A study to evaluate the efficacy and safety of olorofim versus AmBisome® for treatment of invasive aspergillosis.

Phase 1

• Conditions: invasive fungal infections due to Aspergillus spp.; MedDRA version: 20.0Level: PTClassification code 10017533Term: Fungal infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2021-000386-32-BE
• Lead Sponsor: F2G Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-08-23
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 225

Inclusion Criteria

1.Male and female patients ages = 18 years and weigh = 30kg, […] 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)Azole DDIs (or potential for DDIs) in patients who have had = 96 hours of potentially effective prior therapy.
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.
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 169
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

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.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 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 bilirubin).
16.Prohibited concomitant medications: concomitant administration of inhibitors of human DHODH (teriflunomide and leflunomide) are prohibited. There are currently no other absolutely prohibited concomitant medications or vaccines, but there are

Study & Design

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