A Phase III, adjudicator-blinded, randomised study to evaluate the efficacy and safety of treatment with olorofim versus treatment with AmBisome® followed by standard of care (SOC) in patients with invasive fungal disease (IFD) caused by Aspergillus species

Phase 3

• Conditions: fungal infections on other places than skin or mucous membranes; invasive fungal infections due to Aspergillus species; 10017528

• Registration Number: NL-OMON56006
• Lead Sponsor: F2G Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

1. Male and female patients ages >= 18 years and weighing >= 30 kg, [*] or
Patients unable to write and/or read but who fully understand the oral
information given by the Investigator.
2. Patients with proven IA at any site or probable LRTD IA per
EORTC/MSG 2019 criteria as adapted for this study (see Appendix 2) and where
the duration of specific therapy for this episode of IA has been <= 28 days. For
purposes of this inclusion, the duration of specific therapy includes any
mould-active therapy given for this episode of IA whether subsequently judged
potentially effective or not.
3. Patients requiring therapy with an antifungal agent other than a
mould-active azole and who have had <= 96 hours of potentially effective prior
therapy. Potentially effective prior therapy includes any agent to which the
infecting strain of Aspergillus is likely to be susceptible. There are no
exclusions or limitations on such agents (eg, AmBisome® is permitted) other
than their duration.
Patients must meet at least one of these criteria:
a) Proven or suspected azole resistance in patients who have had <= 96 hours of
potentially effective prior therapy [*]
b) Breakthrough infection on triazole prophylaxis: patients who have had any
duration of prophylaxis prior to the breakthrough but <= 96 hours of potentially
effective prior therapy.
c) Any other medical reason an azole is inappropriate for the patient at
screening. In all cases, patients must have had <= 96 hours of potentially
effective prior therapy
(potential for drug-drug interaction, previous history of azole intolerance)
d) Invasive aspergillosis refractory to triazole therapy in patients who have
had <= 28 days of prior therapy where refractory IA was defined per an
international expert meeting report
4. AmBisome® is an appropriate therapy for the patient.
a) For avoidance of doubt, prior therapy with an amphotericin B (eg, AmBisome®
or other) is not an exclusion provided that such prior therapy does not exceed
the rules for maximum duration of potentially effective prior therapy discussed
as part of Inclusion Criterion 3.
5. Ability and willingness to comply with the protocol.
6. Female patients must be non-lactating and at no risk of pregnancy [*]
7. Male patients with female partners of childbearing potential must either
totally abstain from sexual intercourse or use a highly effective means of
contraception.
For more details, please refer to the protocol.

Exclusion Criteria

1. Women who are pregnant or breastfeeding.
2. Known history of allergy, hypersensitivity, or any serious reaction to any
component of the study drug (olorofim or AmBisome®).
3. Patients with only chronic aspergillosis, aspergilloma or allergic
bronchopulmonary aspergillosis.
4. Suspected mucormycosis (zygomycosis). Evidence for the presence of olorofim
non susceptible filamentous fungi such as Mucorales should be urgently followed
up. Increased vigilance for the possibility of mucormycosis (zygomycosis) is
required for suspected IA with negative baseline GM.
5. Patients with a known active second fungal infection of any type, other than
candidiasis being treated with fluconazole.
6. The requirement for ongoing use of echinocandin as Candida prophylaxis (for
avoidance of doubt, prior use of an echinocandin is permitted; if ongoing
prophylaxis for Candida is needed, then fluconazole must be an acceptable
choice [see Section 5.8.4.1, discussion of concomitant antifungal agents]).
7. Microbiological findings (eg, bacteriological, virological) or other
potential conditions that are temporally related and suggest a different
aetiology for the clinical features.
8. Patients with human immunodeficiency virus (HIV) infection who are currently
not receiving antiretroviral therapy. Patients with HIV infection receiving
antiretroviral therapy can participate in the study. In cases where HIV
infection is first diagnosed at the same time as the invasive fungal infection,
if antiretroviral therapy is commenced at the time of enrolment, then such
patients are eligible for enrolment.
9. Any known or suspected condition of the patient that may jeopardize
adherence to the protocol requirements or impede the accurate measurement of
efficacy (eg, neutropenia not expected to resolve, patients with uncontrolled
malignancy who are treatment refractory and receiving only palliative therapy).
10. 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 study with olorofim/F901318.
12. Treatment with any investigational drug in any clinical trial within the 30
days prior to the first administration of study drug except for unblinded
protocols (eg, open-label oncological regimen variations or biologic studies).
Prior to enrolling patients who are on other open label studies it is the
site's responsibility to ensure that the study criteria for that study allow
for enrolment into this study.
13. Patients receiving treatment limited to supportive care due to predicted
short survival time.
14. Patients with a baseline prolongation of Fridericia's Correction Formula
(QTcF) >= 500 msec, or at high risk for QT/QTc prolongation.
15. Evidence of hepatic dysfunction with any of the following abnormal
laboratory parameters at screening (for avoidance of doubt, liver transplant
recipients may be enrolled if their laboratory parameters do not meet the
exclusions):
a) Total bilirubin >= 2 × upper limit of the normal range (ULN)
b) Alanine transaminase or aspartate transaminase (AST) >= 3 × ULN
c) Patients with known cirrhosis or chronic hepatic failure (regardless of
ALT/AST/total bilirub
16. Prohibited concomitant medications: concomitant admi

Study & Design

• Study Type: Interventional
• Study Design: Not specified