Microbiome Treatment for Colitis

(FMT-ELIMINATE Trial)

Overseen By Amy Rose, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Diwakar Davar

Must be taking: Corticosteroids

Must not be taking: Biologics

Disqualifiers: Immunodeficiency, Immunosuppression, MDRO risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Multiple retrospective studies suggest that the administration of corticosteroids to treat irAEs is safe, and does not compromise efficacy of ICI therapy in cancer patients. While \~67% of patients respond to corticosteroids, 33% of patients require biologic therapy such as TNFα inhibitors (e.g. infliximab), integrin α4β7 inhibitors (e.g. vedolizumab), or JAK/STAT inhibitors (e.g. tofactinib). This study aims to determine that distinct pathobionts govern the development of irCAE and IMC; and that the administration of hdFMT may reverse steroid-refractory irCAEs or IMC. The use of hdFMT has been shown to be effective in steroid and biologic (TNFα and/or integrin α₄β₇ inhibitor) refractory colitis in PD-1 and/or CTLA-4 ICI treated cancer patients in single-institution case series.

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 must not have received certain biologic therapies before enrolling, and you should not be on other forms of immunosuppressive therapy besides steroids or biologics within 7 days prior to the trial.

What data supports the effectiveness of the treatment MTP-101-C for colitis?

Research shows that fecal microbiota transplantation (FMT), a treatment similar to MTP-101-C, has been effective in improving symptoms in patients with immune-mediated colitis and ulcerative colitis. In one study, 83% of patients with severe colitis symptoms improved after FMT, and 92% achieved clinical remission, suggesting that altering gut bacteria can help manage colitis. ^{1 2 3 4 5}

Is the microbiome treatment for colitis safe for humans?

Fecal microbiota transplant (FMT), a type of microbiome treatment, has been used safely in treating conditions like ulcerative colitis and Clostridium difficile infection, but more studies are needed to fully understand the risks and best practices for its use in inflammatory bowel diseases. ^{1 6 7 8 9}

How is the treatment MTP-101-C for colitis different from other treatments?

MTP-101-C is unique because it focuses on altering the gut microbiome (the community of bacteria in the intestines) to treat colitis, which is different from traditional treatments that often target inflammation directly. This approach is similar to fecal microbiota transplantation, which has shown promise in inducing remission in colitis by changing the bacterial composition in the gut. ^{10 11 12 13 14}

Research Team

Diwakar Davar, MD

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

This trial is for individuals with immune-related skin issues like eczema or colitis that haven't improved after steroid treatment. Participants should have these conditions due to cancer immunotherapy and must not respond well to other biologic treatments.

Inclusion Criteria

Participant provides written informed consent for the trial

Willingness to use contraception for the duration of trial participation

Willingness to undergo correlative blood and stool sampling

Exclusion Criteria

Patients at high risk of MDRO colonization

I have experienced multiple immune-related side effects.

I have not received any live vaccines in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive MTP-101-C (encapsulated fecal microbiota) for 28 days, with steroids tapered rapidly

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including endpoint assessments and biospecimen collection

2 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored for resolution of symptoms and adverse events up to 2 months

4 weeks

Treatment Details

Interventions

• MTP-101-C

Trial Overview The study tests MTP-101-C, a healthy-donor microbiome therapy, on patients who didn't get better from steroids or biologics for their skin problems or colitis caused by cancer treatments.

Participant Groups

Group I: MTP-101-C (Cohort 2: Steroid R/R biologic-naive colitis) Experimental Treatment 1 Intervention

Patients given MTP-101-C (encapsulated fecal microbiota, containing \~5 x 1011 bacteria derived from healthy donors). Dosing: 5 capsules/day (Day 1); 2 capsules/day (D2-D28)

Group II: MTP-101-C (Cohort 1: Steroid R/R biologic-naive dermatitis) Experimental Treatment 1 Intervention

Patients given MTP-101-C (encapsulated fecal microbiota, containing \~5 x 1011 bacteria derived from healthy donors). Dosing: 5 capsules/day (Day 1); 2 capsules/day (D2-D28)

Who Is Running the Clinical Trial?

Diwakar Davar

Lead Sponsor

Trials

12

Recruited

420+

Stanley Marks Fund for Cancer Research

Collaborator

Trials

1

Recruited

30+

Cures Within Reach

Collaborator

Trials

25

Recruited

2,100+

Findings from Research

In a study involving 20 patients with recurrent ulcerative colitis, a single fresh fecal microbiota transplant (FMT) led to a significant reduction in disease symptoms compared to a control group, with 90% of FMT patients meeting the primary endpoint at week 8.

The treatment was well-tolerated with no significant adverse events during long-term follow-up, suggesting that FMT could be a safe and effective long-term therapy for inducing remission in active ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study. Fang, H., Fu, L., Li, X., et al.[2021]

In a case series of 12 patients with severe immune-mediated colitis (IMC) caused by immune checkpoint inhibitors, 83% experienced symptom improvement after fecal microbiota transplantation (FMT), and 92% achieved clinical remission by the end of the study.

Analysis of stool samples indicated that successful FMT responses were linked to specific microbial changes, including increased diversity and the presence of beneficial bacteria like Collinsella and Bifidobacterium, suggesting that gut microbiota composition plays a crucial role in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor-induced colitis. Halsey, TM., Thomas, AS., Hayase, T., et al.[2023]

Fecal microbiota transplantation (FMT) was found to be a safe and effective treatment for allergic colitis in infants, with 17 out of 19 infants experiencing symptom relief within 2 days and no relapses over a 15-month follow-up period.

Post-FMT analysis showed significant changes in gut microbiota composition, including increased diversity and a shift in bacterial populations, indicating that FMT not only alleviates symptoms but also helps restore a healthier gut microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment. Liu, SX., Li, YH., Dai, WK., et al.[2019]

In a study of 65 IBD patients, those treated with anti-TNF antibodies showed significant changes in their gut microbiome, particularly a decrease in Proteobacteria and an increase in Bacteroidetes, which were linked to clinical remission.

The research also found that patients in remission had a 1.7-fold higher capacity for butyrate production, a beneficial short-chain fatty acid, suggesting that microbial butyrate synthesis could be a key indicator of treatment effectiveness in IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbial Butyrate Synthesis Indicates Therapeutic Efficacy of Azathioprine in IBD Patients. Effenberger, M., Reider, S., Waschina, S., et al.[2021]

Research indicates that the gut microbiome plays a crucial role in Crohn's disease and ulcerative colitis, with studies showing reduced microbial diversity and changes in specific bacterial populations associated with disease severity.

Longitudinal studies suggest that monitoring microbial changes can help predict disease activity and treatment response, highlighting the potential for microbiome-based biomarkers in improving patient risk stratification and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiome-Based Biomarkers for IBD. Ananthakrishnan, AN.[2021]

Combining mesalamine with probiotics significantly improves clinical efficacy in treating ulcerative colitis compared to mesalamine alone, with better outcomes observed in both short-term (≤8 weeks) and long-term (>8 weeks) treatments.

The combination treatment does not increase the risk of adverse events, indicating that it is both effective and safe for patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Mesalamine and Probiotics in Mild-to-Moderate Ulcerative Colitis: A Systematic Review and Meta-Analysis. Tian, C., Huang, Y., Wu, X., et al.[2022]

Current standard therapies for inflammatory bowel diseases (IBD) are effective for some patients but often lead to severe side effects and only induce sustained remission in a minority of cases.

Emerging treatments that manipulate the gut microbiota, such as rationally designed oral biotherapeutic products (LBPs) and fecal microbiota transplants, show promise in improving IBD outcomes and may serve as safer alternatives or adjuncts to traditional immunosuppressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbial-Based and Microbial-Targeted Therapies for Inflammatory Bowel Diseases. Oka, A., Sartor, RB.[2023]

In a real-world study of 41 steroid-dependent ulcerative colitis patients receiving fecal microbiota transplantation (FMT), 46.3% achieved steroid-free clinical remission after 24 weeks, demonstrating FMT's efficacy in this population.

The treatment was well-tolerated, with no serious adverse events leading to discontinuation, indicating that FMT is a safe option for managing steroid-dependent ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis. Sood, A., Mahajan, R., Juyal, G., et al.[2021]

Current treatments for inflammatory bowel disease (IBD) primarily focus on reducing inflammation but many patients do not respond or become resistant, highlighting the need for new therapies.

Fecal microbiota transplant (FMT) shows promise as a potential treatment for IBD by addressing gut microbiota imbalances, but more research is needed to determine the best methods for administration and donor matching.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplant - a new frontier in inflammatory bowel disease. Sunkara, T., Rawla, P., Ofosu, A., et al.[2023]

This case series is the first to show that fecal microbiota transplantation can effectively treat colitis associated with immune checkpoint inhibitors, suggesting a new therapeutic approach.

The treatment led to a reconstitution of the gut microbiome and an increase in regulatory T-cells in the colon, indicating that modifying the gut microbiome may help alleviate inflammation caused by immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. Wang, Y., Wiesnoski, DH., Helmink, BA., et al.[2022]

In a double-blind trial involving 81 patients with active ulcerative colitis, fecal microbiota transplantation (FMT) significantly increased microbial diversity and altered gut composition, which was linked to remission in patients.

Specific bacteria such as Eubacterium hallii and Roseburia inulivorans were associated with successful remission, while other bacteria like Fusobacterium gonidiaformans were linked to treatment failure, suggesting that understanding these microbial factors could enhance future therapies for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis. Paramsothy, S., Nielsen, S., Kamm, MA., et al.[2019]

The gut microbiome plays a significant role in inflammatory bowel disease (IBD), but no single microorganism has been identified as the main cause of the disease, indicating a complex interplay of factors.

Fecal microbial transplantation (FMT) shows promise in improving remission rates in ulcerative colitis, although current studies are limited by small sample sizes and varying methods, suggesting a need for more robust research to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Gut Microbiome as a Target for IBD Treatment: Are We There Yet? Knox, NC., Forbes, JD., Van Domselaar, G., et al.[2020]

The study found that patients with microscopic colitis (MC) had a significantly different microbiome composition compared to healthy controls, with lower bacterial diversity before treatment.

Treatment with budesonide improved the microbiome composition in MC patients, increasing diversity and moving it closer to that of healthy individuals, indicating a potential therapeutic effect on gut microbiota.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide. Rindom Krogsgaard, L., Kristian Munck, L., Bytzer, P., et al.[2020]

Patients with ulcerative colitis (UC) have a significantly less rich and diverse intestinal microbiota compared to healthy individuals, indicating a potential link between microbiota composition and UC severity.

In patients with active UC, there are notable increases in potentially harmful bacteria and decreases in beneficial butyrate-producing bacteria, suggesting that these microbial changes could serve as biomarkers for disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Composition and diverse differences of intestinal microbiota in ulcerative colitis patients. Zhu, S., Han, M., Liu, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study. [2021]

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

Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor-induced colitis. [2023]

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

Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Microbial Butyrate Synthesis Indicates Therapeutic Efficacy of Azathioprine in IBD Patients. [2021]

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

Microbiome-Based Biomarkers for IBD. [2021]

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

The Efficacy and Safety of Mesalamine and Probiotics in Mild-to-Moderate Ulcerative Colitis: A Systematic Review and Meta-Analysis. [2022]

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

Microbial-Based and Microbial-Targeted Therapies for Inflammatory Bowel Diseases. [2023]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplant - a new frontier in inflammatory bowel disease. [2023]

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

Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. [2022]

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

Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis. [2019]

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

The Gut Microbiome as a Target for IBD Treatment: Are We There Yet? [2020]

13. England pubmed.ncbi.nlm.nih.gov

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide. [2020]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Composition and diverse differences of intestinal microbiota in ulcerative colitis patients. [2022]