Evaluate F901318 (Olorofim) Treatment of Invasive Fungal Infections in Participants Lacking Treatment Options
- Registration Number
- NCT03583164
- Lead Sponsor
- F2G Biotech GmbH
- Brief Summary
A study to evaluate olorofim (F901318) for the treatment of invasive fungal infections in participants lacking suitable alternative treatment options.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 203
- 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
- Females 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
- Participants with invasive fungal disease
- Participants who have limited alternative treatment options
- Women who are pregnant or breastfeeding.
- Known history of allergy, hypersensitivity, or any serious reaction to any component of the study drug.
- Participants with chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis.
- Human Immunodeficiency Virus (HIV) infection but not currently receiving antiretroviral therapy.
- Participants with a medical condition that may jeopardize adherence to the protocol or may cause unacceptable additional risk to the participant
- Previously enrolled participants or participants enrolled in any clinical trial within the last 30 days
- Participants receiving treatment limited to supportive care due to predicted short survival time.
- Prohibited concomitant medications.
- Any exclusion criteria required by local regulatory authorities.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Olorofim (F901318) Olorofim Olorofim (F901318) was given orally for up to 90 days in the Main Study Phase and could be continued for those participants entering the Extended Treatment Phase. Patients received fixed doses comprising of a 1-day loading dose of 150 mg of olorofim twice a day followed by a maintenance dose of 90 mg of olorofim twice a day. Up until Protocol Amendment 06, 58 patients received a weight-based olorofim dosing consisting of a 1-day loading dose of 4 mg/kg/day on Day 1, then a maintenance dose of 2.5 mg/kg/day (divided into 2 or 3 doses). The dose was then adjusted based on plasma levels of olorofim with the maximum total daily dose of 300 mg.
- Primary Outcome Measures
Name Time Method Data Review Committee (DRC) Adjudicated Overall Response at Day 42 Day 42 in the Main Phase of study treatment 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).
- Secondary Outcome Measures
Name Time Method DRC Adjudicated Overall Response at Day 42 for for Scedosporium Species Day 42 in the Main Phase of study treatment 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.
Investigator Assessed Overall Response at Day 84 Day 84 in the Main Phase of study treatment 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).
DRC Adjudicated Overall Response at Day 42 for All Aspergillus Day 42 in the Main Phase of study treatment 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.
Investigator Assessed Overall Response at Day 42 Day 42 in the Main Phase of study treatment 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).
Investigator Assessed Clinical Response at Day 84 Day 84 in the Main Phase of study treatment 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.
All Cause Mortality Rate at Day 42 Day 42 in the Main Phase of study treatment 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).
DRC Adjudicated Overall Response at Day 42 for Other Olorofim Susceptible Fungi Day 42 in the Main Phase of study treatment 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.
DRC Adjudicated Overall Response at Day 84 Day 84 in the Main Phase of study treatment 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).
DRC Adjudicated Mycological Response at Day 42 Day 42 in the Main Phase of study treatment 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.
DRC Adjudicated Mycological Response at Day 84 Day 84 in the Main phase of study treatment 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.
DRC Adjudicated Radiological Response at Day 84 Day 84 in the Main Phase of study treatment 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.
Investigator Assessed Radiological Response at Day 42 Day 42 in the Main Phase of study treatment 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.
DRC Adjudicated Overall Response at Day 42 for Lomentospora Prolificans 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 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.
DRC Adjudicated Overall Response at Day 42 for Coccidioides Species Day 42 in the Main Phase of study treatment 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.
Investigator Assessed Mycological Response at Day 42 Day 42 in the Main Phase of study treatment 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.
Investigator Assessed Mycological Response at Day 84 Day 84 in the Main Phase of study treatment 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.
DRC Adjudicated Radiological Response at Day 42 Day 42 in the Main phase of study treatment 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.
DRC Adjudicated Clinical Response at Day 42 Day 42 in the Main phase of study treatment 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.
DRC Adjudicated Clinical Response at Day 84 Day 84 in the Main phase of study treatment 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.
Investigator Assessed Clinical Response at Day 42 Day 42 in the Main phase of study treatment 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.
All Cause Mortality Rate at Day 84 Day 84 in the Main Phase of study treatment 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).
Investigator Assessed Radiological Response at Day 84 Day 84 in the Main Phase of study treatment 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.
Trial Locations
- Locations (82)
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
🇺🇸Saint 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
Scroll for more (72 remaining)Valley Fever Institute at Kern Medical Center🇺🇸Bakersfield, California, United States