Clostridium Difficile Infection
Conditions
Keywords
Clostridium difficile, C diff, CDI, CDAD, Fecal transplant, Fecal Microbiota transplant, diarrhea, FMT, microbiota restoration therapy, microbiota suspension, fecal bacteriotherapy, C diff diarrhea
Brief summary
This study will evaluate efficacy and safety information about RBX2660 for the treatment of recurrent Clostridium difficile infection (CDI), and will compare the efficacy of one treatment with RBX2660 versus antibiotic-treated historical controls. Enrolled subjects will receive one treatment consisting of two doses of RBX2660 (microbiota suspension).
Detailed description
This is a prospective, multicenter, open-label study assessing the efficacy and safety of RBX2660 as an adjunct to antibiotics for the treatment of recurrent CDI. Efficacy of RBX2660, measured by the recurrence-free rate of CDI diarrhea without the need for retreatment with C. difficile anti-infective therapy or fecal transplant through 56 days after completion of study treatment with RBX2660, will be evaluated by comparing the recurrence-free rate observed in the study population to the recurrence-free rate identified from antibiotic-treated historical controls. Patients who have had either a) at least two recurrences after a primary episode (i.e., at least three episodes) and have completed at least two rounds of standard-of-care oral antibiotics or b) have had at least two episodes of severe CDI resulting in hospitalization may be eligible to participate in the study. Study visits are 1- and 8-weeks after treatment with additional follow-up assessments at 3,6,12, and 24 months post treatment.
Interventions
BIOLOGICALRBX2660
suspension of intestinal microbes
Standard of Care Antibiotics
Sponsors
Rebiotix Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years old. * Medical record documentation of recurrent CDI including a positive C. difficile test within 60 days prior to enrollment and either: a) at least two recurrences after a primary episode and has completed at least two rounds of standard-of-care oral antibiotic therapy or b) has had at least two episodes of severe CDI resulting in hospitalization. * Documented history that the subject's recurrent CDI is controlled while on antibiotics even if the subject is not currently on antibiotics. * A positive stool test for the presence of C. difficile within 60 days prior to enrollment
Exclusion criteria
* A known history of continued CDI diarrhea despite being on a course of antibiotics prescribed for CDI treatment. * Requires continuous antibiotic therapy for a condition other than CDI. * Previous successful (resolution of CDI diarrhea) fecal transplant for recurrent CDI \< 6 months prior to study enrollment. * Previous unsuccessful (recurrent CDI diarrhea was unresolved) fecal transplant. * Previous treatment with RBX2660. * Diagnosis of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis. * Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria. * History of chronic diarrhea. * History of celiac disease. * Disease symptoms caused by a confirmed intestinal pathogen other than C. difficile. * Colostomy. * Planned surgery requiring perioperative antibiotics within 3 months of study enrollment. * Life expectancy of \< 12 months. * Compromised immune system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks | 8 weeks after treatment | Participants were evaluated 8 weeks after study treatment to assess efficacy of RBX2660. Efficacy was assessed as the absence of CDI diarrhea without the need for retreatment with C. difficile anti-infective therapy or fecal transplant through 56 days after completion of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life (SF-36) | Baseline | The Short Form - 36 quality of life questionnaire (SF-36) is a tool used to identify changes to quality of life following study treatment. It consists of a series of 36 questions relating to Mental and Physical health, summarized by a Physical Component Score (PCS) and Mental Component Score (MCS), respectively. Several sub-scales exist for each of the larger components; PCS includes PF, RP, BP, and GH while, MCS includes VT, SF, RE, and MH \[All abbreviations are defined in table\]. All Sub-Scale and Component Scores were calculated using Quality Metric Health Outcomes Scoring Software v4.5. The range of all scores is normalized from 0 (worst) to 100 (best). The data is presented for mean scores at baseline and 8-weeks post-treatment. |
| Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | 24 months | Major complications of rCDI, defined as death, septic shock, toxic megacolon, colonic perforation, emergency colectomy, or ICU admission) were collected and reported as a safety-related endpoint. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RBX2660 Open-label RBX2660 (microbiota suspension)
RBX2660: suspension of intestinal microbes | 149 |
| Historical Control Antibiotics Retrospective Historical Control with standard of care
Standard of Care Antibiotics: Standard of Care Antibiotics | 104 |
| Total | 253 |
Baseline characteristics
| Characteristic | RBX2660 Open-label | Historical Control Antibiotics | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 87 Participants | 64 Participants | 151 Participants |
| Age, Categorical Between 18 and 65 years | 62 Participants | 40 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants | 44 Participants | 186 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 55 Participants | 58 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 16 Participants | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 45 Participants | 48 Participants |
| Race (NIH/OMB) White | 136 Participants | 40 Participants | 176 Participants |
| Sex: Female, Male Female | 95 Participants | 71 Participants | 166 Participants |
| Sex: Female, Male Male | 54 Participants | 33 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 149 | 5 / 104 |
| other Total, other adverse events | 118 / 149 | 62 / 104 |
| serious Total, serious adverse events | 52 / 149 | 30 / 104 |
Outcome results
Primary
Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks
Participants were evaluated 8 weeks after study treatment to assess efficacy of RBX2660. Efficacy was assessed as the absence of CDI diarrhea without the need for retreatment with C. difficile anti-infective therapy or fecal transplant through 56 days after completion of study treatment.
Time frame: 8 weeks after treatment
Population: Evaluable Population - All participants evaluable for a treatment outcome through 56 days after completion of treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RBX2660 Open-label | Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks | Treatment Success | 112 Participants |
| RBX2660 Open-label | Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks | Treatment Failure | 30 Participants |
| Historical Control Antibiotics | Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks | Treatment Success | 23 Participants |
| Historical Control Antibiotics | Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks | Treatment Failure | 52 Participants |
Secondary
Number of Participants With Major Complications of rCDI From Baseline Through 24 Months
Major complications of rCDI, defined as death, septic shock, toxic megacolon, colonic perforation, emergency colectomy, or ICU admission) were collected and reported as a safety-related endpoint.
Time frame: 24 months
Population: Full Analysis Set- Defined as participants who received at least one dose of RBX2660 or was in the Historical Control Arm
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RBX2660 Open-label | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Septic Shock | 2 Participants |
| RBX2660 Open-label | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Colonic Perforations | 0 Participants |
| RBX2660 Open-label | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Death | 1 Participants |
| RBX2660 Open-label | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Emergency Colectomy | 0 Participants |
| RBX2660 Open-label | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Toxic Megacolon | 0 Participants |
| RBX2660 Open-label | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | ICU Admission | 2 Participants |
| RBX2660 Open-label | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | At least one complication of rCDI | 3 Participants |
| Historical Control Antibiotics | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | ICU Admission | 0 Participants |
| Historical Control Antibiotics | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | At least one complication of rCDI | 2 Participants |
| Historical Control Antibiotics | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Death | 0 Participants |
| Historical Control Antibiotics | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Septic Shock | 1 Participants |
| Historical Control Antibiotics | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Toxic Megacolon | 0 Participants |
| Historical Control Antibiotics | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Colonic Perforations | 0 Participants |
| Historical Control Antibiotics | Number of Participants With Major Complications of rCDI From Baseline Through 24 Months | Emergency Colectomy | 1 Participants |
Secondary
Quality of Life (SF-36)
The Short Form - 36 quality of life questionnaire (SF-36) is a tool used to identify changes to quality of life following study treatment. It consists of a series of 36 questions relating to Mental and Physical health, summarized by a Physical Component Score (PCS) and Mental Component Score (MCS), respectively. Several sub-scales exist for each of the larger components; PCS includes PF, RP, BP, and GH while, MCS includes VT, SF, RE, and MH \[All abbreviations are defined in table\]. All Sub-Scale and Component Scores were calculated using Quality Metric Health Outcomes Scoring Software v4.5. The range of all scores is normalized from 0 (worst) to 100 (best). The data is presented for mean scores at baseline and 8-weeks post-treatment.
Time frame: Baseline
Population: Safety Population - The SP includes all participants who were enrolled and received at least dose of RBX2660.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RBX2660 Open-label | Quality of Life (SF-36) | Physical Component Summary (PCS) | 40.3 score on a scale | Standard Deviation 9.3 |
| RBX2660 Open-label | Quality of Life (SF-36) | Physical Functioning (PF) | 39.8 score on a scale | Standard Deviation 11.8 |
| RBX2660 Open-label | Quality of Life (SF-36) | Role Limitations Due to Physical Health (RP) | 38.0 score on a scale | Standard Deviation 11.3 |
| RBX2660 Open-label | Quality of Life (SF-36) | Bodily Pain (BP) | 44.5 score on a scale | Standard Deviation 11.5 |
| RBX2660 Open-label | Quality of Life (SF-36) | General Health Perceptions (GH) | 44.6 score on a scale | Standard Deviation 10.7 |
| RBX2660 Open-label | Quality of Life (SF-36) | Mental Component Summary (MCS) | 45.5 score on a scale | Standard Deviation 12.3 |
| RBX2660 Open-label | Quality of Life (SF-36) | Vitality (VT) | 41.9 score on a scale | Standard Deviation 11.5 |
| RBX2660 Open-label | Quality of Life (SF-36) | Social Functioning (SF) | 40.1 score on a scale | Standard Deviation 12.2 |
| RBX2660 Open-label | Quality of Life (SF-36) | Role Limitations Due to Emotional Problems (RE) | 43.6 score on a scale | Standard Deviation 12.2 |
| RBX2660 Open-label | Quality of Life (SF-36) | Mental Health (MH) | 46.3 score on a scale | Standard Deviation 11.7 |
Secondary
Quality of Life (SF-36)
The Short Form - 36 quality of life questionnaire (SF-36) is a tool used to identify changes to quality of life following study treatment. It consists of a series of 36 questions relating to Mental and Physical health, summarized by a Physical Component Score (PCS) and Mental Component Score (MCS), respectively. Several sub-scales exist for each of the larger components; PCS includes PF, RP, BP, and GH while, MCS includes VT, SF, RE, and MH \[All abbreviations are defined in table\]. All Sub-Scale and Component Scores were calculated using Quality Metric Health Outcomes Scoring Software v4.5. The range of all scores is normalized from 0 (worst) to 100 (best). The data is presented for mean scores at baseline and 8-weeks post-treatment.
Time frame: 8-Weeks
Population: Safety Population - The SP includes all participants who were enrolled and received at least dose of RBX2660.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RBX2660 Open-label | Quality of Life (SF-36) | Physical Component Summary (PCS) | 44.3 score on a scale | Standard Deviation 11.1 |
| RBX2660 Open-label | Quality of Life (SF-36) | Physical Functioning (PF) | 42.2 score on a scale | Standard Deviation 12.6 |
| RBX2660 Open-label | Quality of Life (SF-36) | Role Limitations Due to Physical Health (RP) | 43.8 score on a scale | Standard Deviation 10.7 |
| RBX2660 Open-label | Quality of Life (SF-36) | Bodily Pain (BP) | 48.6 score on a scale | Standard Deviation 11.8 |
| RBX2660 Open-label | Quality of Life (SF-36) | General Health Perceptions (GH) | 48.0 score on a scale | Standard Deviation 10 |
| RBX2660 Open-label | Quality of Life (SF-36) | Mental Component Summary (MCS) | 50.9 score on a scale | Standard Deviation 10.4 |
| RBX2660 Open-label | Quality of Life (SF-36) | Vitality (VT) | 49.0 score on a scale | Standard Deviation 10.5 |
| RBX2660 Open-label | Quality of Life (SF-36) | Social Functioning (SF) | 47.2 score on a scale | Standard Deviation 11.3 |
| RBX2660 Open-label | Quality of Life (SF-36) | Role Limitations Due to Emotional Problems (RE) | 46.9 score on a scale | Standard Deviation 11.8 |
| RBX2660 Open-label | Quality of Life (SF-36) | Mental Health (MH) | 51.0 score on a scale | Standard Deviation 10.6 |