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
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 120
- Locations
- 2
- Primary Endpoint
- Proportion of subjects achieving clinical response
Study Overview
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), 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:
- IL-23 Therapy with Fluconazole (200 mg on Day 0 and 100 mg on Days 1-13)
- 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. They will have an ancillary visit at Weill Cornell or a local laboratory of their choosing 2 weeks post-treatment initiation. Subjects will also return for a standard of care clinic visit 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) and Week 12 post-treatment initiation. Subjects may also opt in to provide these samples at Week 2 post-treatment initiation and Week 8 post-treatment initiation. If subjects consent to biopsies, biopsies will also be collected for research at endoscopic procedures (colonoscopies and/or flexible sigmoidoscopies). Subjects may opt in to return at Week 24 and 1 year post-treatment initiation for standard of care visits, where blood, stool, and oral swabs would also be collected for research.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
Double-blinded study
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients at least 18 years old
- •Patients with mild to moderate Crohn's disease as defined by CDAI score of 150-450
Exclusion Criteria
- •Antifungal usage within one month prior to initiation of blinded fluconazole usage
- •Known allergy to fluconazole
- •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
- •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
- •Pregnant or lactating women
- •Severe Crohn's disease defined by a PRO-2 score ≥ 34 or imminent need for surgery, or deemed not medically fit by physician
- •Patient with symptomatic stricturing
- •Patient with pouchitis or an ostomy
- •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.
- •Patients with hypokalemia, or advanced cardiac failure
- •Patients with renal insufficiency
Arms & Interventions
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.
Intervention: IL-23 Therapy (Biological)
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.
Intervention: Placebo (Drug)
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.
Intervention: IL-23 Therapy (Biological)
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.
Intervention: Fluconazole (Drug)
Outcomes
Primary Outcomes
Proportion of subjects achieving clinical response
Time Frame: Week 12 post-Fluconazole Initiation
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.
Secondary Outcomes
- Proportion of subjects achieving clinical remission(Week 12 post-Fluconazole Initiation)
- Proportion of patients achieving endoscopic response or remission(Up to 1 Year post-Fluconazole Initiation)