Posaconazole for Crohn's Disease

No longer recruiting at 1 trial location

Overseen By Melissa Hampton

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Statins, Sirolimus, Ergot alkaloids, others

Disqualifiers: Ulcerative colitis, Renal impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the oral antifungal posaconazole affects individuals with active Crohn's disease, particularly those with the CARD9 S12N risk allele, which may enhance immune responses. Researchers aim to determine if this treatment can reduce Crohn's disease activity and the presence of the yeast Malassezia in the gut. Participants will receive either posaconazole or a placebo (a pill with no active drug) for 12 weeks. Suitable candidates have had Crohn's disease for at least 6 months, experience active symptoms, and possess the specified genetic trait. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand its benefits for more patients.

Do I have to stop taking my current medications for the trial?

You can continue taking certain medications like oral aminosalicylates, immunomodulators, anti-TNF, anti IL12/23, anti-integrin therapy, and oral corticosteroids if they have been stable for a specified period before the trial. However, you cannot take medications primarily metabolized by CY3PA4, antibiotics, antifungal agents, probiotics, or prebiotics within two weeks of screening.

What is the safety track record for posaconazole?

Research has shown that posaconazole is commonly used to treat and prevent fungal infections, and studies have found it effective. Participants should know that posaconazole is usually well-tolerated, with most people experiencing only mild side effects like nausea, headache, or diarrhea.

Since this trial is in a later stage, posaconazole has already been tested on many people. This stage primarily evaluates its effectiveness and examines long-term use. As a result, extensive safety information is available about posaconazole. However, using it for Crohn's disease is new, making this trial crucial for understanding its effects on this specific condition. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for Crohn's disease, like biologics and immunosuppressants, aim to control inflammation by suppressing the immune system. But posaconazole works differently, targeting fungal infections that might be contributing to the disease's progression. Unlike typical options, posaconazole is an antifungal agent, not an immunosuppressant, which means it may offer relief without the side effects associated with weakening the immune system. Researchers are excited about this treatment because it represents a novel approach that could provide an alternative for patients who don't respond well to existing therapies.

What evidence suggests that posaconazole might be an effective treatment for Crohn's disease?

Research has shown that posaconazole effectively treats various fungal infections. It prevents and treats these infections in individuals with weakened immune systems, such as those with acute myeloid leukemia. However, strong evidence does not yet support posaconazole's effectiveness for Crohn's Disease. In this trial, participants will receive either posaconazole or a placebo to study its potential effects on Crohn's Disease, particularly in patients with a specific genetic risk factor. The medicine's ability to alter fungal levels and immune responses could potentially benefit these patients. ^{1 2 3 5 6}

Who Is on the Research Team?

Gil Y Melmed, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-60 with Crohn's Disease affecting the ileum/colon, carrying a specific genetic risk (CARD9 S12N allele), can join this trial. They must have stable disease treatments and agree to contraception if applicable. Excluded are those allergic to azoles, with severe colitis or organ issues, recent drug/alcohol abuse, or on certain medications.

Inclusion Criteria

I have active Crohn's disease confirmed by a scope test and symptoms.

I have a specific genetic variation linked to increased disease risk.

I have Crohn's disease affecting my ileum or colon for at least 6 months.

Exclusion Criteria

I am not taking drugs that are mainly processed by the liver enzyme CY3PA4.

I don't have any major health issues that would stop me from joining the study.

Alcohol or drug abuse (in the opinion of the Investigator) that would interfere with compliance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive posaconazole or placebo for 12 weeks to evaluate effects on Crohn's disease activity

12 weeks

1 visit (in-person) for initial dosing, followed by regular monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Matching Placebo Tablet
• Posaconazole

Trial Overview The study tests Posaconazole against a placebo in Crohn's patients with a genetic predisposition. It aims to see if the antifungal treatment reduces disease activity and immune responses by altering gut microbes associated with Malassezia spp.

How Is the Trial Designed?

Group I: Posaconazole Experimental Treatment 1 Intervention

Subjects administered posaconazole (Noxafil®, Merck) 300mg twice daily for 1 day followed by 300mg daily for 12 weeks

Group II: Placebo Placebo Group 1 Intervention

Subjects administered three matching placebo tablets twice daily for 1 day followed by three tablets daily for 12 weeks

Posaconazole is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Approved in United States as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Approved in Canada as Noxafil for:

• Invasive Aspergillus infections
• Candidemia
• Oropharyngeal Candidiasis

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 25 patients with aplastic anemia (AA), Danazol treatment significantly increased the percentage of T regulatory cells (T-regs), which are important for immune regulation, compared to baseline levels.

Danazol was found to be effective in raising T-reg levels in AA patients, showing a greater increase than standard immunosuppressive treatments, suggesting its potential role in improving immune function in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Danazol increases T regulatory cells in patients with aplastic anemia. Khurana, H., Malhotra, P., Sachdeva, MU., et al.[2018]

In a study of 79 patients with chronic aplastic anemia, the combination of Pai-Neng-Da Capsule (PNDC) with cyclosporine and androgen showed an effective rate of 88.1%, compared to 77.8% for the control group, indicating PNDC enhances treatment efficacy.

PNDC treatment resulted in significantly lower masculinization scores in female patients compared to the control group, suggesting it can reduce side effects associated with androgen therapy while maintaining therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study. Jiang, ZY., Yu, FQ., Gao, RL., et al.[2022]

Posaconazole is an orally active triazole antifungal that is currently undergoing phase III clinical trials for treating serious opportunistic fungal infections, such as aspergillosis and candidiasis.

In addition to its primary indications, preclinical studies suggest that posaconazole may also be effective against Cryptococcus neoformans, which causes cryptococcosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: SCH 56592. [2019]

A study using MRI on adult and juvenile Beagle dogs showed that the intravenous administration of posaconazole (Noxafil) did not affect brain ventricle volume over three months, indicating its safety regarding brain development in older dogs.

The research highlighted significant natural variability in brain ventricle sizes among dogs, which is important for accurately interpreting the effects of treatments like posaconazole and supports its potential use in children over two years of age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution. Hines, CD., Song, X., Kuruvilla, S., et al.[2015]

Posaconazole is an effective antifungal medication for preventing Candida and Aspergillus infections in immunocompromised patients, but it must be taken with food to ensure proper absorption and effectiveness.

In a case study of a 49-year-old woman with acute myeloid leukemia, failure to adhere to the recommended administration guidelines for posaconazole likely contributed to her severe invasive sinus infection and subsequent death, highlighting the critical need for patient education on medication use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breakthrough invasive fungal infection in an immunocompromised host while on posaconazole prophylaxis: an omission in patient counseling and follow-up. Kishel, JJ., Sivik, J.[2021]

Posaconazole demonstrated potent antifungal activity against a wide range of clinically important fungi, with MIC(50) and MIC(90) values of 0.063 microg/ml and 1 microg/ml, respectively, based on testing of approximately 19,000 strains across 45 laboratories.

It was particularly effective against resistant strains of Candida and Aspergillus spp., showing superior activity compared to other antifungal agents like itraconazole, fluconazole, and amphotericin B, making it a promising option for treating difficult fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Sabatelli, F., Patel, R., Mann, PA., et al.[2022]

In a study involving three patients with inflammatory bowel disease (IBD), the PSMA-targeted imaging agent [18F]DCFPyL successfully identified areas of active inflammation in the gastrointestinal tract, correlating with endoscopic and histological findings.

The results suggest that [18F]DCFPyL PET imaging could serve as a valuable non-invasive tool for assessing the location and extent of inflammation in IBD, potentially improving disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA-Targeted PET Radiotracer [18F]DCFPyL as an Imaging Biomarker in Inflammatory Bowel Disease. Ismail, MS., Peters, DE., Rowe, SP., et al.[2023]

Posaconazole is an effective antifungal agent approved for preventing and treating invasive fungal infections, particularly in patients with weakened immune systems, such as those undergoing stem cell transplants.

The new gastro-resistant tablet formulation of posaconazole offers significant pharmacokinetic advantages over the oral suspension, including improved absorption, less variability between patients, and the convenience of once-daily dosing, making it the preferred choice for optimizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections. McKeage, K.[2018]

Piflufolastat F 18 (PYLARIFY®) is a newly approved diagnostic imaging agent that targets prostate-specific membrane antigen (PSMA) for use in PET scans, specifically for detecting prostate cancer lesions.

Approved in the USA on May 27, 2021, Piflufolastat F 18 is intended for men with prostate cancer who have suspected metastasis or recurrence, providing a valuable tool for guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Piflufolastat F 18: Diagnostic First Approval. Keam, SJ.[2022]

In a study of 8 patients with Fanconi anemia (FA) treated with danazol, 7 patients showed significant improvements in hemoglobin and platelet counts, with increases of over 50% within 6 months, and these improvements were maintained for up to 3 years.

Danazol was well-tolerated, with no severe side effects leading to treatment discontinuation, suggesting it could be a safe and effective option for managing bone marrow failure in FA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of the bone marrow failure in Fanconi anemia patients with danazol. Scheckenbach, K., Morgan, M., Filger-Brillinger, J., et al.[2013]

In a study of 76 patients with chronic aplastic anemia, the combination of compound Zaofan pill with cyclosporine and androgen resulted in a significantly higher cure and response rate (44.7%) compared to cyclosporine and androgen alone (15.8%).

The treatment with compound Zaofan pill also led to a notable increase in bone marrow microvessel density (MVD) and vascular endothelial growth factor (VEGF) levels, suggesting that it enhances the bone marrow environment, which is crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of Compound Zaofan Pill on Bone Marrow MVD and VEGF of Patients with Chronic Aplastic Anemia]. Yang, FF., Wang, KW., Xiang, Q., et al.[2018]

In a phase I study involving 23 advanced-stage cancer patients, vorinostat was found to be safe and tolerable, with common side effects including mild to moderate nausea and fatigue.

The study revealed that a high-fat meal slightly increased the absorption of vorinostat but did not significantly impact its overall effectiveness, suggesting that vorinostat can be administered with or without food in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study to determine the effects of food and multiple dosing on the pharmacokinetics of vorinostat given orally to patients with advanced cancer. Rubin, EH., Agrawal, NG., Friedman, EJ., et al.[2018]

In a study of 18 patients with active ulcerative colitis (UC), single-needle granulocyte monocyte adsorption (SN-GMA) treatment led to a significantly higher clinical remission rate in patients who had not previously used corticosteroids (90.9%) compared to those who had (42.9%).

The study also found that SN-GMA was more effective in removing leukocytes and granulocytes from the blood in corticosteroid-naïve patients, suggesting that SN-GMA may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis. Noguchi, Y., Shimazu, K., Totani, T., et al.[2023]

The novel [18F]AlF-PSMA-137 probe demonstrated high specificity and binding affinity to prostate-specific membrane antigen (PSMA), with a radiochemical purity over 99% and effective tumor imaging capabilities in both preclinical and clinical settings.

In a pilot study involving 13 patients, [18F]AlF-PSMA-137 successfully detected 81 lesions, showing significant increases in tumor uptake over time, indicating its potential as an effective tool for diagnosing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation and first in human study of Al18F radiolabeled ODAP-urea-based PSMA targeting ligand for PET imaging of prostate cancer. Ren, Y., Liu, C., Liu, T., et al.[2022]

Flotufolastat F 18 (POSLUMA®) is a newly approved imaging agent specifically designed for detecting prostate cancer lesions using PET scans, particularly in men with suspected metastasis or recurrence.

The approval in May 2023 marks a significant milestone in prostate cancer diagnostics, allowing for better identification of PSMA positive lesions in patients who are candidates for definitive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flotufolastat F 18: Diagnostic First Approval. Heo, YA.[2023]

Citations

1. withpower.com withpower.com/trial/phase-4-crohn-disease-8-2021-929ba

Posaconazole for Crohn's Disease · Info for Participants The available research does not provide any data supporting the effectiveness of Posaconazole for Crohn's Disease. The articles focus on other treatments and ...

2. aging.networkofcare.org aging.networkofcare.org/riverside/CommunityResources/ClinicalTrials/Detail/NCT04966585?keyword=%22CARD9%22

Pilot Study of Posaconazole in Crohn's Disease This trial is designed to evaluate the effects of oral antifungal treatment with posaconazole on active Crohn's disease (CD) activity and the burden of ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12848593/

Posaconazole: SCH 56592 Posaconazole [SCH 56592, SPRIAFIL, Noxafil] is an orally active triazole derivative that is in phase III trials with the Schering-Plough Research Institute ...

4. ctv.veeva.com ctv.veeva.com/study/pilot-study-of-posaconazole-in-crohns-disease

Pilot Study of Posaconazole in Crohn's Disease This trial is designed to evaluate the effects of oral antifungal treatment with posaconazole on active Crohn's disease (CD) activity and ...

5. clinicaltrials.eu clinicaltrials.eu/inn/posaconazole/

Posaconazole: A Comprehensive Guide for Patients Clinical trials have shown posaconazole to be effective in preventing and treating various fungal infections. For example: In patients with acute myeloid ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05275179

NCT05275179 No information is available for this page.