Clinical trial NCT06274554: Testing the Role of Anti-fungal Therapy in Improving the Response to Therapies for Crohn's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Crohn's Disease
Inflammatory Bowel Diseases
Keywords: Fluconazole
IL-23
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: The Leona M. and Harry B. Helmsley Charitable Trust
First posted: 2024-02-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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) or risankizumab (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 and blood 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 and stool will also be collected for research.

Eligibility criteria: 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
3. Besides the biologics of interest in this study, subjects must be on stable dosing of any therapy for at least 4 weeks prior to treatment initiation. Including:

   1. Steroids (9 mg or less of budesonide, 20 mg or less of prednisone)
   2. Mesalamines
   3. Immunomodulators
   4. Biologics
   5. Other medications for IBD (inflammatory bowel disease)

Exclusion Criteria:

1. Antibiotic usage within one month prior to initiation of blinded fluconazole usage
2. Antifungal usage within one month prior to initiation of blinded fluconazole usage
3. Known allergy to fluconazole
4. 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
5. Patients taking medications known to interact with fluconazole and cause serious adverse events, including but not limited to death, cardiac events, serious cardiac dysrhythmias, and prolongation of QTc (corrected QT interval)
6. Pregnant or lactating women
7. Severe Crohn's disease defined by a PRO-2 score ≥ 34 (patient reported outcomes) or imminent need for surgery, or deemed not medically fit by physician
8. Patient with symptomatic stricturing
9. Patient with pouchitis or an ostomy
10. Patients with known, active fungal, or other, 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.
11. Patients with hypokalemia, or advanced cardiac failure
12. Patients with renal insufficiency

Primary outcomes:
measure: Proportion of subjects achieving clinical response
timeFrame: Week 12 post-Fluconazole Initiation
Secondary outcomes:
measure: Proportion of subjects achieving clinical remission
timeFrame: Week 12 post-Fluconazole Initiation
measure: Proportion of patients achieving endoscopic response or remission
timeFrame: Up to 1 Year post-Fluconazole Initiation
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Randy Longman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: