invasive fungal infections due to Aspergillus spp. MedDRA version: 20.0 Level: PT Classification code 10017533 Term: Fungal infection System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
F2G Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male and female patients ages = 18 years and weigh more than 40kg, […] 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 […] 3.Patients requiring therapy with an antifungal agent other than a mould-active azole on the basis of IA refractory to mould-active azole therapy, proven resistance to the mould active azoles, breakthrough infection on mould-active triazole prophylaxis, or azole drug-drug interactions (or potential for drug-drug interactions). […] 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. 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. 8.Patients must be able to take oral medication. 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
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 use of an echinocandin as Candida prophylaxis (see 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.Human immunodeficiency virus (HIV) infection but not currently receiving antiretroviral therapy. 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: a)Total bilirubin = 2 × upper limit of the normal range (ULN) b)Alanine transaminase or aspartate transaminase = 3 × ULN c)Patients with known cirrhosis or chronic hepatic failure. 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 medications with potentially significant DDIs, and the management of potential interactions should be considered before study enrolment. 17.Additional exclusion criteria required by local regulatory authorities.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare all-cause mortality (ACM) at Day 42 following treatment with olorofim versus treatment with AmBisome® followed by standard of care (SOC) in the intent to treat (ITT) patients with Invasive Fungal Disease (IFD) caused by Aspergillus species (invasive aspergillosis [IA).;Secondary Objective: •To compare the treatment effects with olorofim versus AmBisome® followed by SOC on Data Review Committee-adjudicated assessment of overall outcome in patients with IA at Day 42, 84, and End Of Treatment. •To compare the treatment effects with olorofim versus treatment with AmBisome® followed by SOC on: -Investigator-assessed overall response at Day 14, 28, 42, 84, EOT, and Follow up (FU) -Galactomannan index at Day 14, 28, 42, 84, EOT, FU -All cause mortality at Day 84 -Survival time -Data Review Committee attribution of mortality to IA at Day 42 and 84 -Diagnosis of a secondary fungal infection at any time through EOT -Quality of life as measured by the 5 Level 5 Dimension (EQ-5D-5L) at Baseline, Days 14, 28, 42, 84, and EOT. •To assess the safety and tolerability of treatment with olorofim relative to AmBisome® followed by SOC up to Day 84 and FU visits. •To collect olorofim systemic exposure data for population pharmacokinetic modelling. •To collect health variables.;Primary end point(s): All cause mortality rate at Day 42 in the ITT population.;Timepoint(s) of evaluation of this end point: Day 42 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Data Review Committee-adjudicated assessment of overall response rate at EOT (key secondary analysis) and at Day 42 and Day 84. •Investigator assessment of clinical, radiological, and mycological response at Day 14, Day 28, Day 42, Day 84, End Of Treatment , and Follow up. •Galactomannan index on Day 14, Day 28, Day 42, Day 84, End Of Treatment, and Follow-Up. •All cause mortality rate at Day 84. •Survival time. •Data Review Committee attribution of mortality to IA at Day 42 and Day 84. •Diagnosis of a secondary fungal infection at any time through EOT. •Quality of life as judged by EQ-5D-5L at baseline, Day 14, Day 28, Day 42, Day 84, and EOT;Timepoint(s) of evaluation of this end point: -Day 14, Day 28, Day 42, Day 84, End Of Treatment and Follow-Up | — |
Countries
Australia, Belgium, Brazil, Canada, Egypt, France, Germany, Israel, Korea, Democratic People's Republic of, Malaysia, Netherlands, Poland, Singapore, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam
Contacts
Public ContactClinical Trial Operations
F2G Biotech GmbH
Outcome results
None listed