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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for individuals with both inflammatory bowel disease (IBD) and recurrent Clostridium difficile infection (CDI). It compares two treatments: fecal microbiota transplantation (FMT), which uses healthy donor stool to restore gut bacteria balance, combined with either Bezlotoxumab (Bezlo), a drug that helps prevent CDI recurrence, or a placebo. Participants must have experienced at least two episodes of CDI, have confirmed IBD, and be receiving FMT as standard care. The goal is to evaluate the effectiveness of these treatments in managing both conditions. As a Phase 2 trial, the research focuses on assessing the treatment's efficacy in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fecal microbiota transplantation (FMT) is generally safe for people with inflammatory bowel disease (IBD) who also experience recurring Clostridioides difficile infections (CDI). Studies have found that FMT is well-tolerated and effective for these patients. Bezlotoxumab helps prevent CDI recurrence by neutralizing the toxins produced by the bacteria.

Although combining FMT with bezlotoxumab hasn't demonstrated a clear additional benefit over FMT alone, no major safety issues have been reported with their combined use. Overall, both FMT and bezlotoxumab have been used without major problems in patients similar to those in this trial, suggesting that the treatments are likely safe for study participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Fecal Microbiota Transplantation (FMT) combined with bezlotoxumab for treating IBD and C. difficile infection because this approach offers a novel way to restore gut health. Unlike traditional antibiotics or therapies that target the bacteria directly, FMT aims to rebalance the gut microbiome by introducing beneficial bacteria from healthy donors. Bezlotoxumab, an antibody, prevents recurrence by neutralizing the toxin produced by C. difficile. This combination not only targets the infection but also helps prevent it from coming back, making it a promising alternative to conventional treatments.

What evidence suggests that this trial's treatments could be effective for IBD and C. difficile infection?

Research has shown that fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (rCDI). Studies have found that FMT can restore a healthy balance of gut bacteria, crucial for combating infections like CDI. In this trial, one group of participants will receive FMT combined with Bezlotoxumab, which has successfully reduced the recurrence of CDI. Another group will receive FMT with a placebo. Combining these treatments might enhance their effectiveness, particularly for patients with inflammatory bowel disease (IBD) who also have CDI. Although data on this specific combination is limited, existing research suggests it could be promising for addressing both conditions. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38501667/

Outcomes After Fecal Microbiota Transplantation in ... We assess the impact of FMT in combination with bezlotoxumab in patients with inflammatory bowel disease and rCDI.

2. journals.lww.com journals.lww.com/ajg/fulltext/2024/10001/s1045_fecal_microbiota_transplantation__fmt__with.1046.aspx

S1045 Fecal Microbiota Transplantation (FMT ... This is the first clinical trial to assess the effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1931312823001245

Beneficial effects of fecal microbiota transplantation in ... Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI).

4. gastrojournal.org gastrojournal.org/article/S0016-5085(24)00041-6/fulltext

AGA Clinical Practice Guideline on Fecal Microbiota ... Outcomes of fecal microbiota transplantation for Clostridium difficile infection in patients with inflammatory bowel disease. Dig Dis Sci. 2017; 62:2870-2875.

5. academic.oup.com academic.oup.com/ofid/article/10/2/ofad028/7005371

Real-world Use of Bezlotoxumab and Fecal Microbiota ... Both treatments had similar effectiveness in preventing CDI recurrence despite their application to different populations. bezlotoxumab, Clostridioides ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9907541/

Real-world Use of Bezlotoxumab and Fecal Microbiota ... We aimed to describe the frequency of use and effectiveness of bezlotoxumab (BZX) and fecal microbiota transplantation (FMT) in patients with Clostridioides ...

7. medscape.com medscape.com/viewarticle/does-bezlotoxumab-boost-fmt-efficacy-ibd-patients-recurrent-2024a1000ki6

FMT With Bezlotoxumab in IBD Patients With Recurrent CDI A randomized controlled trial finds no clear benefit of adding bezlotoxumab to FMT in patients with IBD and recurrent C difficile infection.

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/75/NCT03829475/Prot_SAP_000.pdf

Version 7: 01/10/22 Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B, indicated to reduce recurrence of Clostridium difficile infection (CDI) ...