FMT + Bezlotoxumab for IBD and C. Difficile Infection

(ICON-2 Trial)

Overseen By Emma McClure

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Non-anti-CDI antibiotics

Disqualifiers: Pregnancy, Heart failure, Surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 day

61 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized controlled trial to assess the clinical and microbiological impacts of FMT in combination with Bezlotoxumab (bezlo) compared to FMT in combination with placebo in patients with both inflammatory bowel disease (IBD) a and clostridium difficile infection (CDI). The investigators will prospectively enroll up to 150 IBD-CDI patients from 4 tertiary care FMT referral centers. Patients will be randomized 1:1 to either receive FMT in combination with Bezlo of FMT and a placebo infusion. Donor stool from healthy donors will be obtained from OpenBiome. OpenBiome is a nonprofit 501(c)(3) organization that provides hospitals with screened, filtered, and frozen material ready for clinical use. Patients will be enrolled and followed prospectively for 3 months post therapy. Stool and blood samples as well as clinical data will be collected at baseline, week 1, 8 and 12.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you need continued non-anti-CDI antibiotic therapy, so you might need to adjust some medications. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment FMT + Bezlotoxumab for IBD and C. Difficile Infection?

Research shows that fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridioides difficile infection, with cure rates up to 90%. There is also growing evidence that FMT can be beneficial for patients with inflammatory bowel disease (IBD), although some studies suggest a risk of worsening IBD symptoms after FMT. ^{1 2 3 4 5}

Is FMT safe for treating IBD and C. difficile infection?

Fecal microbiota transplantation (FMT) is generally considered safe for treating recurrent C. difficile infections, with cure rates up to 90%. While there is growing evidence supporting its safety in patients with inflammatory bowel disease (IBD), more research is needed to fully understand its long-term safety and effects. ^{1 2 4 6 7}

How is the treatment FMT + Bezlotoxumab unique for IBD and C. Difficile Infection?

FMT (Fecal Microbiota Transplantation) is unique because it involves transferring stool from a healthy donor to a patient to restore a healthy balance of bacteria in the gut, which is different from traditional drug treatments. This approach is particularly novel for treating both Clostridioides difficile infection and inflammatory bowel disease (IBD), as it targets the gut microbiome directly, unlike standard medications that may not address the underlying microbial imbalance. ^{1 4 8 9 10}

Eligibility Criteria

This trial is for adults over 18 with inflammatory bowel disease (IBD) and recurrent Clostridium difficile infection (CDI), who are undergoing fecal microbiota transplantation (FMT) as standard care. Participants must have had at least two CDI episodes, but not received FMT in the past year or be pregnant/breastfeeding. Those with severe allergies, life expectancy under six months, or certain medical conditions are excluded.

Inclusion Criteria

I am receiving a fecal transplant through a colonoscopy for C. diff infection.

I have had Clostridium difficile infection (CDI) at least twice.

I have been diagnosed with IBD (ulcerative colitis, Crohn's disease, or indeterminate colitis).

Exclusion Criteria

I am not infected with EBV or CMV and take 3 or more drugs for immune suppression.

My doctor thinks some conditions or medications I have might make the treatment risky for me.

Doctors think you might not live for more than 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FMT via colonoscopy and either Bezlotoxumab or placebo infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

4 visits (in-person) at baseline, week 1, 8, and 12

Treatment Details

Interventions

• Bezlotoxumab
• Fecal Microbiota Transplantation
• Placebo

Trial Overview The ICON-2 trial tests if adding Bezlotoxumab to FMT is more effective than FMT with a placebo in treating IBD patients with CDI. Up to 150 participants will be randomly assigned to either treatment group and monitored for three months using stool and blood samples along with clinical data.

Participant Groups

Group I: FMT + Bezlo Experimental Treatment 2 Interventions

Patients in this arm will received an FMT via colonoscopy ( 250ml) as well as a single IV infusion of bezlotoxumab (10mg/kg) that will take place over 60 mins.

Group II: FMT + Placebo Placebo Group 2 Interventions

Patients in this arm will receive a single FMT via colonoscopy (250ml) and a placebo (saline) infusion (250cc) over

Fecal Microbiota Transplantation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Approved in European Union as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)
• Other gastrointestinal disorders

Approved in Canada as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

Fecal microbiota transplantation (FMT) is a safe and effective treatment for Clostridioides difficile infection (CDI) in patients who also have inflammatory bowel disease (IBD).

There is ongoing research into the potential of FMT as a treatment for IBD itself, given the link between gut microbiome alterations and conditions like ulcerative colitis and Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FMT: What's Next? A Narrative Review of Fecal Microbiota Transplantation in Clostridioides difficile Infection and Inflammatory Bowel Disease. Patwa, SA., Ward, C., Kelly, CR.[2022]

In a survey of 262 ulcerative colitis patients, 56.1% expressed willingness to undergo fecal microbiota transplantation (FMT) as a treatment option, motivated primarily by the effectiveness of the procedure and the failure of other therapies.

Concerns about FMT included the potential transmission of infectious agents and contamination of the stool graft, highlighting the need for safe implementation practices in this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. Roggenbrod, S., Schuler, C., Haller, B., et al.[2022]

In a review of 12 published studies on fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD), only one study suggested a significant donor effect, while the majority showed no statistically significant differences in efficacy based on donor material.

Despite the lack of strong evidence for donor effects, the study highlights that the existing data cannot completely rule out their potential clinical importance, indicating a need for larger, well-designed trials to explore this further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease. Olesen, SW., Gerardin, Y.[2021]

Fecal microbiota transplantation (FMT) is emerging as a promising strategy to restore normal gut microbiota in patients with inflammatory bowel disease (IBD), potentially complementing existing immune modulation treatments.

While FMT shows potential efficacy, there are still uncertainties regarding the best predictors for treatment response, optimal administration methods, and the ideal characteristics of the transplanted microbiota, highlighting the need for further research on long-term outcomes and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of fecal microbiota transplantation in inflammatory bowel disease. D'Odorico, I., Di Bella, S., Monticelli, J., et al.[2018]

Fecal microbiota transplantation (FMT) has become a key treatment for Clostridium difficile infection, but its efficacy and safety in patients with underlying inflammatory bowel disease (IBD) are not well established, particularly regarding the risk of IBD flare-ups.

Emerging evidence suggests that FMT may also be beneficial for treating IBD itself, with promising results from randomized trials in ulcerative colitis, although the variability in study outcomes means more research is needed to clarify its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Landscape and Lessons from Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Past, Present, and Future. Allegretti, J., Eysenbach, LM., El-Nachef, N., et al.[2022]

A 71-year-old man with immune checkpoint inhibitor (ICI) colitis, which did not respond to standard treatments like corticosteroids and biologic therapy, showed improvement after receiving fecal microbiota transplantation (FMT).

This case suggests that FMT may be a promising alternative treatment for severe ICI colitis, especially in patients who do not respond to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis. Fasanello, MK., Robillard, KT., Boland, PM., et al.[2020]

In a study of 15 patients with steroid-dependent ulcerative colitis (UC), a step-up fecal microbiota transplantation (FMT) strategy led to clinical improvement in 57.1% of patients, allowing them to discontinue steroid use.

The successful treatment was associated with significant changes in gut microbiota composition, resembling that of the donor, and no severe adverse events were reported, indicating the safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. Cui, B., Li, P., Xu, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

FMT: What's Next? A Narrative Review of Fecal Microbiota Transplantation in Clostridioides difficile Infection and Inflammatory Bowel Disease. [2022]

2. Belgium pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in ulcerative colitis. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

The risk of inflammatory bowel disease flares after fecal microbiota transplantation: Systematic review and meta-analysis. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Role of fecal microbiota transplantation in inflammatory bowel disease. [2018]

7. England pubmed.ncbi.nlm.nih.gov

The Current Landscape and Lessons from Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Past, Present, and Future. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Endoscopic Delivery of Fecal Biotherapy in Inflammatory Bowel Disease. [2017]