A phase III, double blind, randomized study to evaluate safety and efficacy of BAL8557 versus voriconazole for primary treatment of invasive fungal disease caused by Apsergillus species or other filamentous fungi.
- Conditions
- Invasive fungal disease caused by Aspergillus species or other filamentous fungi.MedDRA version: 13.1Level: PTClassification code 10003488Term: AspergillosisSystem Organ Class: 10021881 - Infections and infestations
- Registration Number
- EUCTR2006-003868-59-BE
- Lead Sponsor
- Astellas Global Pharma Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 510
1. Patients and/or legally authorized representative(s), if applicable, who have been fully informed and who 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 = 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, having a negative urine or serum human chorionic gonadotropin (hCG) pregnancy test at the screening visit and be using 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 the purposes of this study.
5. Patients with proven, probable or possible IFD caused by Aspergillus species or other filamentous fungi as defined in the protocol.
Refer to the protocol for the criteria for Proven Invasive Fungal Disease, Probable Invasive Fungal Disease and Possible Invasive Fungal Disease.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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 interval >/= 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 or long QT syndrome);
The use of concomitant medications that prolong the QT/QTc interval.
5. Patients with evidence of persistent moderate to severe hepatic dysfunction at the time of randomization, defined as (may be rechecked using local laboratory:
• Total bilirubin = 3 times the upper limit of normal (ULN) or
• Alanine transaminase (ALT) or aspartate transaminase (AST) = 5 times ULN or
• Patients with known cirrohisis 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. John’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 Zygomycetes/ Mucormycosis or Scedosporium prolificans infection notexpected to respond to voriconazole treatment.
8. Patients with either 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 for any reason will be eligible
for enrollment.
11. Advanced human immunodeficiency virus infection with CD4 count < 200 or acquired immunodeficiency syndrome-defining condition, body weight < 40 kg.
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 isavuconazole.
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.
16. Patients who are unlikely to survive longer than 30 days or patients on mechanical ventilation.
17
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Primary Objective:<br>- To compare all cause mortality thourgh Day 42 following priamry treatment with isavuconazole versus voriconazole (VRC) in patients with IFD caused by Aspergillus species or other filamentous fungi;Secondary Objective: To compare the effects of treatment on:<br>- All cause mortality rate at Day 42 and Day 84<br>- Overall outcome at Day 42, end of treatment (EOT) and Day 84<br>- Overall outcome at Day 42, EOT and Day 84 in patients with mycologically confirmed<br>lower respiratory tract disease (LRTD)<br>- Overall outcome and mycological response at Day 42, EOT and Day 84 in the<br>subpopulations defined by the stratification variable<br>- Mycological response at Day 42, EOT and Day 84<br>• To characterize the safety and tolerance of treatment with ISA;Primary end point(s): All cause mortality through Day 42.
- Secondary Outcome Measures
Name Time Method