Fluconazole + IL-23 Therapy for Crohn's Disease
(FUN-CD Trial)
Recruiting in Palo Alto (17 mi)
Overseen byRandy Longman, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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)
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
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.
What data supports the effectiveness of the drug Fluconazole + IL-23 Therapy for Crohn's Disease?
Research shows that targeting IL-23, a part of the immune system, is effective for treating Crohn's disease. Drugs like risankizumab, which block IL-23, have shown promising results in clinical trials for Crohn's disease, suggesting that therapies targeting IL-23 can be beneficial.
12345Is IL-23 therapy safe for treating 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 studies indicating it is generally safe for human use.
13467How is the Fluconazole + IL-23 therapy different from other Crohn's disease treatments?
The Fluconazole + IL-23 therapy is unique because it combines an antifungal medication, Fluconazole, with a focus on blocking IL-23, a protein involved in the immune response that contributes to Crohn's disease. This approach is different from traditional treatments that often target broader immune pathways, as it specifically aims to inhibit the IL-23 pathway, which has shown promise in treating other immune-related conditions.
12348Eligibility Criteria
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
My Crohn's disease is mild to moderate.
I've been on a steady dose of my IBD medication for at least 4 weeks.
I am 18 years old or older.
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.
+6 more
Trial Timeline
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
Participant Groups
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).
2Treatment groups
Experimental Treatment
Placebo Group
Group I: IL-23 Therapy with FluconazoleExperimental Treatment2 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 PlaceboPlacebo Group2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Weill Cornell MedicineNew York, NY
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Who Is Running the Clinical Trial?
Weill Medical College of Cornell UniversityLead Sponsor
The Leona M. and Harry B. Helmsley Charitable TrustCollaborator
References
Efficacy and Safety of IL-12/23 and IL-23 Inhibitors for Crohn's Disease: Systematic Review and Meta-Analysis. [2023]Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn's disease (CD).
IL12/23 or selective IL23 inhibition for the management of moderate-to-severe Crohn's disease? [2019]The interleukin (IL)-12 family of cytokines, including IL12 and IL 23, play an important role in driving aberrant Th1 and Th17 immune responses in patients with Crohn's disease (CD). Targeting this pathway has opened new avenues for therapeutic intervention. The approval of ustekinumab, a monoclonal antibody blocking the common p40 subunit of IL12 and IL23, marked an important evolution in medical management for CD: this novel class of biologic therapy demonstrated efficacy in both patients naïve to biologics as well as in patients experiencing inadequate response or loss of response to TNF antagonists. However, as our understanding of the IL12/23 pathway has evolved, specific targeting of IL23 through its unique p19 subunit has become a focus for novel therapeutic development. IL23p19 antagonists have been shown in head-to-head trials to have superior efficacy to ustekinumab for other immune-mediated conditions such as psoriasis. In CD, phase II trials of monoclonal antibodies targeting IL23, including risankizumab and brazikumab, have shown promising results, with multiple agents now entering phase II or phase III studies. In this review, we summarize the current evidence for both anti-IL12/23p40 and anti-IL23p19 monoclonal antibodies in CD.
Blockade of IL-23: What is in the Pipeline? [2022]Interleukin 23 [IL-23] plays a key role in the pathogenesis of both Crohn's disease [CD] and ulcerative colitis [UC], promoting a Th17 cell-related immune response. The combined blockade of IL-23 and IL-12 with ustekinumab has been demonstrated to be safe and effective in the treatment of inflammatory bowel disease [IBD]. Studies on preclinical models and observations of other immune-mediated diseases, such as psoriasis, suggest that the selective inhibition of IL-23 could be beneficial in IBD. Four monoclonal antibodies [risankizumab, mirikizumab, brazikumab and guselkumab] are currently in advance clinical trials for either CD or UC. In this review, we provide an overview of the main results from published studies of selective anti IL-23 agents.
Targeting IL-23 for IBD: Rationale and Progress to Date. [2023]Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, comprises multiple complex immune-mediated disorders. Early diagnosis and prompt disease control may prevent long-term complications and hospitalization. The therapeutic options have expanded in the last two decades, with the development of biologics and small molecules targeting specific pathways implicated in inflammatory bowel disease pathogenesis. The interleukin (IL)-23/Th-17 axis is one such example. Targeting IL-12/23 is effective for the treatment of both moderate-to-severe Crohn's disease and ulcerative colitis, and ustekinumab (an IL-12/23p40 antagonist) is approved for both indications. In patients with psoriasis, improved clinical outcomes were observed with agents that more selectively targeted IL-23 (IL-23p19 antagonists) compared with those that target both IL-12 and IL-23. Many specific IL-23p19 antagonists are currently being investigated in Crohn's disease and ulcerative colitis, and risankizumab has been recently approved for moderate-to-severely active Crohn's disease. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of IL-23p19 antagonists for the treatment of inflammatory bowel disease.
Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study. [2022]Risankizumab, an anti-interleukin 23 antibody, was superior to placebo in achieving clinical and endoscopic remission at week 12 in a randomised, phase 2 induction study in patients with moderately to severely active Crohn's disease. Here we aimed to assess the efficacy and safety of extended intravenous induction and subcutaneous maintenance therapy with risankizumab.
Anti-interleukin-23 agents for the treatment of ulcerative colitis. [2020]Introduction: Treatment of ulcerative colitis (UC) aims to control symptoms and to suppress intestinal inflammation. Despite considerable advances, a proportion of patients do not respond to currently available drugs. The interleukin (IL)-23 axis plays a significant role in the pathogenesis of UC and has thus become an important target for drug development.Areas covered: The review briefly summarizes the pathophysiology of the IL-12/23 axis and provides a synopsis of the available evidence for efficacy and safety of ustekinumab, mirikizumab (LY3074828), risankizumab (BI655066/ABBV066), brazikumab (MEDI2070; formerly AMG139) and guselkumab (CNTO1959) in UC. We also provide an overview of ongoing and anticipated trials in this field.Expert opinion: A Phase 2 trial with mirikizumab and a Phase 3 trial with ustekinumab have demonstrated the efficacy of anti-IL-23 agents in achieving clinical and endoscopic outcomes in UC with a favorable safety profile. Trials of other anti-IL-23 agents in UC are under way and designed to explore head-to-head efficacy with existing biologics, as well as the prospect of combination biological therapy. Apart from data on longer term efficacy and safety, future trials should also explore strategies to inform the positioning of IL-23 antagonists in therapeutic algorithms.
Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study. [2022]Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn's disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study.
Investigational drugs in phase I and phase II clinical trials targeting interleukin 23 (IL23) for the treatment of Crohn's disease. [2020]Introduction: Medical therapy for Crohn's disease (CD) is directed at controlling intestinal inflammation to prevent development of disease-related complications. Not all patients will respond to currently available treatments and thus, novel therapies are needed. The interleukin (IL)-23 cytokine axis is implicated in CD pathogenesis and so targeting this pathway has become an important focus for drug development.Areas covered: This review summarizes the role of the IL23 cytokine pathway in CD pathogenesis and appraises phase I and II clinical trial data for novel IL23p19 specific monoclonal antibodies for the treatment of CD. The evidence for risankizumab (BI655066/ABBV066), brazikumab (MEDI2070, formerly AMG139), guselkumab (CNTO1959), tildrakizumab (MK3222), and mirikizumab (LY3074828) is reviewed; moreover, future applications for these agents are considered.Expert opinion: Targeting the specific p19 subunit of IL23 is a promising strategy in CD. Two multicenter, randomized, placebo-controlled phase II clinical trials have evaluated risankizumab and brazikumab. Both studies indicate that IL23-specific blockade is likely to be a safe and effective alternative to current biologics, including the TNF antagonists vedolizumab and ustekinumab. Confirmatory Phase 3 studies are underway. Ultimately, comparative effectiveness trials will be necessary to define the role of IL23-specific antagonists in CD treatment algorithms.