Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi

• Conditions: Invasive fungal disease caused by Aspergillus species in patients with renal impairment as well as disease caused by rare moulds, yeasts or dimorphic fungi.; MedDRA version: 14.1Level: HLTClassification code 10003486Term: Aspergillus infectionsSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2006-005003-33-DE
• Lead Sponsor: Astellas Global Pharma Development, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-22
• Last Update Posted: 14 April 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

1. Patients and/or legal authorized representative(s), if applicable, who have been fully informed and have given voluntary written informed consent and HIPAA Authorization for US 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) who have given oral informed consent, and HIPAA Authorization for US 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 the time of signing the informed consent form.
4. Female patients must be non-lactating and at no risk for pregnancy
5. Patients who fall into one of the following 5 subgroups:
a) Patients with proven, probable or possible invasive aspergillosis who have renal impairment ( including dialysis) OR
b) Patients meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare molds, yeasts, or dimorphic fungi, whether renally impaired or not (including dialysis), who require primary therapy for their IFD at the time of enrollment as defined in the body of the protocol.
OR
c) Patients who have proven or probable zygomycosis, whether they are renally impaired or not (including dialysis), who require primary therapy. Zygomycosis must be documented by culture or histology /cytology.
OR
d) Patients meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare molds, yeasts, or dimorphic fungi, whether renally impaired or not (including dialysis), who are refractory to current treatment defined as:
-clear documentation of progression of disease
-failure to improve clinically despite currently receiving at least 7 days of standard antifungal regimen
OR
e) Patients meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare molds, yeasts, or dimorphic fungi, whether renally impaired or not (including dialysis), who are intolerant to current treatment, for example:
-doubling of serum creatinine value to higher than the upper limit of normal (ULN) within 48 hours or
-serum creatinine > 2.0 mg/ml and current treatment with polyene or IV voriconazole
or
-other significant drug-related adverse reaction(s) to the current
antifungal agent, resulting in discontinuation of the treatment, e.g.
persistence of visual disturbance, allergic reaction, phototoxicity or
severe infusion reaction
or
-documented inability to achieve adequate blood levels of posaconazole, voriconazole or itraconazole.

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 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

1. Women who are pregnant or breastfeeding.
2. Known history of allergy, hypersensitivity, or any serious reaction to the azole class of antifungals or to any component of the study medication.
3. Patients at high risk for QT prolongation
4. Patients with evidence of hepatic dysfunction with any of the
following abnormalities at the time of enrollment:
? Total bilirubin > 3 x upper limit of normal (ULN) OR
? Alanine transaminase (ALT) or aspartate transaminase (AST) > 5 x ULN OR
? Patients with known cirrhosis or chronic hepatic failure
5. Concomitant use of astemizole, cisapride, rifampin/rifampicin,
rifabutin, ergot alkaloids, long acting barbiturates, ritonavir, efavirenz, carbamazepine, pimozide, quinidine, neostigmine,
terfenadine, ketoconazole, valproic acid or St. John's Wort in the 5 days prior to first administration of study medication.
6. Patients with either chronic aspergillosis, aspergilloma or allergic
bronchopulmonary aspergillosis (ABPA).
7. Microbiological findings (e.g. virological) or other potential conditions that are temporally related and suggest a different etiology for the clinical features in the absence of evidence of
systemic fungal infection.
8. Advanced human immunodeficiency virus (HIV) infection with CD4 count < 50 or uncontrolled acquired immunodeficiency syndromedefining condition.
9. Any known or suspected condition of the patient that may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy
10. 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.
11. Patients previously enrolled in a phase III study with ISA.
12. Treatment with any investigational drug in any clinical trial 30 days prior to the first administration of study medication except open label protocols.
13. Patients who are unlikely to survive 30 days.
14. Patients with a body weight < 40 kg.
15. Patients who need primary therapy for invasive aspergillosis 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified