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.Estudio de fase III, doble ciego y aleatorizado para evaluar la seguridad y eficacia de BAL8557 frente a voriconazol en el tratamiento primario de enfermedades fúngicas invasivas, causadas por especies de Aspergillus u otros hongos filamentosos.

Phase 1

• Conditions: MedDRA version: 8.1Level: LLTClassification code 10003488Term: Aspergillosis; Invasive fungal disease caused by Aspergillus species or other filamentous fungi.Enfermedad fúngica invasiva causada por especies Aspergillus u otros hongos filamentosos

• Registration Number: EUCTR2006-003868-59-ES
• Lead Sponsor: Basilea Pharmaceutica Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-02-07
• Study Completion: 2013-03-28
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

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

Inclusion Criteria

1. Patients and/or legally authorized representative(s), if applicable, who have been fully informed and have given voluntary written informed consent
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 witnessed in writing by an independent person.

2. Ability and willingness to comply with the protocol.
3. Male and female patients aged = 18 years.
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 must have proven or probable IFD caused by Aspergillus species or other filamentous fungi as defined in the protocol.
Patients fulfilling the criteria for possible IFD as defined in the protocol will be eligible for enrollment; if, however, it is not possible to confirm IFD by culture, histology/ cytology or galactomannan (GM) antigen within the 7 days after the first administration of study medication will be withdrawn from the study.

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

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 a family history of long QT syndrome or other known pro-arrythmic conditions.
5.Evidence of moderate to severe hepatic or renal dysfunction with any of the following abnormal laboratory parameters at the screening visit:
-Total bilirubin ? 3 times the upper limit of normal (ULN)
-Alanine transaminase or aspartate transaminase ? 5 times ULN
-Calculated creatinine clearance < 50 mL/minutes
6.Concomitant use of astemizole, cisapride, rifampicin, rifabutin, ergot alkaloids, long acting barbiturates, carbamazepine, pimozide, quinidine, neostigmine or terfenadine, in the 5 days prior to first administration of study medication .
7.Inability to confirm proven / probable IFD by culture, histology/cytology or GM antigen detection for patients enrolled as possible IFD within the 7 days after the first administration of study medication, except for patients with lower respiratory tract infection who have had an allogenic bone marrow transplant or who have neutropenia.
8.Patients with any other invasive fungal infection other than Aspergillus species or other filamentous fungi and patients with Zygomycetes or Scedosporium prolificans infection not expected to respond to voriconazole treatment.
9.Patients with either chronic aspergillosis, aspergilloma, or ABPA.
10.Microbiological (e.g. virological) findings or other potential conditions that are temporally related and suggest an different etiology of the clinical features.
11.Patients who have received more than 4 cumulative days of systemic antifungal therapy other than fluconazole within the 7 days prior to the first administration of study medication.
12.Chronic granulomatous disease, severe combined immunodeficiency, advanced human immunodeficiency virus infection with CD4 count < 200 or acquired immunodeficiency syndrome defining condition, body weight < 40 kg.
13.Any known or suspected condition of the patient that may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy (e.g. neutropenia not expected to resolve, patients with endocarditis, osteomyelitis, meningitis, uncontrolled malignancy with life expectancy of less than 30 days).
14.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.
15.Patients previously enrolled in this study.
16.Treatment with any investigational drug in blinded phase III trials or any phase I and phase II trials within 30 days prior to the first administration of study medication.
17.Patients who are unlikely to survive longer than 5 days or patients on mechanical ventilation.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare overall outcome following primary treatment with BAL8557 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>Overall outcome at EOT and Day 84;<br>Response in patients with mycologically confirmed pulmonary disease;<br>Response in the subpopulations defined by the stratification variables;<br>Mycological response;<br>Survival rate. <br><br>To characterize the safety of treatment with BAL8557.<br><br>To characterize the pharmacokinetics (PK) of BAL4815 and cleavage product BAL8278.<br>;Primary end point(s): Overall outcome (clinical, mycological and radiological response) at Day 42.