Fluconazole + IL-23 Therapy for Crohn's Disease

(FUN-CD Trial)

Overseen By Aurelia Li, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding fluconazole, a common antifungal medication, can enhance the effectiveness of IL-23 therapy for people with Crohn's disease. Researchers aim to determine if combining these treatments improves patient outcomes compared to using IL-23 therapy alone. Participants will receive either fluconazole or a placebo (a dummy pill) alongside their IL-23 therapy. Individuals with mild to moderate Crohn's disease who haven't recently used antifungal treatments might be suitable for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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.

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

Research has shown that IL-23 therapies, such as those used for Crohn's disease, are generally safe and well-tolerated. These therapies are already used for other inflammatory conditions, suggesting their safety for patients.

Fluconazole, a medication for fungal infections, has FDA approval, indicating it has been tested and found safe for use in people.

Researchers are studying the combination of fluconazole with IL-23 therapy to determine if it improves treatment outcomes. The current study phase suggests there is sufficient safety information to test this combination in more people. However, like any treatment, risks may exist, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Crohn's disease?

Unlike the standard treatments for Crohn's disease, which often include anti-inflammatory drugs or immunosuppressants, this new therapy combines Fluconazole with IL-23 blockade. Fluconazole, primarily an antifungal agent, is being repurposed here to potentially enhance immune modulation. Researchers are excited because this combination targets IL-23, a protein that plays a critical role in the inflammation process of Crohn's disease, offering a novel approach that could lead to more effective and faster relief of symptoms. By addressing a different pathway than typical therapies, this treatment could offer hope to patients who have not responded well to conventional options.

What evidence suggests that this trial's treatments could be effective for Crohn's disease?

Studies have shown that IL-23 therapies, such as risankizumab, effectively treat Crohn's disease. In earlier trials, these treatments significantly improved symptoms in about 45% of patients. In this trial, researchers are examining the effects of IL-23 therapy using two different approaches. One group will receive IL-23 therapy with fluconazole, an antifungal drug, to determine if it enhances the treatment's effectiveness. The other group will receive IL-23 therapy with a placebo. The hypothesis is that reducing fungi might help the body respond more effectively to the IL-23 treatment. While IL-23 therapies already show promise, researchers hope that combining them with fluconazole could lead to even better patient outcomes. ^{1 3 6 7 8}

Who Is on the Research Team?

Randy Longman, MD, PhD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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

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

My Crohn's disease is mild to moderate.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06274554

NCT06274554 | Testing the Role of Anti-fungal Therapy in ... The purpose of this study is to examine the efficacy and safety of fluconazole in combination with IL-23 therapy versus IL-23 therapy alone for the treatment of ...

2. withpower.com withpower.com/trial/phase-3-inflammatory-bowel-diseases-5-2024-bde47

Fluconazole + IL-23 Therapy for 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12030181/

New Interleukin-23 Antagonists' Use in Crohn's Disease - PMC Risankizumab showed favorable results in pivotal trials like ADVANCE, MOTIVATE, and FORTIFY, achieving remission rates of up to 45% and ...

4. medrxiv.org medrxiv.org/content/10.1101/2025.09.03.25334996v1.full-text

Efficacy and Safety of IL-23 Inhibitors in the Treatment ... This analysis highlights Mirikizumab as the most effective IL-23 inhibitor for inducing endoscopic remission in Crohn's disease, followed by ...

5. reports.mountsinai.org reports.mountsinai.org/article/gi2026-crohns-clinical-trials

New IL-23 Inhibitors Expand Treatment Options for Crohn's ... In the trials, both drugs clearly demonstrated superiority over placebo, with some patients in each trial achieving clinical remission. The trials also compared ...

6. trialx.com trialx.com/clinical-trials/listings/307011/testing-the-role-of-anti-fungal-therapy-in-improving-the-response-to-therapies-for-crohns-disease/

Testing the Role of Anti-fungal Therapy in Improving ... The purpose of this study is to examine the efficacy and safety of fluconazole in combination with IL-23 therapy versus IL-23 therapy alone for ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/463897

Testing the Role of Anti-fungal Therapy in Improving ... The main question it aims to assess is whether or not patient response to IL-23 therapies improve when simultaneously treated with fluconazole.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11193621/

Low Incidence of Invasive Fungal Infections in a Large ... We found higher IFI incidence in IL-17 and IL-23 inhibitor patients receiving corticosteroids and in IL-23 inhibitor patients with Crohn's ...