Trial Outcomes & Findings for Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP) (NCT NCT02782325)

Last Updated: 2019-05-14

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

6 participants

Primary outcome timeframe

24 weeks

Results posted on

2019-05-14

Participant Flow

1 patient after screening since he met an exclusion criterion. 6 patients went on to randomization

Participant milestones

Participant milestones
Measure	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.	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.	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.
Blinded FMT Treatment (up to 24 Weeks) STARTED	4	2	0
Blinded FMT Treatment (up to 24 Weeks) COMPLETED	0	0	0
Blinded FMT Treatment (up to 24 Weeks) NOT COMPLETED	4	2	0
Open Label FMT Period (up to 24 Weeks) STARTED	0	0	5
Open Label FMT Period (up to 24 Weeks) COMPLETED	0	0	1
Open Label FMT Period (up to 24 Weeks) NOT COMPLETED	0	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Blinded FMT Treatment (up to 24 Weeks) Lack of Efficacy	4	2	0
Open Label FMT Period (up to 24 Weeks) Lack of Efficacy	0	0	4

Baseline Characteristics

Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active FMT, Then Open Label FMT n=4 Participants 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 n=2 Participants 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.	Total n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Outcome measures

Outcome measures
Measure	Randomized Phase: Active FMT n=4 Participants 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.	Randomized Phase: Placebo n=2 Participants 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.	Open Label FMT n=5 Participants 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.
Number of Patients With FMT Related Adverse Event	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 4 weeks

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.

Outcome measures

Outcome measures
Measure	Randomized Phase: Active FMT n=4 Participants 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.	Randomized Phase: Placebo n=2 Participants 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.	Open Label FMT n=5 Participants 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.
Number of Patients in Clinical Remission Week 4 After Endoscopic and Oral FMT	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 16 weeks

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.

Outcome measures

Outcome measures
Measure	Randomized Phase: Active FMT n=4 Participants 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.	Randomized Phase: Placebo n=2 Participants 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.	Open Label FMT n=5 Participants 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.
Number of Patients in Clinical Remission Week 16	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: 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.

Endoscopic improvement of active pouchitis (decrease from baseline in modified pouch disease activity index endoscopic subscore \> 2 points) at week 4.

Outcome measures

Outcome measures
Measure	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.	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.	Open Label FMT n=1 Participants 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.
Number of Patients With Endoscopic Improvement Week 4 After Endoscopic and Oral FMT	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: Since all patients entered with inactive pouchitis no patient could be evaluated for this outcome.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 weeks

Population: 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

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.

Outcome measures

Outcome measures
Measure	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.	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.	Open Label FMT n=1 Participants 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.
Number of Patients With Clinical Response Week 8 and Active Pouchitis at Baseline	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 16 weeks

Population: None of the patients in the trial entered the study with symptoms of active pouchitis

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.

Outcome measures

Outcome data not reported

Adverse Events

Randomized Phase: Active FMT

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Randomized Phase: Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Open Label FMT

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Randomized Phase: Active FMT n=4 participants at risk 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.	Randomized Phase: Placebo n=2 participants at risk 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.	Open Label FMT n=5 participants at risk 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.
Gastrointestinal disorders Nausea	0.00% 0/4 • 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.	50.0% 1/2 • Number of events 1 • 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.	0.00% 0/5 • 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.
Gastrointestinal disorders Bloating	75.0% 3/4 • Number of events 3 • 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.	100.0% 2/2 • Number of events 2 • 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.	60.0% 3/5 • Number of events 3 • 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.
Gastrointestinal disorders Urgency	75.0% 3/4 • Number of events 3 • 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.	0.00% 0/2 • 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.	20.0% 1/5 • Number of events 1 • 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.
Gastrointestinal disorders Diarrhea	75.0% 3/4 • Number of events 3 • 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.	0.00% 0/2 • 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.	40.0% 2/5 • Number of events 2 • 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.
General disorders Fatigue	0.00% 0/4 • 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.	50.0% 1/2 • Number of events 1 • 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.	20.0% 1/5 • Number of events 1 • 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.

Additional Information

Hans Herfarth, MD

University of North Carolina at Chapel Hill

Phone: 919-966-6806

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place