Active clinical trials for "Mycoses"

Mycosis fungoides (MF) is an ultra-orphan disease of which the etiology remains unknown. MF is diagnosed by correlating clinical appearance with histopathological analysis of often multiple invasive skin punch biopsies. To move patient care and the development of novel treatments for MF forward, objective, sensitive and reliable tools that are preferably non-invasive are desired. Therefore, the objective of the current study is to phenotype the early stages of mycosis fungoides in detail and to assess the response of chlormethine (CL) gel monotherapy. With this approach the investigators aim to detect novel biomarkers and to establish methodologies for the (non-)invasive monitoring of MF.

Objectives of this clinical trial are to evaluate the safety, tolerability, pharmacokinetics and potential efficacy of the investigational drug, cobomarsen (MRG-106), in patients diagnosed with certain lymphomas and leukemias, including cutaneous T-cell lymphoma (CTCL) [mycosis fungoides (MF) subtype], chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) [activated B-cell (ABC) subtype], and adult T-cell leukemia/lymphoma (ATLL). Cobomarsen is an inhibitor of a molecule called miR-155 that is found at high levels in these types of cancers and may be important in promoting the growth and survival of the cancer cells. Participants in the clinical trial will receive weekly doses of cobomarsen administered by injection under the skin or into a vein, or by injection directly into cancerous lesions in the skin (for CTCL only). Blood samples will be collected to measure how cobomarsen is processed by the body, and other measurements will be performed to study how normal and cancerous cells of the immune system respond when exposed to cobomarsen.

The purpose of this pivotal study is to determine if intravenous Rezafungin is efficacious and safe in the treatment of candidemia and/or invasive candidiasis when compared to caspofungin (followed by optional oral fluconazole).

Invasive aspergillosis is a fungal infection which left untreated, is a significant cause of morbidity and mortality. Immunocompromised patient populations such as solid organ transplant and malignant hematology patients are especially susceptible to invasive fungal infections. Voriconazole is an anti-fungal agent that is frontline therapy for invasive aspergillosis. Treatment success is highly dependent on maintaining therapeutic voriconazole concentrations. The current published literature has established that treatment failure is associated with sub- and supra-therapeutic voriconazole concentrations. Maintaining therapeutic voriconazole concentrations however, is challenging due to the high inter and intra-patient variability in voriconazole pharmacokinetics. The complex kinetics of voriconazole renders current manufacturers' dosing guidelines ineffective. Much of this complexity has been linked to genetic polymorphisms in the cytochrome P450 2C19 gene, and it has been found that CYP2C19 genotype plays an important role in determining voriconazole exposure levels. Therapeutic drug monitoring has been found to increase efficacy of voriconazole treatment through the monitoring of patients' voriconazole levels, allowing for dosage adjustments in response to supra- or sub-therapeutic levels. There are few robust studies that have examined the effect of CYP2C19 genotype on voriconazole treatment outcomes. They have been unable to determine relationships between CYP2C19 genetic status, and clinical efficacy and safety. No studies to our knowledge have made dosing adjustments based on CYP2C19 genetic status. The study aim is to explore the utility of voriconazole dosing that is based on the genetic status of the patient in conjunction with therapeutic drug monitoring. Over the course of one year, solid organ transplant recipients at Toronto General Hospital and malignant hematology patients at Princess Margaret Cancer Centre receiving voriconazole therapy will be randomized into one of two trial arms: a control arm receiving therapeutic drug monitoring only, or a treatment arm receiving genotype-specific dosing in conjunction with therapeutic drug monitoring. The investigators will compare the proportion of patients that achieve voriconazole therapeutic concentrations, the number of dose adjustments needed to achieve therapeutic voriconazole levels, and clinical outcomes between trial arms.

This is a Phase 1, open-label study to evaluate the drug-drug interaction potential of a strong CYP3A4 inhibitor (itraconazole) and a pan-CYP inducer (rifampin) on APX001 in two parallel groups of healthy subjects.

This is a prospective, multi-center, randomized, open-label parallel arm study involving patients with proven or probable invasive endemic fungal infection to ascertain the pharmacokinetics, safety, efficacy, tolerability and health economics of oral SUBA-itraconazole compared to conventional itraconazole. Patients will receive randomized open-label study drug (SUBA-itraconazole or conventional itraconazole) over a 42 day period and then continue therapy until Day 180. Patients will be stratified based on clinically reported infection with the human immunodeficiency virus (HIV).

The pharmacokinetics of fluconazole are expected to be different in obese patients compared to non-obese patients. The investigators will determine fluconazole and free fluconazole concentrations in 16 obese patients and 8 healthy volunteers, who will receive oral and intravenous fluconazole in a semi-simultaneous design. A full pharmacokinetic curve will be obtained until 48 hours after intravenous administration.

Resminostat is a potent, orally available inhibitor of Class I, IIb and IV histone deacetylases (HDACs), including a pronounced activity against HDAC6. Resminostat targets epigenetic changes observed in tumour cells and has the potential to provide significant benefit to patients with advanced malignancies by inhibiting tumour progression and metastasis or even inducing tumour regression. This will be a Phase 1, open-label, non-randomized, single dose study of the absorption, metabolism, excretion of [14C] resminostat following a single oral dose in healthy male participants. The purpose of this study is to determine the absorption, metabolism, and excretion (AME) of [14C] resminostat and to characterize and determine the metabolites present in plasma, urine, and, where possible, faeces in healthy male participants following a single oral administration. Knowledge of the metabolism and excretion of parent drug and its metabolites is useful for evaluating the Metabolites in Safety Testing requirements elucidated in the International Conference on Harmonisation (ICH) M3, and the likelihood of effects of renal or hepatic impairment on the disposition of resminostat, and the likelihood for drug-drug interactions with resminostat. The results from this study may guide future study designs using special populations or evaluating the potential for drug-drug interactions.

The primary objective of this study is to assess and compare the safety of posaconazole with voriconazole in Japanese participants with aspergillosis.

The purpose of this study is to determine objective response rate (ORR), lasting at least 4 months (ORR4), with brentuximab vedotin in participants with cluster of differentiation antigen 30 positive (CD30+) cutaneous T-cell lymphoma [mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) ]compared to that achieved with therapy in the control arm.