Testing the Role for Anti-fungal Therapy in Improving the Response to Medicine for Crohn's Disease

Crohn's Disease Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06274554
• Other study ID #: 23-11026746
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: December 2029

Study information

• Verified date: February 2024
• Source: Weill Medical College of Cornell University
• Contact: Nancy Tran, BS
• Phone: 646-697-0985
• Email: nat4010[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to learn about the effects of fluconazole in patients who plan to or are undergoing standard of care treatment with an IL-23 therapy for their Crohn's disease.

The main question it aims to assess is will patient response to IL-23 therapies improve when simultaneously treated with fluconazole.

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). After Week 12, subjects will have the option to pursue open-label fluconazole treatment. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 2029
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. 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 treatment

2. Antifungal usage within one month prior to initiation of blinded fluconazole treatment

3. Known allergy to fluconazole

4. Patients with known hepatic disease or cirrhosis

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

6. Pregnant or lactating women

7. Severe Crohn's disease defined by a PRO-2 (2-item patient-reported outcome) score = 34 or imminent need for surgery, or deemed not medically fit by physician

8. Patient with symptomatic stricturing

9. Patient with pouchitis or an ostomy

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• Inflammatory Bowel Diseases

Intervention

Drug:
• Fluconazole
Oral fluconazole capsules.
• Placebo
Oral placebo capsules will be used as a comparator.

Biological:
• IL-23 Therapy
Risankizumab (IL-23) or Ustekinumab (IL-12/23) as standard of care treatment.

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	The Leona M. and Harry B. Helmsley Charitable Trust

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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