Fecal Microbiota Transplantation for Chronic Granulomatous Disease-Associated Colitis

Study Description:

This is a prospective, single-site, single-arm, open-label pilot trial to evaluate the use of fecal microbiota transplantation (FMT) delivered by colonoscopy as a treatment for chronic granulomatous disease (CGD)-associated colitis (AC). Participants will be evaluated for changes in intestinal inflammation, the microbiome, and symptoms associated with CGD-AC. It is hypothesized that FMT will reduce intestinal inflammation as measured by fecal calprotectin within 1 month compared to baseline (pre-FMT); there will be associated changes in the underlying stool microbiome and improvement in clinical symptoms.

Primary Objective:

To evaluate the change in intestinal inflammation pre-FMT vs post-FMT.

Secondary Objectives:

• To evaluate the change in the stool microbiome pre-FMT vs post-FMT.
• To evaluate changes in clinical symptoms pre-FMT and post-FMT.
• Preliminary evaluation of the safety of FMT in CGD-AC.

Tertiary/Exploratory Objectives:

• To evaluate other markers of intestinal and systemic inflammation pre-FMT and post-FMT.
• To evaluate a washout period for beneficial effects of FMT on fecal calprotectin and the microbiome.
• To evaluate the effect of FMT on antibiotic resistance in CGD-AC.

Primary Endpoint:

Difference in fecal calprotectin pre-FMT within 1 month post-FMT.

Secondary Endpoints:

• Differences in alpha diversity, beta diversity, and relative abundance of taxa pre-FMT and within 1 month post-FMT. Assessment of engraftment of donor microbiome.
• Difference in Patient Reported Outcome-2 (PRO-2) pre-FMT and within 1 month post-FMT.
• Treatment-emergent adverse events (TEAEs).

Tertiary/Exploratory Endpoints:

• Changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) pre-FMT and post-FMT; changes in Simple Endoscopic Score for Crohn s Disease (SES-CD) pre-FMT and post-FMT in those who undergo a second colonoscopy; changes in magnetic resonance (MR) enterography findings in those who undergo a second MR enterography.
• Changes in fecal calprotectin and microbiome indices over 6 months post-FMT.
• Changes in antibiotic resistance genes in stool microbiome pre-FMT and post-FMT.

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Aged >=10 to <=60 years.
• Able to provide informed consent (for ages >=18 years) or has a parent or guardian who can provide informed consent on their behalf (for ages <18 years).
• Have confirmed prior diagnoses of CGD and CGD-AC (or CGD-IBD with evidence of colitis on colonoscopy).
• Fecal calprotectin level >=200 microgram/g.
• HBI score >=5 (to be evaluated on Day 1).
• No planned change in systemic antibiotic regimen for CGD for 1 month preceding FMT.
• No planned escalation in CGD-IBD treatment for 1 month preceding FMT.
• If taking monoclonal antibodies for CGD-IBD, the dose must be stable for 12 weeks with no planned escalation.
• Participants who can become pregnant must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy, starting at screening until the end of study participation. Highly effective methods include a barrier (eg, condom, diaphragm, cervical cap), intrauterine device, or hormonal contraception.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Evidence of acute GI infection, including active GI abscesses.
• Presence of C difficile toxin gene in stool, as identified by PCR, in screening period.
• History of intestinal obstruction definitively related to CGD-IBD.
• History of fistulizing CGD-IBD or CGD-IBD intra-abdominal abscesses.
• History of CGD-IBD related non-transversable intestinal strictures.
• History of AEs attributable to previous FMT.
• History of significant liver disease (eg, biopsy-proven nodular regenerative hyperplasia), including portal hypertension or cirrhosis.
• Pregnant or breastfeeding.
• History of severe food allergy.
• Any contraindication to having colonoscopy under anesthesia.
• Any condition that, in the opinion of the investigator, contraindicates participation in this study.