An open-label single-arm Phase IIb study of F901318 as treatment of invasive fungal infections due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and other resistant fungi in patients lacking suitable alternative treatment options.

Phase 2

Completed

• Conditions: invasive fungal disease(IFD); invasive fungal infections; 10017528

• Registration Number: NL-OMON52686
• Lead Sponsor: F2G Biotech GmbH (FN 483749 x)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 12

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. 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:
i) Established use of oral, injected, transdermal, intravaginal or
implanted hormonal methods of contraception associated with inhibition
of ovulation
ii) Placement of an intrauterine device or intrauterine hormone-releasing
system
iii) Male sterilisation (with the appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate
iv) Bilateral tubal occlusion
v) Sexual abstinence (reliable sexual abstinence is acceptable but
periodic abstinence [e.g. calendar, ovulation, symptom-thermal, or post
ovulation methods] and withdrawal are not acceptable)., 4. 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., 5. 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, 6.
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, p

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 quality 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 enrollment (Section 5.9.1)., 15. Additional exclusion criteria required
by local regulatory or legal order.
- Prisoners or subjects who are legally institutionalized.
- Patients who are not suitable for participation, whatever the

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoint:<br /><br>• DRC-adjudicated overall response rate by pathogen at Day 42.</p><br>