Evaluate F901318 Treatment of Invasive Fungal Infections in Patients Lacking Treatment Options

Study Overview
=================
Brief Summary
-----------------
A study to evaluate F901318 (study drug) for the treatment of invasive fungal infections in patients lacking suitable alternative treatment options.

Detailed Description
-----------------
This is the first study in patients of F901318. Patients with a limited treatment options will be enrolled and treated with F901318 (olorofim) for up to 12 weeks.

Official Title
-----------------
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

Conditions
-----------------
Invasive Fungal Infections

Intervention / Treatment
-----------------
* Drug: F901318


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female aged at least 18 years, or male and female aged 16 years or 17 years and who weigh at least 40 kg whom have given informed consent Ability and willingness to comply with the protocol. Able to take oral medication Female must be non-lactating and at no risk of pregnancy Male with female partners of childbearing potential must either abstain from sexual intercourse or use a highly effective means of contraception Patients with invasive fungal disease Patients who have limited alternative treatment options Exclusion Criteria: Women who are pregnant or breastfeeding. Known history of allergy, hypersensitivity, or any serious reaction to any component of the study drug. Patients with chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis. HIV infection but not currently receiving antiretroviral therapy. Patients with a medical condition that may jeopardize adherence to the protocol or may cause unacceptable additional risk to the patient Previously enrolled patients or patients enrolled in any clinical trial within the last 30 days Patients receiving treatment limited to supportive care due to predicted short survival time. Prohibited concomitant medications. Any exclusion criteria required by local regulatory authorities.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: F901318<br>open-label single-arm of F901318 as treatment of invasive fungal infections due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and other resistant fungi which are susceptible to F901318 in patients with limited treatment options. | Drug: F901318<br>* 30mg tablets with a maximum daily dose of 300mg with dose adjustments according to plasma levels of F901318 and concomitant treatment with CYP inducers or inhibitors<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DRC adjudicated overall response at Day 42 using a combination of clinical, mycological and radiological response | DRC adjudicated overall response at Day 42 using a combination of clinical, mycological using a combination of clinical, mycological and radiological results | Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Where appropriate for the IFD, radiological response | As relevant for the IFD under study, baseline radiological assessments of IFD will be performed at screening and during the course of the study in accordance with local practice and as clinically indicated. A ≥ 90% improvement. A ≥ 50 to < 90% improvement. A ≥ 25% to < 50% improvement. No Change to < 25% improvement. Worsening in aggregate (across all lesions if more than one lesion). No signs on radiological images at screening. Results not available (i.e. assessment not performed at scheduled time-point). | Day 7, Day 14, Day 28, Day 42, End Of Treatment (anytime during the study between first administration and Day 84), Day 84 and 4-week FU | 
| Mycological response by pathogen | Assessment of mycological response as follows: Eradication of original causative organism cultured or identified by histology/cytology at baseline and no emergence of new causative organisms. Presumed eradication - missing documentation of eradication of causative organism and no evidence of new causative organisms + resolution of all or some clinical symptoms and physical findings of IFD. Persistence of the original causative organism cultured or identified by histology/cytology at baseline or emergence of a new causative organism. Presumed persistence - missing documentation of persistence of causative organism and no documentation of emergence of new causative organisms + either (i) no resolution or (ii) worsening of any clinical symptoms and physical findings of IFD. No mycological Follow-up results available (no diagnostic test done at the scheduled time-point). No mycological evidence at baseline (negative diagnostic test(s) or not done). | Day 7, Day 14, Day 28, Day 42, End Of Treatment (anytime during the study between first administration and Day 84), Day 84 and 4-week FU | 
| Investigator-assessed overall response | (integration of clinical, radiological, and mycological response) see above. | Day 7, Day 14, Day 28, Day 42, End Of Treatment (anytime during the study between first administration and Day 84), Day 84 and 4-week FU | 
| All-cause mortality | All-cause mortality will be assessed using survival status and, if applicable, death details will be recorded in the CRF | Day 42, End Of Treatment (anytime during the study between first administration and Day 84), Day 84 and 4-week FU | 
| DRC adjudicated response at other time points, investigator assessed overall response, all cause mortality. | Assessment of overall response will be based on all available assessments (clinical, radiological and mycological). See response assessments listed below. Treatment success is defined as complete or partial. Treatment failure is defined as stable response or progression of IFD. The criteria for assessment of overall response are summarised below: Success -complete, Success -partial, Failure -stable, Failure -progression. | Days 7, 14, 28, End Of Treatment (anytime during the study between first administration and Day 84), 84 and 4-week FU | 
| Clinical response | The Investigator will identify and assess clinical signs and symptoms related to the IFD reported for each patient. Response assessment will be based on changes from baseline signs and symptoms | Day 7, Day 14, Day 28, Day 42, End Of Treatment (anytime during the study between first administration and Day 84), Day 84 and 4-week FU | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anti fungal, Invasive aspergillosis, Rare moulds