E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Invasive fungal disease caused by Aspergillus species and Candida strains in patients with renal impairment as well as disease caused by rare moulds, yeats or dimorphic fungi. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10003486 |
E.1.2 | Term | Aspergillus infections |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049160 |
E.1.2 | Term | Candidaemia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To describe the safety and efficacy of isavuconazole in the treatment of invasive aspergillosis caused by Aspergillus fumigatus in patients with renal impairment or in patients with invasive fungal disease caused by rare moulds, yeasts or dimorphic fungi who require salvage therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to determine clinical and mycological response rate by pathogen group. Also the pharmacokinetic (PK) trough values of isavuconazole will be characterised
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
In selected sites with appropriate facilities and equipment the PK of BAL4815 and cleavage product BAL8728 will be evaluated in patients treated with isavuconazole. Seven plasma samples including samples from at least 10 patients aged < 42 years and 10 patients aged > 65 years will be collected on Day 7 or 14 for PK profiling. |
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E.3 | Principal inclusion criteria |
1.Patients who have been fully informed and who have given voluntary written informed consent or whose legally authorized representative(s), have been fully informed and have given voluntary written informed consent if applicable, 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 complty with the protocol. 3. Male and female patients aged 18 years or over. 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 Screening 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 who fall into one of the following 2 subgroups a)Patients with proven or probable invasive aspergillosis who have renal impairment, defined as serum creatinine clearance < 50 ml/min at enrollment or patients on dialysis, and who require primary therapy. NB: Patients fulfilling the criteria for “possible” invasive aspergillosis who also have renal impairment will be eligible for enrollment; if, however, it is not possible to confirm the invasive aspergillosis as “probable” or “proven” by culture, histology / cytology or galactomannan (GM) antigen within 7 days after the first administration of study medication, the patient will be withdrawn from the study. OR b) Patients with proven IFD caused by rare moulds, yeast, or dimorphic fungi (i.e. fungal pathogens other than Aspergillus fumigatus or Candida albicans) whether renally impaired or not who require salvage therapy for their IFD at the time of enrollment as defined below. Evidence of IFD based on respiratory samples may be acceptable after medical monitor’s approval. See body of protocol for definitions of proven, probable and possible invasive aspergillosis and primary and salvage therapy.
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E.4 | Principal exclusion criteria |
1. Pregnant/ breastfeeding women. 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. High risk patients for QT/QTc prolongation e.g -a family history of long QT syndrome, or, -other known pro-arrythimic conditions. 4. Evidence of severe hepatic dysfunction with any of the following laboratory parameters at Screening: - Total bilirubin 3 x upper limit of normal (ULN) - Alanine transaminase or aspartate transaminase 5 x ULN. 5. Concomitant use of astemizole, cisapride, rifampicin, rifabutin, ergot alkaloids, long acting barbiturates, cabamazepine, pimozide, quinidine, neostigmine or terfenadine in the 5 days prior to first administration of study medication. 6. Patients with chronic aspergillosis, aspergilloma, or ABPA. 7. Microbiological findings (e.g. virological) or other potential conditions that are temporally related and suggest a different etiology for the clinical features. 8. Advanced HIV infection with CD4 count <200 or acquired immunodeficiency syndrome-defining 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 (e.g. neutropenia not expected to resolve, patients with endocarditis, osteomyelitis, meningitis, uncontrolled malignancy (treatment refractory, palliative therapy only) with life expectancy of less than 30 days). 10. Patients with concomitant medical condition that, in the opinion of the investigator, may be an unacceptable additional risk to the patient should he/she particiopate in the study. 11. Patients previously enrolled in a phase III study with isavuconazole, (NB patients may be transferred from study WSA-CS-004 if mycology identifies zygomycetes which is not expected to be susceptible to vuconazole). 12. Treament with any investigational drug in any clinical trial 30 days prior to the first administration of study medication except for unblinded phase III trials. 13. Patients unlikely to survive longer than 5 days. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall outcome of treatment (clinical, mycological and radiological response) by sub group (e.g. type of pathogen) evaluated at Day 42 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 3 |