Posaconazole for Crohn's Disease
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen ByGil Y Melmed, MD
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Waitlist Available
Sponsor: Cedars-Sinai Medical Center
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
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.
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.
12345What 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.
678910Eligibility 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 am 18 years old or older.
I have a specific genetic variation linked to increased disease risk.
+6 more
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
+8 more
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: PosaconazoleExperimental Treatment1 Intervention
Subjects administered posaconazole (Noxafil®, Merck) 300mg twice daily for 1 day followed by 300mg daily for 12 weeks
Group II: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo ClinicRochester, MN
Cedars-Sinai Medical Center (CSMC)Los Angeles, CA
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Who Is Running the Clinical Trial?
Cedars-Sinai Medical CenterLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
Piflufolastat F 18: Diagnostic First Approval. [2022]Piflufolastat F 18 (PYLARIFY®) is an 18F-labelled diagnostic imaging agent that has been developed by Progenics Pharmaceuticals Inc., a Lantheus company, for positron emission tomography (PET) that targets prostate-specific membrane antigen (PSMA). Piflufolastat F 18 was approved in the USA on 27 May 2021 for PET of PSMA positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate specific antigen (PSA) level. This article summarizes the milestones in the development of piflufolastat F 18 leading to this approval as a radioactive diagnostic agent in prostate cancer.
Preclinical evaluation and first in human study of Al18F radiolabeled ODAP-urea-based PSMA targeting ligand for PET imaging of prostate cancer. [2022]Label="Purpose" NlmCategory="UNASSIGNED">This study aimed to introduce a novel [18F]AlF-labeled ODAP-Urea-based Prostate-specific membrane antigen (PSMA) probe, named [18F]AlF-PSMA-137, which was derived from the successful modification of glutamate-like functional group. The preclinically physical and biological characteristics of the probe were analyzed. Polit clinical PET/CT translation was performed to analyze its feasibility in clinical diagnosis of prostate cancer.
PSMA-Targeted PET Radiotracer [18F]DCFPyL as an Imaging Biomarker in Inflammatory Bowel Disease. [2023]Label="Background" NlmCategory="UNASSIGNED">Prostate-specific membrane antigen (PSMA) is highly and specifically upregulated in active-inflamed mucosa of patients with inflammatory bowel disease (IBD). We hypothesized that this upregulation would be detectable using a PSMA-targeted positron emission tomography/computed tomography (PET/CT) imaging agent, [18F]DCFPyL, enabling non-invasive visualization of inflammation. A noninvasive means of detecting active inflammation would have high clinical value in localization and management of IBD.
Flotufolastat F 18: Diagnostic First Approval. [2023]Flotufolastat F 18 (POSLUMA®) is an 18F-labelled radiohybrid (rh) prostate-specific membrane antigen (PSMA)-targeted imaging agent being developed by Blue Earth Diagnostics, a subsidiary of Bracco Imaging, for prostate cancer imaging. In May 2023, flotufolastat F 18 received its first approval in the USA as a radioactive diagnostic agent for positron emission tomography (PET) of PSMA positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. This article summarizes the milestones in the development of flotufolastat F 18 leading to this first approval.
Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis. [2023]Granulocyte monocyte adsorption (GMA) is considered one of the modalities for the remission induction of ulcerative colitis (UC). We previously reported that single-needle GMA (SN-GMA) could simplify the GMA. In the present study, the efficiency of SNGMA was examined according to the administration of corticosteroids (PSL) in UC patients. Blood sample were taken at proximal and distal side of the column during the SN-GMA treatment. Disease activity score (partial Mayo score: pMayo score) before and after the SN-GMA was investigated. The data of 18 patients with active UC (11 and 7 patients with PSL naïve and PSL use groups, respectively) treated with SN-GMA was analyzed. The mean pMayo score before the GMA treatment was comparable between the PSL naïve group (p = 0.26), whereas the score after the GMA treatment was significantly lower in PSL naïve group (0.8 + 0.6) than in PSL use group (3.0 + 2.1) (p = 0.04). Patients achieving the clinical remission were more observed in the PSL naive group (90.9%) than in the PSL use group (42.9%) (p = 0.047). The adsorption efficiency in the PSL naïve and PSL use groups were as follows: leukocytes (34.45 ± 7.43% vs 23.14 ± 7.56%: p = 0.008), granulocytes (41.74 ± 10.07% vs 27.99 ± 15.11%: p = 0.04), monocytes (32.59 ± 24.07% vs 33.16 ± 24.18%: p = 0.95), and lymphocytes (-1.87 ± 18.17% vs -3.79 ± 22.52%: p = 0.84), with a significant difference of the absorption efficiency in leukocytes and granulocytes. These data collectively indicate that the SN-GMA can be applied for the remission induction to active UC patients with a higher clinical remission rate in PSL naïve patients compared to PSL use patients.
Posaconazole: SCH 56592. [2019]Posaconazole [SCH 56592, SPRIAFIL, Noxafil] is an orally active triazole derivative that is in phase III trials with the Schering-Plough Research Institute (SPRI) in the US for the treatment of serious opportunistic fungal infections, including aspergillosis, candidiasis, coccidioidomycosis and fusariosis. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. Preclinical studies have also been conducted in Italy for the potential treatment of Cryptococcus neoformans infection (cryptococcosis).
Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections. [2018]Posaconazole (Noxafil(®)) is a triazole antifungal agent with an extended spectrum of antifungal activity. It is approved for the prophylaxis of invasive fungal infections in patients with neutropenia or in haematopoietic stem cell transplant recipients undergoing high-dose immunosuppressive therapy for graft-versus-host disease, and for the treatment of fungal infections. The efficacy and good tolerability of posaconazole oral suspension administered three or four times daily is well established. However, in order to overcome pharmacokinetic limitations associated with the suspension, a new gastro-resistant tablet and intravenous (IV) solution were developed. This article reviews the pharmacokinetic properties of the new posaconazole formulations and briefly summarizes efficacy data relating to the suspension. The pharmacokinetic advantages of the posaconazole gastro-resistant tablet compared with the suspension formulation include less interpatient variability, better systemic availability enabling once-daily administration, and absorption that is unaffected by changes in gastric pH or motility; in addition the tablets may be taken with or without food. The posaconazole tablet achieves higher and more consistent mean plasma concentrations than the suspension and, therefore, it is the preferred option to optimize efficacy in the prophylaxis or treatment of invasive fungal disease. The posaconazole IV solution provides an option for these same indications in patients who are unable to receive oral formulations.
Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution. [2015]Noxafil® (posaconazole; POS) is a potent, selective triazole antifungal approved for use in adults as an oral suspension, oral tablet and intravenous (IV) Solution. In support of pediatric administration of POS IV Solution to children
Breakthrough invasive fungal infection in an immunocompromised host while on posaconazole prophylaxis: an omission in patient counseling and follow-up. [2021]Posaconazole (Noxafil (Schering-Plough Corporation) is a triazole antifungal approved in the United States for the treatment of oropharyngeal candidiasis and for the prophylaxis of Candida and Aspergillus infections in the immunocompromised host. Posaconazole is available only as an oral suspension. When used for the prevention of Candida and Aspergillus infections, posaconazole should be taken three times daily with a high fat meal to maximize oral absorption. Failure to take posaconazole with food will lead to subtherapeutic serum levels and decreased clinical effectiveness of the drug.We report the case of a 49-year-old woman with acute myeloid leukemia who received 4 months of posaconazole as an outpatient for the labeled indication of prophylaxis of Candida and Aspergillus infections. During her last admission, the patient presented with an invasive sinus infection diagnosed as a mixed Aspergillus and Mucor etiology. The patient succumbed to this infection five weeks after presentation. Upon investigation it was found that the patient did not self-administer posaconazole as required in the product labeling, which may have led to drug failure in this patient. We submit this case to illustrate the importance of patient education regarding proper administration of posaconazole. The important role of the outpatient physician, nurse, and pharmacist in this setting is underscored.
In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. [2022]The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC(50) and MIC(90) values for posaconazole were 0.063 microg/ml and 1 mug/ml, respectively. MIC(90) values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 mug/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.
Treatment of the bone marrow failure in Fanconi anemia patients with danazol. [2013]More than 90% of Fanconi anemia (FA) patients experience progressive bone marrow failure during life with a median onset at 8 years of age. As matched sibling donor transplantation as preferred treatment is not available for the majority of patients, several synthetic androgens have been used as short-term treatment options for the marrow failure in FA patients for more than 50 years. Here, we retrospectively collected data on eight FA patients who received danazol for the off-label treatment of their marrow failure at a starting dose of approximately 5mg/kg body weight/die. The hematological parameters at the initiation of treatment were hemoglobin (Hb) 50% over the starting counts within 6 months and remained stable for up to 3 years despite careful reduction of the danazol dose per kg body weight. In 4 patients with a follow-up of 3 years, the platelets finally reached an average of 68,000/μL or 2.8 times over the starting values, while the Hb remained stable >11 g/dL. Danazol was reduced to 54% of the starting dose or 2.6 mg/kg/die. One FA-A patient with an unusually severe phenotype did not response with her PB counts to either danazol or oxymethalone within 6 months. None of the patients developed severe or unacceptable side-effects from the danazol treatment that led to the discontinuation of therapy. This initial description suggests that danazol might be an effective and well-tolerated treatment option for delaying the progressive marrow failure in FA patients for at least 3 years and longer.
[Effect of Compound Zaofan Pill on Bone Marrow MVD and VEGF of Patients with Chronic Aplastic Anemia]. [2018]To investigate the clinical efficacy of compound Zaofan pill combined with cyclosporine and androgen for treatment of patients with chronical aplastic anemia(CAA), and its effect on bone marrow microvessel density(MVD) and vascular endothelial growth factor(VEGF) of CAA patients.
A study to determine the effects of food and multiple dosing on the pharmacokinetics of vorinostat given orally to patients with advanced cancer. [2018]This phase I study, conducted in advanced-stage cancer patients, assessed the safety and tolerability of oral vorinostat (suberoylanilide hydroxamic acid), single-dose and multiple-dose pharmacokinetics of vorinostat, and the effect of a high-fat meal on vorinostat pharmacokinetics.
Danazol increases T regulatory cells in patients with aplastic anemia. [2018]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Danazol is an attenuated androgen and is used in the treatment of aplastic anemia (AA) in resource constraint settings. We chose to study the role of CD4+ CD25high CD127low FoxP3+ T regulatory cells (T-regs) in the pathophysiology of AA and their response to treatment with Danazol alone or in combination with immunosuppressive treatment (IST).
Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study. [2022]To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA).