Recurrent Clostridium Difficile Infection
Conditions
Keywords
Clostridium difficile, C diff, Microbiota Restoration Therapy, MRT, microbiota suspension, CDI, CDAD, Fecal transplant, Fecal Microbiota Transplant, FMT, Diarrhea, Fecal bacteriotherapy
Brief summary
This study will assess the safety of a new biologic drug, RBX2660 (microbiota suspension) as a treatment for recurrent Clostridium difficile-associated diarrhea (CDAD), which is the primary symptom of recurrent Clostridium difficile infection. All eligible subjects will receive RBX2660.
Detailed description
This is the first study of a microbiota suspension derived from intestinal microbes. The primary assessments for this open label, multi-center study are (i) occurrence of product-related adverse events and (ii) resolution of CDAD at 56 days after administration of RBX2660. Subjects will also be assessed for time to CDAD recurrence, quality of life changes, and number of hospitalizations and length of stay for recurrent CDAD. Study visits will be at 7, 30, and 60 days after RBX2660 administration with additional follow-up at 3 and 6 months post treatment. Patients who have had at least two recurrences of CDAD after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDAD resulting in hospitalization may be eligible for the study.
Interventions
BIOLOGICALRBX2660 (microbiota suspension)
Sponsors
Rebiotix Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years * Medical record documentation of CDAD either: a) at least two recurrences after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or b) have had at least two episodes of severe CDAD resulting in hospitalization. * Willing and able to have an enema(s). * Already taking or will start a course of oral antibiotics for CDAD symptoms for 10-14 days, including at least seven days of oral vancomycin. * Willing and able to complete the required subject diary.
Exclusion criteria
* Continued (uncontrolled) CDAD after completing a 10-14 day course of oral antibiotics. * Requires antibiotic therapy for a condition other than CDAD. * Previous fecal transplant prior to study enrollment. * History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis. * History of irritable bowel syndrome (IBS). * History of chronic diarrhea. * History of celiac disease. * History of cirrhosis of the liver or ascites. * Disease symptoms caused by a confirmed intestinal pathogen other than Clostridium difficile. * Has a colostomy. * Intraabdominal surgery within the last 60 days. * Evidence of active, severe colitis. * History of short gut syndrome or motility disorders. * Requires the regular use of medications that affect bowel motility (e.g., metoclopramide, narcotics, loperamide). * Planned therapy in the next 3 months that may cause diarrhea (e.g., chemotherapy). * Planned surgery requiring perioperative antibiotics within 6 months of study enrollment. * Life expectancy of \< 12 months. * Compromised immune system, e.g., HIV infection (any CD4 count); AIDS-defining diagnosis or CD4 \<200/mm3; inherited/primary immune disorders; immunodeficient or immunosuppressed due to a medical condition or medication; current or recent (\< 90 days) treatment with chemotherapy; or current or recent (\< 90 days) treatment with immunosuppressant medications. * Taking steroids (≥ 20 mg a day) or is expected to be on steroids for more than 30 days after enrollment. * Neutropenia (white blood cell count \<1000 cells/µL).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Serious Adverse Events Through 56 Days After the Last Treatment With RBX2660 | 56 days | Safety will be assessed by evaluating the incidence of serious adverse events through 56 days after the last treatment with RBX2660. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-treatment Hospitalization Data | 6 months | number of ICU days was collected for subjects who received RBX2660 and who were subsequently hospitalized for recurrent CDAD treatment. |
| Long-term Safety | 6 months | The incidence of serious adverse events will be assessed through 6 months after the last treatment with RBX2660. |
| Absence of CDAD at 56 Days | 56 days | Number of participants who were determined to be free of CDAD at Day 56 after receiving their last dose of RBX2660. |
| Quality of Life (SF-36) | 60 days | Quality of Life (SF-36) will be assessed by comparing the subject's baseline quality of life score to his/her scores obtained at the 7-, 30- and 60-day follow-up visits. The scale is from 0-100, with higher scores meaning better outcomes. |
Countries
United States
Participant flow
Recruitment details
Recruitment was from 07/15/13 to 12/16/13 at 13 medical clinics in the United States. Recruiment was performed by trained investigators and study coordinators.
Participants by arm
| Arm | Count |
|---|---|
| RBX2660 (Microbiota Suspension) Open-label; all subjects received RBX2660 | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | RBX2660 (Microbiota Suspension) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 66.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 34 |
| serious Total, serious adverse events | 7 / 34 |
Outcome results
Primary
Incidence of Serious Adverse Events Through 56 Days After the Last Treatment With RBX2660
Safety will be assessed by evaluating the incidence of serious adverse events through 56 days after the last treatment with RBX2660.
Time frame: 56 days
Population: 31 subjects had evaluable data at 56 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RBX2660 (Microbiota Suspension) | Incidence of Serious Adverse Events Through 56 Days After the Last Treatment With RBX2660 | 10 number of reported SAEs through 56 days |
Secondary
Absence of CDAD at 56 Days
Number of participants who were determined to be free of CDAD at Day 56 after receiving their last dose of RBX2660.
Time frame: 56 days
Population: 31 subjects had evaluable data at 56 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RBX2660 (Microbiota Suspension) | Absence of CDAD at 56 Days | 27 participants with treatment success |
Secondary
Long-term Safety
The incidence of serious adverse events will be assessed through 6 months after the last treatment with RBX2660.
Time frame: 6 months
Population: 31 subjects had evaluable data at 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RBX2660 (Microbiota Suspension) | Long-term Safety | 20 number of reported SAEs |
Secondary
Post-treatment Hospitalization Data
number of ICU days was collected for subjects who received RBX2660 and who were subsequently hospitalized for recurrent CDAD treatment.
Time frame: 6 months
Population: 31 subjects had evaluable data at 6 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RBX2660 (Microbiota Suspension) | Post-treatment Hospitalization Data | 0 number of particpants' ICU days |
Secondary
Quality of Life (SF-36)
Quality of Life (SF-36) will be assessed by comparing the subject's baseline quality of life score to his/her scores obtained at the 7-, 30- and 60-day follow-up visits. The scale is from 0-100, with higher scores meaning better outcomes.
Time frame: 60 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RBX2660 (Microbiota Suspension) | Quality of Life (SF-36) | Baseline | 42.2 score on a scale | Standard Deviation 14.6 |
| RBX2660 (Microbiota Suspension) | Quality of Life (SF-36) | 7-Day | 47.7 score on a scale | Standard Deviation 11.7 |
| RBX2660 (Microbiota Suspension) | Quality of Life (SF-36) | 30-DAy | 48.6 score on a scale | Standard Deviation 11.8 |
| RBX2660 (Microbiota Suspension) | Quality of Life (SF-36) | 60-Day | 51.3 score on a scale | Standard Deviation 11.2 |