Testing the Role of Anti-fungal Therapy in Improving the Response to Therapies for Crohn's Disease (FUN-CD)

A Prospective, Randomized, Placebo-controlled Trial of Fluconazole in Combination With IL-23 Therapy Versus IL-23 Therapy Alone for the Treatment of Crohn's Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases; Crohn's Disease
• Intervention / Treatment: Drug: Fluconazole; Drug: Placebo; Biological: IL-23 Therapy

Detailed Description

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 Crohn's disease (CD). IL-23 therapy may include ustekinumab (anti-interleukin-12/23), risankizumab (anti-interleukin-23), or guselkumab (anti-interleukin-23).

Subjects will be stratified into two groups based on standard of care treatment: IL-23 therapy initiation or IL-23 therapy dose escalation. Subjects in each group will then be randomized to one of two treatment arms:

1. IL-23 Therapy with Fluconazole (200 mg on Day 0 and 100 mg on Days 1-13)
2. IL-23 Therapy with Placebo (200 mg on Day 0 and 100 mg on Days 1-13)

Subjects will blindly receive the fluconazole treatment only if they meet all inclusion and exclusion criteria. Subjects will return for standard of care clinic visits 2 weeks post-treatment initiation and 12 weeks post-treatment initiation. Disease activity will be assessed at standard of care visits. Stool, blood, and oral swab samples will collected for research from subjects at Day 0 (pre-treatment initiation), Week 2 post-treatment initiation, Week 8 post-treatment initiation, and Week 12 post-treatment initiation. If subjects consent to biopsies, biopsies will also be collected for research at endoscopic procedures (colonoscopies and/or flexible sigmoidoscopies). Subjects will return at Week 24 and 1 year post-treatment initiation for standard of care visits, where blood, stool, and oral swabs will also be collected for research.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Caroline Ericsson, BS; Phone Number: 646-697-0985; Email: cae4007@med.cornell.edu
• Study Contact Backup: Name: Aurelia Li, BS; Phone Number: 646-697-0985; Email: aul4004@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
      • Sub-Investigator: Dana Lukin, MD, PhD
      • Principal Investigator: Randy Longman, MD, PhD
      • Sub-Investigator: Ellen Scherl, MD
      • Principal Investigator: Iliyan Iliev, PhD
      • Contact: Caroline Ericsson, BS; Phone Number: 646-697-0985; Email: cae4007@med.cornell.edu
      • Contact: Aurelia Li; Email: aul4004@med.cornell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients at least 18 years old
2. Patients with mild to moderate Crohn's disease as defined by CDAI score of 150-450

Exclusion Criteria:

1. Antifungal usage within one month prior to initiation of blinded fluconazole usage
2. Known allergy to fluconazole
3. Patients with known hepatic disease, cirrhosis, or with elevated liver biochemistries (e.g., transaminase(s) >3X upper limit of normal (ULN), and/or bilirubin levels >1.5X ULN (with exception of confirmed Gilbert's disease) at baseline
4. Patients taking any medications judged by clinical provider to interact with fluconazole and are known contraindications (refer to section 2.2) and cause serious adverse events, including but not limited to death, cardiac events, serious cardiac dysrhythmias, and prolongation of QTc
5. Pregnant or lactating women
6. Severe Crohn's disease defined by a PRO-2 score ≥ 34 or imminent need for surgery, or deemed not medically fit by physician
7. Patient with symptomatic stricturing
8. Patient with pouchitis or an ostomy
9. Patients with known, active fungal infection(s) since these patients would require particular, standard-of-care monitoring and treatment, which may include intravenous and/or prolonged courses of fluconazole or other therapies.
10. Patients with hypokalemia, or advanced cardiac failure
11. Patients with renal insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IL-23 Therapy with Fluconazole; 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.	Drug: Fluconazole; Oral fluconazole capsules.; Other Names: Diflucan; Biological: IL-23 Therapy; Risankizumab (IL-23), Guselkumab (IL-23), or Ustekinumab (IL-12/23) as standard of care treatment.; Other Names: Ustekinumab; Risankizumab; Guselkumab
Placebo Comparator: IL-23 Therapy with Placebo; 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.	Drug: Placebo; Oral placebo capsules will be used as a comparator.; Biological: IL-23 Therapy; Risankizumab (IL-23), Guselkumab (IL-23), or Ustekinumab (IL-12/23) as standard of care treatment.; Other Names: Ustekinumab; Risankizumab; Guselkumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving clinical response	Participants with clinical response are those participants with a reduction of the Crohn's Disease Activity Index (CDAI) by 100 or more points from baseline at week 12 post-Fluconazole initiation.	Week 12 post-Fluconazole Initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving clinical remission	Participants achieving clinical remission are those participants with a Crohn's Disease Activity Index (CDAI) score of no greater than 150 points at week 12 post-Fluconazole initiation.	Week 12 post-Fluconazole Initiation
Proportion of patients achieving endoscopic response or remission	Participants achieving endoscopic response are those participants with a reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD) of at least 50% from baseline. Participants achieving endoscopic remission are those participants with an SES-CD score less than or equal to 2	Up to 1 Year post-Fluconazole Initiation

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: The Leona M. and Harry B. Helmsley Charitable Trust
• Investigators: Principal Investigator: Randy Longman, MD, PhD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 15, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Fluconazole; IL-23
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Crohn Disease; Inflammatory Bowel Diseases; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Triazoles; Ustekinumab; Fluconazole; guselkumab; risankizumab
• Other Study ID Numbers: 23-11026746

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes