Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| FMTADP | Other Identifier | UNC-CH |
Not provided
Not provided
Not provided
Due low efficacy of FMT in interim analysis.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| OpenBiome | INDUSTRY |
| Crohn's and Colitis Foundation | OTHER |
| The Broad Foundation | OTHER |
Not provided
Not provided
Not provided
Not provided
Antibiotic dependent pouchitis (ADP) is predestined to benefit from FMT, since bacterial dysbiosis, which can only be controlled with antibiotics, appears to be the major driver of the clinical symptoms. This is a proof of concept randomized placebo controlled trial, in which 50% of the patients will receive FMT and 50% will receive a placebo FMT. Additionally the trial offers an open label extension period.
FMT for ADP is a promising approach, given the documented role of bacteria in the pathogenesis. In contrast to patients with C. difficile colitis, in whom a single FMT is highly effective, in patients with Inflammatory Bowel Disease (IBD) an intensified therapy with daily or repeated FMT may be more beneficial. Whereas repeated endoscopic application are not feasible and repeated enema applications are not favored by patients a combination of endoscopic FMT and consecutive maintenance therapy with oral FMT using the FMT capsule G3 produced by OpenBiome to help establish the donor microbiome in the host seems to be the most promising approach. The objective of this trial is to evaluate the safety of FMT in patients with ADP and to estimate the effect size to be achieved from FMT therapy in patients with ADP for subsequent evaluation in a large definitive trial. A secondary objective is to study the microbial engraftment of donor FMT in the recipients.
This proof of concept randomized placebo controlled trial with an open label extension period will evaluate the safety and efficacy of an initial endoscopic FMT followed by 14 days of oral FMT. The study has two distinct outcomes, a clinical and translational aim, to investigate the effect of FMT in patients with ADP.
Aim1: Evaluation of safety, tolerability and clinical effectiveness (measured as clinical response or remission and discontinuation of antibiotic therapy) of FMT in patients with ADP.
Aim 2: Evaluation of the impact of FMT on the fecal bacterial microbiome in patients with ADP, which will provide functional data about possible mechanisms of this therapy.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active FMT, then open label FMT | Active Comparator | Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|
| Placebo FMT, then open label FMT | Placebo Comparator | Endoscopic application of Placebo FMT Lower Delivery followed by 2 weeks of treatment with Placebo FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active FMT, then open label FMT | Biological | Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With FMT Related Adverse Event | Number of patients with FMT related adverse event (classified according to MedDRA; lowest level term) and categorized according to CTCAE Version 4.0. The safety was assessed in the randomized placebo controlled segment of the study over 24 weeks after initial endoscopic FMT weeks and if the patient should enter the open label extension part of the study also for 24 weeks after initial open label FMT. 6 patients participated in the randomized arm and 5 patients in the open label extension arm. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients in Clinical Remission Week 4 After Endoscopic and Oral FMT | Clinical remission as defined by a composite assessment, of which all criteria need to be met: Clinical modified pouch diseases activity index (mPDAI) score ≤4 points and no need for antibiotic therapy at week 4. | 4 weeks |
| Number of Patients in Clinical Remission Week 16 |
Not provided
Inclusion Criteria:
or
- Need for ongoing antibiotic therapy (> 4 weeks) to maintain clinical remission and a history of at least 2 attempts in the last 24 months to stop antibiotic therapy resulting in pouchitis episodes.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Hans Herfarth, MD, PhD | University of North Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina | Chapel Hill | North Carolina | 27599 | United States |
The final results of the trial will be posted on clinical trials.gov. No individual patient data will be posted.
Not provided
Not provided
Not provided
Not provided
1 patient after screening since he met an exclusion criterion. 6 patients went on to randomization
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Active FMT, Then Open Label FMT | Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Blinded FMT Treatment (up to 24 Weeks) |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 30, 2017 |
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Placebo FMT, then open label FMT | Biological | Endoscopic application of Placebo FMT Lower Delivery followed by 2 weeks of treatment with Placebo FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|
|
Clinical remission as defined by a composite assessment, of which all criteria need to be met: Clinical mPDAI score ≤4 points and no need for antibiotic therapy at week 16. |
| 16 weeks |
| Number of Patients With Endoscopic Improvement Week 4 After Endoscopic and Oral FMT | Endoscopic improvement of active pouchitis (decrease from baseline in modified pouch disease activity index endoscopic subscore > 2 points) at week 4. | 4 weeks |
| Number of Patients With Clinical Response at Week 4 in Patients Entering the Trial With Active Pouchitis Symptoms | This outcome measure is for patients with active pouchitis symptoms entering the trial. Since all patients entered with inactive pouchitis no patient could be evaluated for this outcome. Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 4. | 4 weeks |
| Number of Patients With Clinical Response Week 8 and Active Pouchitis at Baseline | Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 8 of the randomized phase. | 8 weeks |
| Number of Patients With Clinical Response i at Week 16 and Active Pouchitis at Baseline | This outcome measure is for patients with active pouchitis symptoms entering the trial. Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 16. | 16 weeks |
| FG001 | Placebo FMT, Then Open Label FMT | Endoscopic application of Placebo FMT Lower Delivery followed by 2 weeks of treatment with Placebo FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
| FG002 | Open Label FMT Period | Participants who do not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study were offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an open label endoscopic FMT followed by 2 weeks of open label oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Open Label FMT Period (up to 24 Weeks) |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Active FMT, Then Open Label FMT | Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
| BG001 | Placebo FMT, Then Open Label FMT | Endoscopic application of Placebo FMT Lower Delivery followed by 2 weeks of treatment with Placebo FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With FMT Related Adverse Event | Number of patients with FMT related adverse event (classified according to MedDRA; lowest level term) and categorized according to CTCAE Version 4.0. The safety was assessed in the randomized placebo controlled segment of the study over 24 weeks after initial endoscopic FMT weeks and if the patient should enter the open label extension part of the study also for 24 weeks after initial open label FMT. 6 patients participated in the randomized arm and 5 patients in the open label extension arm. | Posted | Count of Participants | Participants | 24 weeks |
|
|
| |||||||||||||||||||||||||||||||||
| Secondary | Number of Patients in Clinical Remission Week 4 After Endoscopic and Oral FMT | Clinical remission as defined by a composite assessment, of which all criteria need to be met: Clinical modified pouch diseases activity index (mPDAI) score ≤4 points and no need for antibiotic therapy at week 4. | Posted | Count of Participants | Participants | 4 weeks |
| |||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients in Clinical Remission Week 16 | Clinical remission as defined by a composite assessment, of which all criteria need to be met: Clinical mPDAI score ≤4 points and no need for antibiotic therapy at week 16. | Posted | Count of Participants | Participants | 16 weeks |
| |||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients With Endoscopic Improvement Week 4 After Endoscopic and Oral FMT | Endoscopic improvement of active pouchitis (decrease from baseline in modified pouch disease activity index endoscopic subscore > 2 points) at week 4. | None of the patients in the randomized phase underwent an endoscopy at week 4 since they all relapsed before week 4. In the open label extension only 1 patient underwent endoscopy at week 4 and the pouch was endoscopically unchanged. | Posted | Count of Participants | Participants | 4 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients With Clinical Response at Week 4 in Patients Entering the Trial With Active Pouchitis Symptoms | This outcome measure is for patients with active pouchitis symptoms entering the trial. Since all patients entered with inactive pouchitis no patient could be evaluated for this outcome. Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 4. | Since all patients entered with inactive pouchitis no patient could be evaluated for this outcome. | Posted | 4 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients With Clinical Response Week 8 and Active Pouchitis at Baseline | Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 8 of the randomized phase. | Only 1 patient in the open label FMT completed the week 8 visit, but entered the trial in remission and thus did n to meet the criterion of a decrease of the clinical PDA sub core decrease | Posted | Count of Participants | Participants | 8 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients With Clinical Response i at Week 16 and Active Pouchitis at Baseline | This outcome measure is for patients with active pouchitis symptoms entering the trial. Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 16. | None of the patients in the trial entered the study with symptoms of active pouchitis | Posted | 16 weeks |
|
Adverse event were collected for 24 weeks after endoscopic FMT in the randomized phase. If patient the patient participated in the open label extension study period adverse events were collected for 24 weeks after endoscopic FMT in the open label extension phase.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Randomized Phase: Active FMT | Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG001 | Randomized Phase: Placebo | Endoscopic application of Placebo FMT Lower Delivery followed by 2 weeks of treatment with Placebo FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG002 | Open Label FMT | Participants who do not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study were offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an open label endoscopic FMT followed by 2 weeks of open label oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. | 0 | 5 | 0 | 5 | 5 | 5 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MEDRA 10.0 | Systematic Assessment |
| |
| Bloating | Gastrointestinal disorders | MEDRA 10.0 | Systematic Assessment |
| |
| Urgency | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MEDRA 10.0 | Systematic Assessment |
|
Due to the small sample size only exploratory analyses were performed.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hans Herfarth, MD | University of North Carolina at Chapel Hill | 919-966-6806 | hherf@med.unc.edu |
| Feb 12, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D019449 | Pouchitis |
| ID | Term |
|---|---|
| D007079 | Ileitis |
| D004751 | Enteritis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| D007077 | Ileal Diseases |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG002 | Open Label FMT | Participants who do not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study were offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an open label endoscopic FMT followed by 2 weeks of open label oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|
|
| OG002 | Open Label FMT | Participants who do not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study were offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an open label endoscopic FMT followed by 2 weeks of open label oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|
|
| OG002 | Open Label FMT | Participants who do not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study were offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an open label endoscopic FMT followed by 2 weeks of open label oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|
|
| OG002 | Open Label FMT | Participants who do not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study were offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an open label endoscopic FMT followed by 2 weeks of open label oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|
| OG002 | Open Label FMT | Participants who do not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study were offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an open label endoscopic FMT followed by 2 weeks of open label oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|
|
| OG002 | Open Label FMT | Participants who do not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study were offered the possibility to participate in open label extension after at least 10 day of antibiotic therapy with an open label endoscopic FMT followed by 2 weeks of open label oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT. |
|