A study to evaluate olorofim (F901318) for the treatment of invasive fungal infections in participants lacking suitable alternative treatment options.
An open label, single arm Phase IIb study of olorofim (F901318) in participants with invasive fungal infections with limited treatment options. Participants received study treatment for up to 12 weeks in the main phase of the study. At the Investigator's request and after discussion with the medical monitor, open-label treatment with F901318 could be continued in patients judged by the Investigator to need therapy beyond 84 days and considered likely to continue to benefit from extended treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
203
30mg oral tablets
Data Review Committee (DRC) Adjudicated Overall Response at Day 42
The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. For the primary statistical analysis of overall response rate, values were assigned to the DRC adjudicated overall response as follows: Success (Success-Complete, Success-Partial); Failure (Failure-Stable, Failure-Progression, Death, and participants for whom data at the Day 42 Study Visit could not be collected or participants who were considered not evaluable at the Day 42 Study Visit).
Time frame: Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for All Aspergillus
The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline. The Aspergillus- All category is a combination of participants with Aspergillus proven and Aspergillus probable (invasive aspergillosis lower respiratory tract disease) baseline disease category. Overall success is defined as a Complete or Partial Response.
Time frame: Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for Lomentospora Prolificans
The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent Data Review Committee using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline, this one is for participants with a proven infection due to Lomentospora prolificans. Success is defined as a Complete or Partial Response.
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Valley Fever Institute at Kern Medical Center
Bakersfield, California, United States
UC Davis Medical Center
Sacramento, California, United States
University of California San Diego Medical Center
San Diego, California, United States
Emory University
Atlanta, Georgia, United States
University of Chicago
Chicago, Illinois, United States
Johns Hopkins Hospital
Baltimore, Maryland, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Washington University School of Medicine
St Louis, Missouri, United States
Weill Cornell Medical College
New York, New York, United States
Stony Brook University Medical Center
Stony Brook, New York, United States
...and 72 more locations
Time frame: Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for for Scedosporium Species
The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline, this one is for participants with a proven infection due to Scedosporium species. Success is defined as a Complete or Partial Response.
Time frame: Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for Coccidioides Species
The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline, this one is for participants with proven infection due to Coccidioides species. Success is defined as a Complete or Partial Response.
Time frame: Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 42 for Other Olorofim Susceptible Fungi
The primary efficacy variable was the DRC-adjudicated overall response at the Day 42 Study Visit, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on EORTC/MSG criteria. This was also presented by each of the 5 major infections as adjudicated by the DRC at baseline, this one is for participants with proven infection due to other olorofim susceptible fungi. Success is defined as a Complete or Partial Response.
Time frame: Day 42 in the Main Phase of study treatment
DRC Adjudicated Overall Response at Day 84
DRC-adjudicated overall response at Day 84, as determined by an independent DRC using a combination of clinical, mycological, and radiological results based on the EORTC/MSG criteria. For the analysis of overall response rate, values were assigned to the DRC-adjudicated overall response as follows: Success (Success-Complete, Success-Partial); Failure (Failure-Stable, Failure-Progression, Death, and participants for whom data at the Study Visit could not be collected or participants who were considered not evaluable at the Study Visit).
Time frame: Day 84 in the Main Phase of study treatment
Investigator Assessed Overall Response at Day 42
Investigator-assessed overall response (as determined by the Investigator using all available assessment results including clinical, mycological and radiologic results based on the EORTC/MSG criteria) at Day 42, categorised by the same response criteria as in the primary endpoint: Success (Success-Complete, Success-Partial), Failure (Failure-Stable, Failure-Progression, Death, participants for whom data at Day 42 could not be collected or who were considered not evaluable at the specific visit).
Time frame: Day 42 in the Main Phase of study treatment
Investigator Assessed Overall Response at Day 84
Investigator-assessed overall response (as determined by the Investigator using all available assessment results including clinical, mycological and radiologic results based on the EORTC/MSG criteria) at Day 84, categorised by the same response criteria as in the primary endpoint: Success (Success-Complete, Success-Partial), Failure (Failure-Stable, Failure-Progression, Death, participants for whom data at Day 84 could not be collected or who were considered not evaluable at the specific visit).
Time frame: Day 84 in the Main Phase of study treatment
DRC Adjudicated Clinical Response at Day 42
DRC adjudicated clinical response at the Day 42 Study Visit, as determined by an independent Data Review Committee using clinical response results based on EORTC/MSG criteria. Resolution is defined as a Complete or Partial Response.
Time frame: Day 42 in the Main phase of study treatment
DRC Adjudicated Clinical Response at Day 84
DRC adjudicated clinical response at the Day 84 Study Visit, as determined by an independent DRC using clinical response results based on EORTC/MSG criteria. Resolution is defined as a Complete or Partial Response.
Time frame: Day 84 in the Main phase of study treatment
Investigator Assessed Clinical Response at Day 42
Investigator assessed clinical response at the Day 42 Study Visit using clinical response results based on the EORTC/MSG criteria. Resolution is defined as a Complete or Partial Response.
Time frame: Day 42 in the Main phase of study treatment
Investigator Assessed Clinical Response at Day 84
Investigator assessed clinical response at the Day 84 Study Visit using clinical response results based on the EORTC/MSG criteria. Resolution is defined as a Complete or Partial Response.
Time frame: Day 84 in the Main Phase of study treatment
DRC Adjudicated Mycological Response at Day 42
DRC adjudicated mycological response was assessed at the Day 42 Study Visit, as determined by an independent Data Review Committee using mycological response results based on EORTC/MSG criteria. Success is defined as eradication or presumed eradication.
Time frame: Day 42 in the Main Phase of study treatment
DRC Adjudicated Mycological Response at Day 84
DRC adjudicated mycological response was assessed at the Day 84 Study Visit, as determined by an independent DRC using mycological response results based on EORTC/MSG criteria. Success is defined as eradication or presumed eradication.
Time frame: Day 84 in the Main phase of study treatment
Investigator Assessed Mycological Response at Day 42
Mycological response was assessed by the Investigator at the Day 42 Study Visit using mycological response results based on EORTC/MSG criteria. Success is defined as eradication or presumed eradication.
Time frame: Day 42 in the Main Phase of study treatment
Investigator Assessed Mycological Response at Day 84
Mycological response was assessed by the Investigator at the Day 84 Study Visit using mycological response results based on EORTC/MSG criteria. Success is defined as eradication or presumed eradication.
Time frame: Day 84 in the Main Phase of study treatment
DRC Adjudicated Radiological Response at Day 42
In participants for whom radiology formed a part of their diagnosis, radiology evaluations were required on Day 42 and were adjudicated by an independent DRC. Radiological responses were assigned as per EORTC/MSG criteria.
Time frame: Day 42 in the Main phase of study treatment
DRC Adjudicated Radiological Response at Day 84
In participants for whom radiology formed a part of their diagnosis, radiology evaluations were required on Day 84 and were adjudicated by an independent DRC. Radiological responses were assigned as per EORTC/MSG criteria.
Time frame: Day 84 in the Main Phase of study treatment
Investigator Assessed Radiological Response at Day 42
In participants for whom radiology formed a part of their diagnosis, radiology evaluations were required on Day 42. Radiological responses were assessed by the Investigator using EORTC/MSG criteria.
Time frame: Day 42 in the Main Phase of study treatment
Investigator Assessed Radiological Response at Day 84
In participants for whom radiology formed a part of their diagnosis, radiology evaluations were required on Day 84. Radiological responses were assessed by the Investigator using EORTC/MSG criteria.
Time frame: Day 84 in the Main Phase of study treatment
All Cause Mortality Rate at Day 42
The all cause mortality rate at Day 42 uses the survival status that was entered at the study visit (which employs a window around each nominal study day).
Time frame: Day 42 in the Main Phase of study treatment
All Cause Mortality Rate at Day 84
The all cause mortality rate at Day 84 uses the survival status that was entered at the study visit (which employs a window around each nominal study day).
Time frame: Day 84 in the Main Phase of study treatment