Health Condition 1: B449- Aspergillosis, unspecified Health Condition 2: null- Invasive fungal disease (IFD) caused by Aspergillus species or other filamentous fungi
Conditions
Interventions
Intervention1: Isavuconazole: Isavuconazole (BAL4815) is administered as a water soluble pro-drug Isavuconazonium
sulphate (BAL8557). Throughout the protocol all doses of the pro-drug are expressed as
Sponsors
Astellas Pharma Global Development Inc APGD
Quintiles Research India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients and/or legally authorized representative(s), if applicable, who have been fully informed and have given voluntary written informed consent and HIPAA Authorization for U.S. sites, or equivalent privacy language as per national regulations OR patients unable to write and/or read but who fully understand the oral information given by the investigator (or nominated representative), and who have given oral informed consent, and HIPAA Authorization for U.S. sites, or equivalent privacy language as per national regulations, witnessed in writing by an independent person. 2. Ability and willingness to comply with the protocol. 3. Male and female patients aged ï?³ 18 years, at time of signing the informed consent form. 4. Female patients must be non-lactating and at no risk for pregnancy for one of the following reasons: • Postmenopausal for at least 1 year • Post hysterectomy and/or post bilateral ovariectomy • If of childbearing potential, patient must have a negative urine or serum human chorionic gonadotropin (hCG) pregnancy test at the Screening visit and must use a highly effective method of birth control throughout the course of the study. Reliable sexual abstinence throughout the course of the study is acceptable as a highly effective method of birth control for purposes of this study. 5. Patients with proven, probable or possible IFD caused by Aspergillus species or other filamentous fungi as defined below: NB: Patients fulfilling the criteria for â??possibleâ?? IFD will be eligible for enrollment; however, diagnostic tests to confirm the IFD as â??probableâ?? or â??provenâ?? by culture and histology/cytology or galactomannan (GM) antigen (Aspergillus only) must be completed within 7 days after the first administration of study medication. Proven Invasive Fungal Disease Patients with a positive diagnostic test obtained prior to first dose and up to 7 days after the first administration of study medication: (for definitions, see Section 4.2) - Either histopathologic, cytopathologic, or wet mount examination of a needle aspiration or biopsy specimen showing hyphal forms with evidence of associated tissue damage (either microscopically or as an infiltrate or lesion by imaging) OR - Recovery of a mold from a sample for culture obtained by a sterile procedure from a normally sterile and clinically or radiologically abnormal site consistent with an infectious disease process (e.g. transbronchial biopsy, open-lung biopsy, or brain biopsy). OR - Blood culture that yields a mold (e.g. Fusarium species) in the context of a compatible infectious disease process. In an immunocompetent host, a blood culture that yields Aspergillus species is to be considered a contaminant and the patient is not eligible for enrollment. Host factors (a) and clinical features (b) are not required for patients with proven IFD. However, if such host factors and clinical features are present at baseline, they will be recorded in the eCRF. Probable Invasive Fungal Disease At least one host factor [a] as below PLUS At least one clinical feature [b] as below PLUS At least one mycological criterion [c] as below a. HOST FACTORS: • Either recently resolved or ongoing neutropenia (neutropenia defined as absolute neutrophil count < 0.5 x 109/L [ < 500/mm3] for ï?
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant or breastfeeding. 2. Known history of allergy, hypersensitivity to, or any serious reaction to the azole class of antifungals or to any component of the study medication. 3. Patients for whom VRC is contra-indicated, including cardiovascular findings. 4. Patients at high risk for QT/QTc prolongation such as: • Baseline prolongation of QTcF ï?³ 500 msec; • Risk factors for Torsade de Pointes (e.g. uncompensated heart failure, abnormal potassium or magnesium levels that cannot be corrected, any unstable cardiac condition during the last 30 days, or a family history of long QT syndrome); • The use of concomitant medications that prolong the QT/QTc interval. 5. Patients with evidence of hepatic dysfunction at the time of randomization, defined as (may be re-checked using local laboratory): • Total bilirubin ï?³ 3 times the upper limit of normal (ULN) or • Alanine transaminase (ALT) or aspartate transaminase (AST) ï?³ 5 times ULN or • Patients with known cirrhosis or chronic hepatic failure. 6. Concomitant use of sirolimus, efavirenz, ritonavir, astemizole, cisapride, rifampin/rifampicin, rifabutin, ergot alkaloids, long acting barbiturates, carbamazepine, pimozide, quinidine, neostigmine, terfenadine, ketoconazole, valproic acid, or St. Johnâ??s Wort in the 5 days prior to first administration of study medication. 7. Patients with any other invasive fungal infection other than Aspergillus species or other filamentous fungi and patients with Zygomycosis/Mucormycosis or Scedosporium prolificans infection not expected to respond to voriconazole treatment. 8. Patients with chronic aspergillosis, aspergilloma or Allergic Bronchopulmonary Aspergillosis (ABPA). 9. Microbiological (e.g. virological) findings or other potential conditions that are temporally related and suggest a different etiology of the clinical features in the absence of evidence of systemic aspergillosis infection. 10. Patients who have been administered more than 4 cumulative days of itraconazole, voriconazole, or posaconazole, for any reason, within the 7 days prior to the first administration of study medication. • Patients with applicable host factors who develop new evidence of IFD while on prophylactic therapy, for at least 14 days, with either an amphotericin B product or an echinocandin, will be eligible for enrollment. • Prior use of fluconazole of any duration and any reason will be eligible for enrollment. 11. Advanced human immunodeficiency virus infection with CD4 count 200 or acquired immunodeficiency syndrome defining condition. 12. Any known or suspected condition of the patient that may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy, for example, neutropenia not expected to resolve, patients with fungal endocarditis, fungal osteomyelitis, fungal meningitis, palliative therapy only for underlying condition. 13. Patients with a concomitant medical condition that, in the opinion of the investigator, may be an unacceptable additional risk to the patient should he/she participate in the study. 14. Patients previously enrolled in a Phase III study with ISA. 15. Treatment with any investigational drug in any clinical trial within 30 days prior to the first administration of study medication except open label protocols. <br
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| All-cause mortality through Day 42Timepoint: All-cause mortality through Day 42 | — |
Secondary
| Measure | Time frame |
|---|---|
| â?¢Allâ??cause mortality rate at â?¢Overall outcome of treatment (based on Data Review Committeeâ??s assessment of clinical, radiological and mycological response) â?¢Overall outcome of treatment (based on Investigatorâ??s assessment of clinical, radiological and mycological response) patients â?¢Clinical response â?¢Mycological response â?¢Radiological response Timepoint: â?¢Day 84 â?¢Day 42, EOT and Day 84 â?¢Day 42, EOT and Day 84 â?¢Day 42, EOT and Day 84 â?¢Day 42, EOT and Day 84 â?¢Day 42, EOT and Day 84 | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Egypt, France, Germany, India, Italy, Lebanon, Mexico, Poland, Russian Federation, South Africa, Thailand, United States of America
Contacts
Public ContactSuchela Srivatsa
Quintiles Research (India) Private Limited
Outcome results
None listed