Clostridium Difficile, Clostridium Infections
Conditions
Brief summary
A Phase 2b Parallel-Group, Double-Blind, Placebo-Controlled, Multicenter Study of SYN-004 Compared to Placebo for the Prevention of Clostridium difficile Infection (CDI) in Hospitalized Patients receiving IV ceftriaxone with a Diagnosis of a Lower Respiratory Tract Infection (LRTI).
Detailed description
This is a Phase 2b, randomized, double-blind, placebo controlled, parallel-group, multi-center proof-of-concept study to assess the potential of SYN-004 in the prevention of CDI and the unwanted side effects of IV antibiotic treatment in at risk patients who are hospitalized for LRTI and receiving IV ceftriaxone alone or in combination with a macrolide. Subjects will be 50 years or older. The entire duration of the study may be up to 59 days. All patients will be evaluated for the occurrence of CDI and AAD by testing according to local diagnostic standards and monitoring for diarrhea (3 or more unformed stools per 24 hour period).
Interventions
DRUGSYN-004
DRUGPlacebo
Sponsors
Theriva Biologics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Expected minimum hospital stay of 5 days * Expected ≥5 day course of intravenous (IV) ceftriaxone alone or in combination with a macrolide * Clinical diagnosis of moderate to severe lower respiratory tract infection consisting of signs and symptoms of a lower respiratory tract infection and Pneumonia Severity Index (PSI/PORT) score for CAP of 90-130, inclusive. Evidence of a new or progressive infiltrate on chest x-ray is recommended.
Exclusion criteria
* Presence of a diarrheal illness within 72 hours prior to randomization * Current treatment for CDAD or ongoing active CDI, as evidenced by clinical signs of diarrhea along with the presence of toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool * Number of previous CDAD episodes \>1 within 12 weeks of randomization and no C. difficile infection (CDI) within 4 weeks of randomization * Use of antibiotics within 1 month of start of study drug except for the current illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Clostridium Difficile Infection at 4- Weeks of Follow-up. | Day 1 to the 4 week Follow-up Visit. | Percentage of subjects with CDI, based on the protocol definition of CDI (defined as 3 or more unformed stools per 24 hour period and a stool sample being positive for C. difficile toxin A and/or B \[or their respective genes, tcdA and/or tcdB\], based on the clinical site local laboratory results) from Day 1 to the 4-week Follow-up Visit in the SYN-004 treatment group compared to the placebo group, imputing early termination without CDI as not being treatment failures. |
Countries
Bulgaria, Canada, Hungary, Poland, Romania, Serbia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SYN-004 SYN-004 150 mg | 206 |
| Placebo Matching Placebo | 206 |
| Total | 412 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 15 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Other reason - not specified | 2 | 1 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Use of non-permitted concurrent therapy | 1 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 8 |
Baseline characteristics
| Characteristic | SYN-004 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 9.37 | 69.7 years STANDARD_DEVIATION 9.37 | 69.2 years STANDARD_DEVIATION 9.37 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 206 Participants | 205 Participants | 411 Participants |
| Region of Enrollment Europe | 203 Participants | 201 Participants | 404 Participants |
| Region of Enrollment North America | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 73 Participants | 80 Participants | 153 Participants |
| Sex: Female, Male Male | 133 Participants | 126 Participants | 259 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 206 | 5 / 206 |
| other Total, other adverse events | 59 / 206 | 59 / 206 |
| serious Total, serious adverse events | 33 / 206 | 21 / 206 |
Outcome results
Primary
Percentage of Patients With Clostridium Difficile Infection at 4- Weeks of Follow-up.
Percentage of subjects with CDI, based on the protocol definition of CDI (defined as 3 or more unformed stools per 24 hour period and a stool sample being positive for C. difficile toxin A and/or B \[or their respective genes, tcdA and/or tcdB\], based on the clinical site local laboratory results) from Day 1 to the 4-week Follow-up Visit in the SYN-004 treatment group compared to the placebo group, imputing early termination without CDI as not being treatment failures.
Time frame: Day 1 to the 4 week Follow-up Visit.
Population: The Modified Intent-to-Treat (mITT) analysis set included randomized subjects who received at least 1dose of study drug. Number of subjects with CDI, imputing early termination without CDI as not being treatment failures.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SYN-004 | Percentage of Patients With Clostridium Difficile Infection at 4- Weeks of Follow-up. | 2 Participants |
| Placebo | Percentage of Patients With Clostridium Difficile Infection at 4- Weeks of Follow-up. | 7 Participants |
Comparison: The Modified Intent-to-Treat (mITT) analysis set included randomized subjects who received at least 1 dose of study drug. Number of subjects with CDI, imputing early termination without CDI as not being treatment failures.p-value: 0.04595% CI: [-35.9, 94]z-test