Clostridium Difficile Infection Recurrence
Conditions
Keywords
Clostridium Difficile Infection, CP101, Crestovo, FMT, CDI, C. difficile, C. diff, Recurrent Clostridium Difficile Infection, Recurrent C. diff, Recurrent CDI, Finch, Fecal transplant, Fecal microbiota transplant, rCDI, Finch Therapeutics
Brief summary
Subjects with recurrent C. difficile infection will receive an oral dose of CP101 capsules one time in Treatment Group I or matching placebo one time in Treatment Group II. The purpose of this study is to demonstrate the safety and effectiveness of CP101 to prevent recurrence of C. difficile. Subjects with confirmed C. difficile recurrence within 8 weeks after administration of study drug (CP101 or placebo) may be eligible to enroll in the open-label extension study (CP101-CDI-E02) and will receive CP101.
Detailed description
This is a Multicenter, Double-Blind, Parallel-Arm, Placebo-Controlled, Phase 2 Study of the Efficacy, Safety, and Tolerability of Oral Full-Spectrum MicrobiotaTM (CP101) in Subjects with Recurrence of Clostridium difficile Infection (CDI).
Interventions
Orally administered donor derived microbiota
DRUGPlacebo
Placebo for CP101
Sponsors
Finch Research and Development LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent * Men or women 18 years of age or older * Current diagnosis of a recurrence of non-severe, non-complicated CDI * Subject has a clinical response to standard-of-care CDI antibiotics for the most recent CDI episode
Exclusion criteria
* Pregnant, breast-feeding, or considering becoming pregnant during the study * Prior history, evidence, or diagnosis of inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) * Any prior diagnosis of diarrhea-predominant irritable bowel syndrome * Systemic chemotherapy or radiation for the treatment of cancer during the 60 days prior to consent or planned during the 8 weeks following Randomization * Prior fecal transplant for any condition, regardless of route of administration in the last year or plans to undergo during the study * Major intra-abdominal surgery within the past 60 days prior to Screening * History of total colectomy/ileostomy or bariatric surgery * Admitted to, or expected to be admitted to an intensive care unit for any medical reason. Note: Residents of long term care facilities are eligible study entry * Planned hospitalization or invasive surgery during the study * Severe acute illness unrelated to CDI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Absence of Recurrence Through Week 8 Based on Adjudication | Week 8 | Defined in the protocol as sustained clinical cure |
| Number of Participants With Occurrence of Treatment Emergent Adverse Events | Week 8 | Mapped to System Organ Class. Any adverse event (AE) reported that occurs during or post the administration of IP is defined as a Treatment Emergent AE (TEAE) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Recurrent CDI Episode During the Study | Week 8 | The number of days between IP administration and the first C. Difficile recurrence |
| Number of Participants With Absence of Recurrence Through Week 24 Based on Adjudication | Week 24 | Defined in the protocol as sustained clinical cure |
| Number of Participants With Recurrence by Ribosomal NAP1/BI/027 C. Difficile Subtype | Up to Week 8 | NAP1 is the North American Pulse-field C. difficile subtype. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CP101 Full Spectrum Microbiota Capsule
Full Spectrum Microbiota: Orally administered donor derived microbiota | 102 |
| Placebo Matching Placebo Capsule
Placebo: Placebo for CP101 | 96 |
| Total | 198 |
Baseline characteristics
| Characteristic | Total | CP101 | Placebo |
|---|---|---|---|
| Age, Continuous | 66.2 Years STANDARD_DEVIATION 15.84 | 65.9 Years STANDARD_DEVIATION 17.26 | 66.5 Years STANDARD_DEVIATION 14.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 186 Participants | 96 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 2 Participants | 2 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 | 182 Participants | 93 Participants | 89 Participants |
| Region of Enrollment North America | 198 participants | 102 participants | 96 participants |
| Sex: Female, Male Female | 134 Participants | 69 Participants | 65 Participants |
| Sex: Female, Male Male | 64 Participants | 33 Participants | 31 Participants |
| Total Number of C. difficile Infection (CDI) Episodes in Previous 12 Months 1 | 1 Participants | 1 Participants | 0 Participants |
| Total Number of C. difficile Infection (CDI) Episodes in Previous 12 Months 2 | 66 Participants | 37 Participants | 29 Participants |
| Total Number of C. difficile Infection (CDI) Episodes in Previous 12 Months 3 | 94 Participants | 46 Participants | 48 Participants |
| Total Number of C. difficile Infection (CDI) Episodes in Previous 12 Months >3 | 37 Participants | 18 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 104 | 2 / 99 |
| other Total, other adverse events | 97 / 104 | 92 / 99 |
| serious Total, serious adverse events | 16 / 104 | 13 / 99 |
Outcome results
Primary
Number of Participants With Absence of Recurrence Through Week 8 Based on Adjudication
Defined in the protocol as sustained clinical cure
Time frame: Week 8
Population: mITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CP101 | Number of Participants With Absence of Recurrence Through Week 8 Based on Adjudication | 76 Participants |
| Placebo | Number of Participants With Absence of Recurrence Through Week 8 Based on Adjudication | 59 Participants |
p-value: 0.0488Chi-squared
Primary
Number of Participants With Occurrence of Treatment Emergent Adverse Events
Mapped to System Organ Class. Any adverse event (AE) reported that occurs during or post the administration of IP is defined as a Treatment Emergent AE (TEAE)
Time frame: Week 8
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CP101 | Number of Participants With Occurrence of Treatment Emergent Adverse Events | 96 Participants |
| Placebo | Number of Participants With Occurrence of Treatment Emergent Adverse Events | 88 Participants |
Secondary
Number of Participants With Absence of Recurrence Through Week 24 Based on Adjudication
Defined in the protocol as sustained clinical cure
Time frame: Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CP101 | Number of Participants With Absence of Recurrence Through Week 24 Based on Adjudication | 75 Participants |
| Placebo | Number of Participants With Absence of Recurrence Through Week 24 Based on Adjudication | 57 Participants |
p-value: 0.0347Chi-squared
Secondary
Number of Participants With Recurrence by Ribosomal NAP1/BI/027 C. Difficile Subtype
NAP1 is the North American Pulse-field C. difficile subtype.
Time frame: Up to Week 8
Population: Analysis population only included participants with a CDI recurrence up to week 8. Two of the recurrences in the primary efficacy analyses were imputed, therefore only 24 samples were available for this analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CP101 | Number of Participants With Recurrence by Ribosomal NAP1/BI/027 C. Difficile Subtype | Ribosomal NAP1/BI/027 Positive at Recurrence | 6 Participants |
| CP101 | Number of Participants With Recurrence by Ribosomal NAP1/BI/027 C. Difficile Subtype | Ribosomal NAP1/BI/027 Negative or Unknown at Recurrence | 18 Participants |
| Placebo | Number of Participants With Recurrence by Ribosomal NAP1/BI/027 C. Difficile Subtype | Ribosomal NAP1/BI/027 Positive at Recurrence | 7 Participants |
| Placebo | Number of Participants With Recurrence by Ribosomal NAP1/BI/027 C. Difficile Subtype | Ribosomal NAP1/BI/027 Negative or Unknown at Recurrence | 30 Participants |
Secondary
Time to First Recurrent CDI Episode During the Study
The number of days between IP administration and the first C. Difficile recurrence
Time frame: Week 8
Population: mITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CP101 | Time to First Recurrent CDI Episode During the Study | 17.1 Days | Standard Deviation 10.95 |
| Placebo | Time to First Recurrent CDI Episode During the Study | 11.3 Days | Standard Deviation 6.92 |