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

NCT02782325 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 16-1310FMTADP
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pouchitis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Number of Patients in Clinical Remission Week 4 After Endoscopic and Oral FMT

  4 weeks

• Number of Patients in Clinical Remission Week 16

  16 weeks

• Number of Patients With Endoscopic Improvement Week 4 After Endoscopic and Oral FMT

  4 weeks

• Number of Patients With Clinical Response at Week 4 in Patients Entering the Trial With Active Pouchitis Symptoms

  4 weeks

• Number of Patients With Clinical Response Week 8 and Active Pouchitis at Baseline

  8 weeks

Study Arms (2)

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.

Biological: Active FMT, then 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.

Biological: Placebo FMT, then open label FMT

Interventions

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.

Also known as: Active FMT

Active FMT, then open label FMT

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.

Also known as: Placebo FMT

Placebo FMT, then open label FMT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Man or woman between 18 and 70 years of age.
• Ileal Pouch-Anal Anastomosis (IPAA) after colectomy for ulcerative colitis
• Active pouchitis, defined as a modified pouch disease activity index (mPDAI) ≥ 5 and a history of ≥ 4 antibiotic therapies for pouchitis in the last 12 months
• \- 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.

You may not qualify if:

• Treatment with biologics (e.g. infliximab, adalimumab, golimumab, vedolizumab)
• Treatment with immunomodulators (azathioprine, 6-mercaptopurine (6-MP), methotrexate), steroids or any investigational drugs
• Use of cholestyramine
• Crohn's disease of the pouch
• Known cytomegalovirus infection of the pouch
• Clostridium difficile infection
• Isolated cuffitis
• Clinical significant strictures of the pouch inlet or outlet
• Concurrent intestinal obstruction
• History of familial adenomatous polyposis
• History of uncontrolled lactose intolerance
• History of confirmed (serological test and/or histology) celiac disease
• Pregnancy, breast feeding, or planning to become pregnant during the trial
• Non - steroidal inflammatory medications (NSAIDs) as long-term treatment, defined as use for at least 4 days a week each month
• Dysphagia (oropharyngeal, esophageal, functional, neuromuscular)

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• OpenBiome: collaborator
• Crohn's and Colitis Foundation: collaborator
• The Broad Foundation: collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Pouchitis

Condition Hierarchy (Ancestors)

Ileitis; Enteritis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Ileal Diseases

Limitations and Caveats

Due to the small sample size only exploratory analyses were performed.

Results Point of Contact

• Title: Hans Herfarth, MD
• Organization: University of North Carolina at Chapel Hill

hherf@med.unc.edu

919-966-6806

Study Officials

• Hans Herfarth, MD, PhD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2016
• First Posted: May 25, 2016
• Study Start: June 1, 2017
• Primary Completion: December 3, 2018
• Study Completion: December 3, 2018
• Last Updated: May 14, 2019
• Results First Posted: May 14, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)