Posaconazole for Crohn's Disease

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

10 Participants Needed

Trial Summary

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 data supports the idea that Posaconazole for Crohn's Disease is an effective drug?

The available research does not provide any data supporting the effectiveness of Posaconazole for Crohn's Disease. The articles focus on other treatments and diagnostic agents for different conditions, such as prostate cancer and ulcerative colitis, but do not mention Posaconazole or its impact on Crohn's Disease. ^{1 2 3 4 5}

What safety data is available for Posaconazole?

Posaconazole, also known as Noxafil, is a triazole antifungal agent with an established safety profile for the treatment and prophylaxis of invasive fungal infections. It is approved for use in adults and has been studied in various formulations, including oral suspension, gastro-resistant tablets, and intravenous solutions. The drug is generally well-tolerated, but proper administration is crucial to avoid subtherapeutic levels, as highlighted by a case where improper use led to treatment failure. Posaconazole has been shown to be effective against a wide range of fungal pathogens, often outperforming other antifungal agents in vitro. ^{6 7 8 9 10}

Is the drug Posaconazole a promising treatment for Crohn's Disease?

The provided research articles do not contain information about Posaconazole or its effects on Crohn's Disease, so we cannot determine if it is a promising treatment based on this data. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial is testing an oral antifungal medication to help Crohn's disease patients with a specific genetic marker. The medication aims to reduce a type of fungus in the body, which may calm the immune system and improve symptoms.

Research Team

Gil Y Melmed, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Piflufolastat F 18: Diagnostic First Approval. [2022]

2. Switzerland 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. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

PSMA-Targeted PET Radiotracer [18F]DCFPyL as an Imaging Biomarker in Inflammatory Bowel Disease. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Flotufolastat F 18: Diagnostic First Approval. [2023]

5. England 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. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Posaconazole: SCH 56592. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

8. United States 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. [2015]

9. England 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. [2021]

10. United States 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. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Treatment of the bone marrow failure in Fanconi anemia patients with danazol. [2013]

12. China pubmed.ncbi.nlm.nih.gov

[Effect of Compound Zaofan Pill on Bone Marrow MVD and VEGF of Patients with Chronic Aplastic Anemia]. [2018]

13. United States 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. [2018]

14. England pubmed.ncbi.nlm.nih.gov

Danazol increases T regulatory cells in patients with aplastic anemia. [2018]

15. China 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. [2022]