Clostridium Infections
Conditions
Keywords
Clostridium difficile
Brief summary
The purpose of this study is to determine the safety and tolerability of a modified C. difficile vaccine at 3 dose levels compared with a placebo control administered via intramuscular injection in healthy adults aged 18-55 years of age.
Detailed description
Clostridium difficile is the leading infectious cause of nosocomial diarrhea in developed countries. Hospital outbreaks of Clostridium difficile-associated diarrhea (CDAD) are associated with substantial patient morbidity and mortality. Conventional therapy with antibiotics often results in secondary infection with resistant organisms or clinical relapse after discontinuation of the antimicrobial course. New strategies are needed to limit the impact of this opportunistic pathogen. Considerable evidence exists that immunity against C. difficile toxins may be effective in controlling CDAD. 48 subjects will be enrolled to receive one of three dose levels of modified C difficile vaccine or placebo administered on a 3-dose schedule. The study consists of a 30-day screening period, a 70-day treatment period, one follow-up phone interview 2 months after the last vaccination, and one follow-up clinic visit 6 months after the last vaccination.
Interventions
BIOLOGICALPlacebo (vaccine diluent)
0.5 mL, intramuscular (IM) on Days 0, 28, and 56, respectively.
BIOLOGICALClostridium difficile vaccine
0.5 mL, intramuscular on Days 0, 28, and 56, respectively.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Adult males or females, 18-55 years (inclusive) * In good general health * Clinical lab tests within normal range * Non-pregnant female subjects * Able and willing to participate for duration of study and must not participate in any other experimental study for at least 60 days after receiving the last dose of study vaccine
Exclusion criteria
* Evidence of C. difficile infection * Evidence of any previous antibiotic-associated diarrhea * Active or inactive inflammatory bowel disease, irritable colon syndrome, chronic abdominal pain or other chronic diarrhea * History of malignancy within 5 years * History of anaphylaxis, asthma or severe vaccine or severe allergic drug reaction * Known or suspected history of immunodeficiency; * Active or inactive immune-mediated or inflammatory disease; * Pregnant or lactating female subjects; * History of drug or alcohol abuse disorders; * Serology positive for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) * Receipt of antibiotic therapy or an investigational drug within prior 30 days * Blood or organ donation within prior 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Day 0 and up to 7 days post each vaccination |
| Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Day 0 to up to 70 days post-first vaccination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Days 28, 56, 70, and 236 Post First Vaccination | Seroconversion was defined as a ≥4-fold increase in antibody levels from Baseline. For values below the limit of quantification (LLQ) for the assay, the LLQ was used. Serum anti-toxin IgG levels were determined by enzyme linked immunosorbent assay (ELISA). |
Participant flow
Recruitment details
Participants were enrolled from 13 July 2005 to 27 July 2005 in 2 medical centers in the US.
Pre-assignment details
A total of 50 participants who met the inclusion, but no exclusion criteria were enrolled and vaccinated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Group Participants who received 3 doses of vaccine diluent (placebo) on Days 0, 28, and 56. | 13 |
| Low Dose Vaccine Group Participants who received 3 doses of vaccine containing 2 μg C. difficile toxoid on Days 0, 28, and 56. | 13 |
| Medium Dose Vaccine Group Participants who received 3 doses of vaccine containing 10 μg C. difficile toxoid on Days 0, 28, and 56. | 12 |
| High Dose Vaccine Group Participants who received 3 doses of vaccine containing 50 μg C. difficile toxoid on Days 0, 28, and 56. | 12 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Low Dose Vaccine Group | Medium Dose Vaccine Group | Placebo Group | High Dose Vaccine Group | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 12 Participants | 13 Participants | 12 Participants | 50 Participants |
| Age Continuous | 30.8 Years STANDARD_DEVIATION 10.26 | 30.4 Years STANDARD_DEVIATION 9.78 | 33.6 Years STANDARD_DEVIATION 12.49 | 32.6 Years STANDARD_DEVIATION 9.07 | 31.9 Years STANDARD_DEVIATION 10.28 |
| Region of Enrollment United States | 13 participants | 12 participants | 13 participants | 12 participants | 50 participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 10 Participants | 9 Participants | 33 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 3 Participants | 3 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 13 / 13 | 12 / 12 | 12 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine.
Time frame: Day 0 and up to 7 days post each vaccination
Population: Safety assessments were on the safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 0 | 2 Participants |
| Placebo Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 28 | 0 Participants |
| Placebo Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 56 | 2 Participants |
| Placebo Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 0 | 0 Participants |
| Placebo Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 28 | 0 Participants |
| Placebo Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 56 | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 56 | 2 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 0 | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 0 | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 56 | 2 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 28 | 3 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 28 | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 28 | 3 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 56 | 3 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 0 | 3 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 56 | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 28 | 0 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 0 | 1 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 28 | 2 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 56 | 1 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 28 | 2 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Tenderness Day 0 | 1 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 0 | 2 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Solicited Injection Site Erythema and Tenderness Post-vaccination With Either One of Three Formulations of Clostridium Difficile Vaccines or a Placebo Vaccine. | Erythema Day 56 | 3 Participants |
Primary
Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine.
Time frame: Day 0 to up to 70 days post-first vaccination
Population: Safety assessments were on the safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Upper respiratory tract infection | 2 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood potassium increased | 3 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Abdominal pain | 1 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Eosinophil count increased | 1 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site paraesthesia | 2 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site pain | 8 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Protein urine present | 2 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site erythema | 2 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Diarrhoea | 3 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Red blood cells urine positive | 2 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site warmth | 1 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site induration | 0 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site swelling | 1 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Myalgia | 2 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Fatigue | 2 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site pruritus | 0 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cells urine positive | 3 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cell count decreased | 0 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood potassium increased | 3 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Pain in extremity | 5 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Sensation of heaviness | 0 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site irritation | 2 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood urea increased | 0 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Sinus headache | 0 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Headache | 4 Participants |
| Placebo Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cell count increased | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Sinus headache | 2 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cells urine positive | 1 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood potassium increased | 1 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site swelling | 2 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site pruritus | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Fatigue | 1 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site paraesthesia | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Abdominal pain | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Protein urine present | 6 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site irritation | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site pain | 11 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood urea increased | 1 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cell count increased | 2 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cell count decreased | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site erythema | 6 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Sensation of heaviness | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Red blood cells urine positive | 5 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Upper respiratory tract infection | 3 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Headache | 4 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site warmth | 1 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood potassium increased | 1 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Diarrhoea | 2 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site induration | 1 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Pain in extremity | 0 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Eosinophil count increased | 2 Participants |
| Low Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Myalgia | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cells urine positive | 3 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site swelling | 3 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Sensation of heaviness | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site induration | 4 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Abdominal pain | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site warmth | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Fatigue | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Myalgia | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site pruritus | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cell count decreased | 2 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood potassium increased | 0 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site irritation | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Sinus headache | 0 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cell count increased | 0 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood potassium increased | 0 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site paraesthesia | 0 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site pain | 11 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site erythema | 5 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Red blood cells urine positive | 6 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Protein urine present | 4 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Eosinophil count increased | 5 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Headache | 3 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Upper respiratory tract infection | 2 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Pain in extremity | 1 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Diarrhoea | 0 Participants |
| Medium Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood urea increased | 4 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cell count increased | 0 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood urea increased | 2 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Eosinophil count increased | 3 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Sinus headache | 0 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site irritation | 0 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Diarrhoea | 3 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Headache | 0 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood potassium increased | 0 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cell count decreased | 2 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Sensation of heaviness | 2 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Upper respiratory tract infection | 3 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site pruritus | 3 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Myalgia | 1 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Fatigue | 2 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | White blood cells urine positive | 3 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Pain in extremity | 3 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site warmth | 3 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site swelling | 3 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site erythema | 6 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Abdominal pain | 4 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Red blood cells urine positive | 5 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site pain | 12 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site paraesthesia | 0 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Injection site induration | 2 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Protein urine present | 5 Participants |
| High Dose Vaccine Group | Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Blood potassium increased | 0 Participants |
Secondary
Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine.
Seroconversion was defined as a ≥4-fold increase in antibody levels from Baseline. For values below the limit of quantification (LLQ) for the assay, the LLQ was used. Serum anti-toxin IgG levels were determined by enzyme linked immunosorbent assay (ELISA).
Time frame: Days 28, 56, 70, and 236 Post First Vaccination
Population: Serum anti-toxin levels were assessed in the Fully Evaluable (Per-Protocol) Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 28 | 0 Participants |
| Placebo Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 28 | 0 Participants |
| Placebo Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 56 | 0 Participants |
| Placebo Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 56 | 0 Participants |
| Placebo Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 236 | 0 Participants |
| Placebo Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 70 | 0 Participants |
| Placebo Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 70 | 0 Participants |
| Placebo Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 236 | 0 Participants |
| Low Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 28 | 6 Participants |
| Low Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 56 | 3 Participants |
| Low Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 70 | 6 Participants |
| Low Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 28 | 2 Participants |
| Low Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 236 | 12 Participants |
| Low Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 236 | 2 Participants |
| Low Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 70 | 13 Participants |
| Low Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 56 | 13 Participants |
| Medium Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 236 | 12 Participants |
| Medium Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 28 | 5 Participants |
| Medium Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 28 | 5 Participants |
| Medium Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 56 | 12 Participants |
| Medium Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 70 | 12 Participants |
| Medium Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 56 | 6 Participants |
| Medium Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 70 | 7 Participants |
| Medium Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 236 | 4 Participants |
| High Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 70 | 11 Participants |
| High Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 56 | 11 Participants |
| High Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 236 | 6 Participants |
| High Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 70 | 8 Participants |
| High Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 28 | 7 Participants |
| High Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 236 | 10 Participants |
| High Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin A Day 28 | 10 Participants |
| High Dose Vaccine Group | Number of Participants With Seroconversion for Toxin A and Toxin B Post-vaccination With Either One of Three Formulations of the Clostridium Difficile Vaccine or a Placebo Vaccine. | Toxin B Day 56 | 7 Participants |