---|
| Mean | 68.0 ± 7.5 | 68.1 ± 7.5 | 68.0 ± 7.5 |
| Sex: Female, Male(Participants) | Clostridium Difficile Vaccine | Placebo | Total |
|---|---|---|---|
| Female | 4472 | 4501 | 8973 |
| Male | 4250 | 4217 | 8467 |
| Ethnicity (NIH/OMB)(Participants) | Clostridium Difficile Vaccine | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 1119 | 1143 | 2262 |
| Not Hispanic or Latino | 7546 | 7515 | 15061 |
| Unknown or Not Reported | 57 | 60 | 117 |
| Race (NIH/OMB)(Participants) | Clostridium Difficile Vaccine | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 53 | 54 | 107 |
| Asian | 754 | 725 | 1479 |
| Native Hawaiian or Other Pacific Islander | 20 | 14 | 34 |
| Black or African American | 663 | 666 | 1329 |
| White | 6891 | 6922 | 13813 |
| More than one race | 327 | 322 | 649 |
| Unknown or Not Reported | 14 | 15 | 29 |
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Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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