invasive fungal infections due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and other resistant fungi
Conditions
Interventions
Product Code: F901318
Pharmaceutical Form: Tablet
INN or Proposed INN: Applied for
Current Sponsor code: F901318
Other descriptive name: F901318
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
F2G Ltd.,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients aged at least 18 years 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, OR: Patients unable to write and / or read but who fully understand the oral information given by the Investigator (or nominated representative) 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 (hormonal implants, oral or injected hormonal contraceptives, intrauterine devices, two barrier methods such as a condom and a cervical cap) throughout the course of the study period. Reliable sexual abstinence is acceptable as a highly effective method of birth control for the purposes of this study. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception. 5. Male patients with female partners of childbearing potential must either abstain from sexual intercourse or use a reliable 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 IA-LRTD based on EORTC/MSG criteria (Appendix 2) but not meeting the criteria for culture proven invasive fungal infection. 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 pr
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. Evidence for the presence of F901318 non-susceptible filamentous fungi such as Mucorales should be urgently followed up and treatment should not be started or adapted. In particular, suspected IA with negative baseline GM should generally trigger increased vigilance. 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.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 endocarditis, 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). d) Use of concomitant medications that prolong the QT/QTc interval. 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.
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);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 with missing responses or considered not evaluable) 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 | — |
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, 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, EOT, Day 84 and 4-week FUwill be categorized as: o Success o Failure (where failure includes those patients with missing responses or considered not evaluable) • Clinical response overall and by DRC-adjudicated disease category at Day 7, Day 14, Day 28, Day 42, EOT, Day 84 and 4-week FU will be categorised as: o Success (Complete or Partial responseResolution of all or some clinical symptoms and physical findings associated with IFD) o Failure (Any other response than resolution of all or some clinical symptoms and physical findings associated with IFDNo response, missing response or considered not evaluable)• Where appropriate for the IFD, radiological response at Day 7, Day 14, Day 28, Day 42, 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. See Section 6.3 for further details on response definitions. • Mycological response at Day 7, Day 14, Day 28, Day 42, 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 persistent, 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 five DRC-adjudic | — |
Countries
Australia, Belgium, Germany, Netherlands, Spain
Contacts
Public ContactStart-up
IQVIA RDS Spain S.L.
Outcome results
None listed