Fluconazole + IL-23 Therapy for Crohn's Disease

(FUN-CD Trial)

Overseen By Caroline Ericsson, BS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Weill Medical College of Cornell University

Must be taking: Fluconazole

Must not be taking: Antibiotics, Antifungals, QTc-prolonging drugs

Disqualifiers: Hepatic disease, Pregnancy, Severe Crohn's, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 27

Duration: 2 weeks

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current medications for at least 4 weeks before starting the treatment. However, you cannot participate if you are taking medications that interact with fluconazole and cause serious side effects.

What data supports the effectiveness of the drug Fluconazole + IL-23 Therapy for Crohn's Disease?

Research shows that targeting IL-23, a part of the immune system, is effective for treating Crohn's disease. Drugs like risankizumab, which block IL-23, have shown promising results in clinical trials for Crohn's disease, suggesting that therapies targeting IL-23 can be beneficial. ^{1 2 3 4 5}

Is IL-23 therapy safe for treating Crohn's disease?

IL-23 therapy, including drugs like risankizumab, has shown a favorable safety profile in treating Crohn's disease and other inflammatory conditions, with studies indicating it is generally safe for human use. ^{1 3 4 6 7}

How is the Fluconazole + IL-23 therapy different from other Crohn's disease treatments?

The Fluconazole + IL-23 therapy is unique because it combines an antifungal medication, Fluconazole, with a focus on blocking IL-23, a protein involved in the immune response that contributes to Crohn's disease. This approach is different from traditional treatments that often target broader immune pathways, as it specifically aims to inhibit the IL-23 pathway, which has shown promise in treating other immune-related conditions. ^{1 2 3 4 8}

What is the purpose of this trial?

The goal of this clinical trial is to learn about the effects of fluconazole in patients who plan to start or are currently undergoing standard of care treatment and plan to dose-escalate an IL-23 therapy for their Crohn's disease. The main question it aims to assess is whether or not patient response to IL-23 therapies improve when simultaneously treated with fluconazole.

Research Team

Randy Longman, MD, PhD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for individuals with Crohn's Disease who are currently receiving or planning to start IL-23 therapy. Specific eligibility criteria were not provided, so it's important to contact the study organizers for detailed requirements.

Inclusion Criteria

My Crohn's disease is mild to moderate.

I've been on a steady dose of my IBD medication for at least 4 weeks.

Exclusion Criteria

Known allergy to fluconazole

I have not taken antibiotics in the last month.

I have symptoms caused by a narrowing in my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IL-23 therapy with either fluconazole or placebo for 14 days

2 weeks

1 visit (in-person) at Day 0

Post-Treatment Monitoring

Participants are monitored for disease activity and sample collection at multiple time points

12 weeks

Visits at Week 2, Week 8, and Week 12 post-treatment initiation

Follow-up

Participants are monitored for long-term safety and effectiveness

1 year

Visits at Week 24 and 1 year post-treatment initiation

Treatment Details

Interventions

• Fluconazole

Trial Overview The trial is testing whether taking an anti-fungal medication called fluconazole alongside standard IL-23 therapy improves outcomes in Crohn's disease compared to a placebo (a pill without active medicine).

Participant Groups

Group I: IL-23 Therapy with Fluconazole Experimental Treatment 2 Interventions

Fluconazole will be blindly administered as capsules for oral consumption. On the first day, 200 mg will be given. Subjects will then take 100 mg once daily for thirteen days.

Group II: IL-23 Therapy with Placebo Placebo Group 2 Interventions

Placebo will be blindly administered as capsules for oral consumption. On the first day, 200 mg will be given. Subjects will then take 100 mg once daily for thirteen days.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

The Leona M. and Harry B. Helmsley Charitable Trust

Collaborator

Trials

69

Recruited

101,000+

Findings from Research

Targeting interleukin-23 (IL-23) significantly improves clinical and endoscopic remission rates in patients with moderate-to-severe Crohn's disease, based on a systematic review of 18 trials involving 5561 participants.

The use of IL-23 inhibitors is associated with a lower risk of serious adverse events compared to placebo, indicating that these treatments are both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of IL-12/23 and IL-23 Inhibitors for Crohn's Disease: Systematic Review and Meta-Analysis. Vuyyuru, SK., Solitano, V., Hogan, M., et al.[2023]

Ustekinumab, a monoclonal antibody that blocks the common p40 subunit of IL-12 and IL-23, has been effective in treating Crohn's disease (CD) in both patients new to biologics and those who did not respond to TNF antagonists, marking a significant advancement in treatment options.

Newer monoclonal antibodies targeting the specific p19 subunit of IL-23, such as risankizumab and brazikumab, have shown promising results in phase II trials for CD, suggesting they may offer superior efficacy compared to ustekinumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL12/23 or selective IL23 inhibition for the management of moderate-to-severe Crohn's disease? Ma, C., Panaccione, R., Khanna, R., et al.[2019]

Interleukin 23 (IL-23) is crucial in causing inflammation in Crohn's disease and ulcerative colitis, and targeting it could improve treatment outcomes for these conditions.

Four monoclonal antibodies that selectively inhibit IL-23 are currently in advanced clinical trials for inflammatory bowel disease, showing promise as effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of IL-23: What is in the Pipeline? Parigi, TL., Iacucci, M., Ghosh, S.[2022]

Targeting the IL-23/Th-17 pathway with specific antagonists, such as risankizumab, has shown promise in treating moderate-to-severe Crohn's disease, with recent approval highlighting its efficacy.

Compared to broader IL-12/23 antagonists like ustekinumab, IL-23p19 antagonists may offer improved clinical outcomes, suggesting a more targeted approach could enhance treatment effectiveness for inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting IL-23 for IBD: Rationale and Progress to Date. Vuyyuru, SK., Shackelton, LM., Hanzel, J., et al.[2023]

In a study involving 108 patients with moderately to severely active Crohn's disease, extended intravenous treatment with risankizumab significantly improved clinical remission rates, with 53% of patients achieving remission by week 26 after 12 weeks of treatment.

Risankizumab was well tolerated, with most adverse events being mild or moderate, and it successfully maintained remission in 71% of patients at week 52, indicating its potential as a safe and effective long-term treatment option for Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study. Feagan, BG., Panés, J., Ferrante, M., et al.[2022]

Anti-IL-23 agents, such as mirikizumab and ustekinumab, have shown significant efficacy in treating ulcerative colitis (UC) in clinical trials, achieving both clinical and endoscopic improvements with a favorable safety profile.

Ongoing trials are exploring the effectiveness of various anti-IL-23 agents compared to existing treatments and investigating the potential for combination therapies, which could enhance treatment strategies for UC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-interleukin-23 agents for the treatment of ulcerative colitis. Hanžel, J., D'Haens, GR.[2020]

In a long-term study of 65 patients with moderate-to-severe Crohn's disease, risankizumab was well tolerated over a median of 33 months, with no new safety concerns and a low rate of serious adverse events (24.6 events/100 patient-years).

Efficacy was maintained throughout the study, with over 71% of patients achieving clinical remission and more than 42% achieving endoscopic remission, indicating that risankizumab remains effective for long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study. Ferrante, M., Feagan, BG., Panés, J., et al.[2022]

Targeting the IL-23 cytokine pathway, particularly the p19 subunit, shows promise as a safe and effective treatment for Crohn's disease, as indicated by phase I and II clinical trials of monoclonal antibodies like risankizumab and brazikumab.

Both multicenter, randomized, placebo-controlled trials for risankizumab and brazikumab suggest that these IL-23-specific therapies could serve as viable alternatives to existing biologics, with further phase 3 studies needed to confirm their effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational drugs in phase I and phase II clinical trials targeting interleukin 23 (IL23) for the treatment of Crohn's disease. Ma, C., Jairath, V., Khanna, R., et al.[2020]

References

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

Efficacy and Safety of IL-12/23 and IL-23 Inhibitors for Crohn's Disease: Systematic Review and Meta-Analysis. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

IL12/23 or selective IL23 inhibition for the management of moderate-to-severe Crohn's disease? [2019]

3. England pubmed.ncbi.nlm.nih.gov

Blockade of IL-23: What is in the Pipeline? [2022]

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

Targeting IL-23 for IBD: Rationale and Progress to Date. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Anti-interleukin-23 agents for the treatment of ulcerative colitis. [2020]

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

Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Investigational drugs in phase I and phase II clinical trials targeting interleukin 23 (IL23) for the treatment of Crohn's disease. [2020]