Evaluate F901318 Treatment of Invasive Fungal Infections in Patients Lacking Treatment Options (FORMULA-OLS)

• ClinicalTrials.gov Identifier: NCT03583164
• Recruitment Status: Recruiting
• First Posted: July 11, 2018
• Last Update Posted: December 1, 2022
• Sponsor: F2G Biotech GmbH
• Collaborator: Iqvia Pty Ltd
• Information provided by (Responsible Party): F2G Biotech GmbH

Tracking Information

• First Submitted Date: May 17, 2018
• First Posted Date: July 11, 2018
• Last Update Posted Date: December 1, 2022
• Actual Study Start Date: June 6, 2018
• Actual Primary Completion Date: September 2, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2018)

DRC adjudicated overall response at Day 42 using a combination of clinical, mycological and radiological response [ Time Frame: Day 42 ]

DRC adjudicated overall response at Day 42 using a combination of clinical, mycological using a combination of clinical, mycological and radiological results

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 10, 2018)

• DRC adjudicated response at other time points, investigator assessed overall response, all cause mortality. [ Time Frame: Days 7, 14, 28, End Of Treatment (anytime during the study between first administration and Day 84), 84 and 4-week FU ]
  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.
• Clinical response [ Time Frame: 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 ]
  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
• Where appropriate for the IFD, radiological response [ Time Frame: 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 ]
  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).
• Mycological response by pathogen [ Time Frame: 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 ]
  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).
• Investigator-assessed overall response [ Time Frame: 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 ]
  (integration of clinical, radiological, and mycological response) see above.
• All-cause mortality [ Time Frame: Day 42, End Of Treatment (anytime during the study between first administration and Day 84), Day 84 and 4-week FU ]
  All-cause mortality will be assessed using survival status and, if applicable, death details will be recorded in the CRF

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluate F901318 Treatment of Invasive Fungal Infections in Patients Lacking Treatment Options
• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Invasive Fungal Infections

Intervention

Drug: F901318

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

Study Arms

Experimental: F901318

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.

Intervention: Drug: F901318

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 8, 2021): 200
• Original Estimated Enrollment (submitted: July 10, 2018): 100
• Estimated Study Completion Date: April 2023
• Actual Primary Completion Date: September 2, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Daniea Zinzi; 43 664 3582281; dzinzi@f2g.com

• Listed Location Countries: Australia, Belgium, Brazil, Egypt, France, Germany, Israel, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Thailand, Turkey, United Kingdom, United States, Vietnam

Administrative Information

• NCT Number: NCT03583164
• Other Study ID Numbers: F901318/0032
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: F2G Biotech GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: F2G Biotech GmbH
• Original Study Sponsor: Same as current
• Collaborators: Iqvia Pty Ltd

Investigators

• Principal Investigator: Sharon Chen; Westmead Hospital

• PRS Account: F2G Biotech GmbH
• Verification Date: November 2022