invasive fungal infections due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and other resistant fungi
Conditions
Sponsors
F2G Biotech GmbH (FN 483749 x)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male and female patients aged at least 18 years or male and female patients aged 16 years or 17 years and who weigh at least 40 kg 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 and in compliance with local regulations, OR: Patients unable to write and / or read but who fully understand the oral information given by the Investigator who have given oral informed consent witnessed in writing by an independent person and in compliance with local regulations. 2.Ability and willingness to comply with the protocol. 3.Patients must be able to take oral medication 4.Female patients must be non-lactating and at no risk of pregnancy for one of the following criteria: a.Postmenopausal for at least 1 year; b.Post-hysterectomy and/or post-bilateral ovariectomy; c.Of childbearing potential, with a negative urine or serum human chorionic gonadotropin pregnancy test at the Screening visit and must be using a highly effective method of birthcontrol throughout the course of the study period (further details cf protocol) 5.Male patients with female partners of childbearing potential must either totally abstain from sexual intercourse or use a highly effective means of contraception throughout study participation and agree to continue its use for 30 days after stopping study drug. 6.Patients with one of these 4 forms of invasive fungal infection confirmed by culture or other diagnostic (as agreed with the MM): a) Lomentospora (Scedosporium) prolificans (LoPro), b) Scedosporium spp., c) Aspergillus spp., d) Other F901318-susceptible fungi (as described in the IB or based on information provided by the MM, and in either case requiring approval of the MM), OR e) Probable LRTD IA based on EORTC/MSG criteria (Appendix 2) but not meeting the criteria for culture proven invasive fungal infection. *For further details on inclusion criterium 6, see the protocol footnote 7. Patients will also have limited alternative treatment options based on meeting one or more of the following criteria: a) Known or predicted resistance of the infecting isolate to all licensed agents. LoPro automatically meets this criterion – other fungi may qualify after discussion with the MM, b) Failure of available therapy. Failure to improve based on clinical or radiologic grounds despite receiving =7 days of standard antifungal treatment AND alternative licensed agents are either predicted to be ineffective or are contraindicated, c) Intolerance to available therapy. Current therapy cannot be continued due to therapy-related adverse reactions (e.g., increase in serum creatinine above upper limit of normal with an amphotericin, persistent visual disturbances with voriconazole, allergic reaction with any compound, or other recognized drug-related AE) AND alternative licensed agents are either predicted to be ineffective or are contraindicated, d) Inability to manage DDIs. Inability to continue current therapy due to DDIs that cannot be managed AND alternative licensed agents are either predicted to be ineffective or are contraindicated, e) Inability to produce therapeutic drug levels. Inability to produce or maintain therapeutic blood levels with current therapy AND alternative licensed agents are either predicted to be ineffective or are contraindicated f) An IV-only option (e.g., an amphotericin)
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. 3. Patients with chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis. 4. Suspected zygomycosis (mucormycosis) as the IFD used to qualify for the study. Evidence for the presence of F901318 non-susceptible filamentous fungi such as Mucorales should be urgently followed up. Increased vigilance for the possibility of zygomycosis is required for suspected IA with negative baseline GM. 5. Microbiological findings (e.g., virological) or other potential conditions that are temporally related and suggest a different etiology for the clinical features. 6. 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 enrollment, then such patients are eligible for enrollment. 7. 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 uncontrolled malignancy who are treatment refractory and receiving only palliative therapy). 8. 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. 9. Patients previously enrolled in a study with F901318. 10. 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 (e.g. open-label oncological regimen variations or biologic studies). Prior to enrolling patients that 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. 11. Patients receiving treatment limited to supportive care due to predicted short survival time. 12. Patients with a baseline prolongation of QTcF =500 msec, or at high risk for QT/QTc prolongation, e.g.a) A family history of long QT syndrome b) Other known pro-arrhythmic conditions c) Risk factors for Torsade de Pointes (e.g. uncompensated heart failure, abnormal plasma potassium or magnesium levels that cannot be corrected, an unstable cardiac condition during the last 30 days). 13. Evidence of hepatic dysfunction with any of the following abnormal laboratory parameters at Screening: a) Total bilirubin =2 x ULN b) Alanine transaminase or aspartate transaminase =3 x ULN c) Patients with known cirrhosis or chronic hepatic failure 14. Prohibited concomitant medications. Concomitant administration of inhibitors of human DHODH (teriflunomide and leflunomide) is prohibited. There are currently no other absolutely prohibited concomitant medications but there are medications with potentially significant DDIs and the management of potential interactions should be considered before study enrolment (Section 5.9.1). 15. Additional exclusion criteria required by local regulatory authorities. These include, but are not limited to,: • Patients accommodated in an institution because of regulatory or legal order. • Prisoners or subjects who are legally institutionalized. • Patients who are not suitable for participation, whatever the reason, as judged by the Investigator, including medic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Describe the Data Review Committee (DRC)-adjudicated efficacy of F901318 as treatment for infections due to resistant fungi in patients lacking suitable alternative treatment options.;Secondary Objective: • Describe the safety of F901318 as treatment for infections due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and other resistant fungi in patients lacking suitable alternative treatment options. • Describe the efficacy of F901318 in terms of Investigator-assessed overall response (integrating clinical, radiological and mycological response). • Describe all-cause mortality. • Characterize pharmacokinetics (PK) of study drug and metabolite(s) • Evaluate patient-reported outcomes based on the EQ-5D-5L questionnaire.;Primary end point(s): The primary efficacy endpoint is the DRC-adjudicated overall response at Day 42 as determined by an independent DRC using a combination of clinical, mycological and radiological results and will be presented overall and by each of the five DRC-adjudicated disease categories as: • Success • Failure (where failure includes those patients for whom data at Day42 cannot be collected or who are considered not evaluable at Day 42) The criteria for assessment and categorisation of the DRC-adjudicated overall response will be detailed in the DRC Charter and subsequently specified in the detailed SAP. Patients withdrawn from study drug due to an unsuccessful overall outcome are required per protocol to return for the EOT visit but will not be asked to return for the Day 42 and/or Day 84 visits; however, these patients will be considered as failures at all subsequent timepoints.;Timepoint(s) of evaluation of this end point: Day 42 main study phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • DRC-adjudicated overall response (overall and by DRC-adjudicated disease category) at Day 7, Day 14, Day 28 main study phase, EOT, Day 84 and 4-week FU* (as determined by an independent DRC using a combination of clinical, mycological and radiological results) categorised as: o Success o Failure • Investigator-assessed overall response (overall and by DRC-adjudicated disease category as determined by investigator using all available assessment results including clinical, mycological and radiologic results) at Day 7, Day 14, Day 28, Day 42 main study phase, EOT, Day 84 and 4-week FU* will be categorized as: o Success o Failure (where failure includes those patients with missing responses or considered not evaluable) • DRC-adjudicated and Investigator-assessed clinical response overall and by DRC-adjudicated disease category at Day 7, Day 14, Day 28, Day 42 main study phase, EOT, Day 84 and 4-week FU* will be categorised as: o Success (categories of Resolution-Complete and Resolution-Partial) o Failure (categories of Failure-Stable, Failure-Progression, and Results not available) • Where appropriate for the IFD, DRC-adjudicated and Investigatorassessed radiological response at Day 7, Day 14, Day 28, Day 42 main study phase, EOT, Day 84 and 4-week FU*. will be presented overall, by the 5 DRC-adjudicated disease categories and in addition by baseline susceptibility category. • DRC-adjudicated and Investigator-assessed mycological response at Day 7, Day 14, Day 28, Day 42 main study phase, EOT, Day 84 and 4-week FU*. will be presented overall, by the five DRC-adjudicated disease categories and in addition by baseline susceptibility category based on the categorised response of: o Success (Proven or presumed eradication) o Failure (Persistence, presumed persistence, Recurrent or emergent infection or any other response except proven or presumed eradication) • All-cause mortality rate will be summarised overall and by each of the fiv | — |
Countries
Argentina, Australia, Belgium, Brazil, Egypt, France, Germany, Israel, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Thailand, United Kingdom, United States
Contacts
Public ContactLesley Fitton, Clinical Operations
F2G Ltd.,
Outcome results
None listed