Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi

Acute invasive fungal infections caused by aspergillus, rare moulds, yeasts or dimorphic
fungi are life threatening diseases. Early treatment with highly effective anti-fungals
reduces mortality. This study investigates the safety and efficacy of isavuconazole in
participants with aspergillosis and renal impairment, and in participants suffering from
invasive infections from rare fungi.

Inclusion Criteria:

•Participants meeting EORTC/MSG (European Organization for the Research and Treatment of
Cancer/Mycoses Study Group) definition of proven or culture positive probable IFD (invasive
fungal disease) caused by rare moulds, yeasts, or dimorphic fungi (i.e. fungal pathogens
other than Aspergillus fumigatus or Candida species) whether renally impaired or not
(including dialysis) who require primary therapy for their IFD at the time of enrollment.

OR

•Participants who had proven or probable zygomycosis, whether renally impaired or not
(including dialysis), who require primary therapy. Zygomycosis must be documented by
culture or histology / cytology.

OR

•Participants meeting EORTC/MSG definition of proven or culture positive probable IFD
caused by rare moulds, yeasts, or dimorphic fungi (i.e., fungal pathogens other than
Aspergillus fumigatus or Candida species), whether RI or not (including dialysis), who were
refractory to current treatment defined as,

- Clear documentation of progression of disease. Note: radiological progression only in
association with white blood cell (WBC) count recovery was not acceptable.

- Failure to improve clinically despite receiving at least 7 days of standard antifungal
regimen. Prior to enrolling patients who fell into this category, the Medical Monitor
was contacted for approval.

OR

• Participants meeting EORTC/MSG definition of proven or culture positive probable IFD
caused by rare moulds, yeasts, or dimorphic fungi (i.e., fungal pathogens other than
Aspergillus fumigatus or Candida species), whether RI or not (including dialysis), who were
intolerant to current treatment for example:

- Doubling of serum creatinine value to higher than the upper limit of normal (ULN)
within 48 hours.

- Serum creatinine > 2.0 mg/mL and current treatment with polyene or IV voriconazole.

- 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
(hypertensive crisis, severe chills or shock).

- Documented inability to achieve adequate blood levels of posaconazole, voriconazole or
itraconazole.

Exclusion Criteria:

- A known condition of the participants that may jeopardize adherence to the protocol
requirements

- Participants who are unlikely to survive 30 days

- Participants with a body weight < 40 kg

- Women who are pregnant or breastfeeding