Invasive Fungal Infections
Conditions
Keywords
Anti fungal, Invasive aspergillosis, Rare moulds, Coccidioidomycosis
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.
Interventions
DRUGOlorofim
30mg oral tablets
Sponsors
Iqvia Pty Ltd
F2G Biotech GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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 * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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). |
| 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 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 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. |
| 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. |
| 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. |
| 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 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. |
| 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. |
| 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). |
| 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 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. |
Countries
Australia, Belgium, Brazil, Egypt, France, Germany, Israel, Netherlands, Poland, Russia, South Korea, Spain, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Participant flow
Recruitment details
This study planned to enrol approximately 200 patients at approximately 100 centres globally over at least 60 months. The first patient was enrolled into the study on 06 June 2018 and the Last subject last visit date was 10 February 2023 (for the Extended Treatment Phase).
Participants by arm
| Arm | Count |
|---|---|
| Olorofim (F901318) Open-label single-arm of Olorofim (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.
Olorofim 30 mg tablets were given for up to 90 days in the Main Study Phase and could be continued for those 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. | 203 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Clinically significant lab value in Extended Phase | 4 |
| Overall Study | Clinically significant lab value in Main Phase | 2 |
| Overall Study | Death in Extended Phase | 13 |
| Overall Study | Death in Main Phase | 35 |
| Overall Study | Intolerable adverse event in Extended Phase | 1 |
| Overall Study | Intolerable adverse event in Main Phase | 3 |
| Overall Study | Lack of compliance in Extended Phase | 2 |
| Overall Study | Lost to follow up in Extended Phase | 3 |
| Overall Study | Lost to Follow up in Main Phase | 1 |
| Overall Study | Other not specified reason in Main Phase | 2 |
| Overall Study | Physician decision in Extended Phase | 2 |
| Overall Study | Physician decision in Main Phase | 1 |
| Overall Study | Treatment failure in Extended Phase | 4 |
| Overall Study | Treatment failure in Main Phase | 2 |
| Overall Study | Withdrawal of consent in Extended Phase | 2 |
Baseline characteristics
| Characteristic | Olorofim (F901318) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 52 Participants |
| Age, Categorical Between 18 and 65 years | 151 Participants |
| Age, Continuous | 56.57 years |
| Baseline Data Review Committee-Adjudicated Disease Category Aspergillus - All | 101 Participants |
| Baseline Data Review Committee-Adjudicated Disease Category Coccidioides | 41 Participants |
| Baseline Data Review Committee-Adjudicated Disease Category Lomentospora (Scedosporium) prolificans | 26 Participants |
| Baseline Data Review Committee-Adjudicated Disease Category No DRC adjudicated baseline fungus | 1 Participants |
| Baseline Data Review Committee-Adjudicated Disease Category Other Olorofim-susceptible fungi | 12 Participants |
| Baseline Data Review Committee-Adjudicated Disease Category Scedosporium spp. | 22 Participants |
| Body Mass Index | 22.954 kg/m^2 |
| Duration from Baseline Fungal Infection Start to First Treatment Administration | 75.0 Days |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race (NIH/OMB) White | 160 Participants |
| Reason for Limited Treatment Options Failure of available therapy | 110 Participants |
| Reason for Limited Treatment Options Inability to manage drug interactions | 7 Participants |
| Reason for Limited Treatment Options Inability to produce therapeutic drug levels | 2 Participants |
| Reason for Limited Treatment Options Intolerance to available therapy | 29 Participants |
| Reason for Limited Treatment Options IV only option produced clinical response and standard to switch to oral azole | 10 Participants |
| Reason for Limited Treatment Options Known/predicted resistance to all licensed agents | 42 Participants |
| Reason for Limited Treatment Options Missing | 1 Participants |
| Reason for Limited Treatment Options Other, received Medical Monitor approval | 2 Participants |
| Region of Enrollment Australia | 18 participants |
| Region of Enrollment Belgium | 45 participants |
| Region of Enrollment Egypt | 1 participants |
| Region of Enrollment Germany | 5 participants |
| Region of Enrollment Israel | 8 participants |
| Region of Enrollment Netherlands | 16 participants |
| Region of Enrollment Russia | 3 participants |
| Region of Enrollment Spain | 6 participants |
| Region of Enrollment Thailand | 2 participants |
| Region of Enrollment United Kingdom | 3 participants |
| Region of Enrollment United States | 96 participants |
| Sex: Female, Male Female | 79 Participants |
| Sex: Female, Male Male | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 50 / 203 |
| other Total, other adverse events | 186 / 203 |
| serious Total, serious adverse events | 132 / 203 |
Outcome results
Primary
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
Population: The modified Intent to Treat (mITT) analysis set contains all participants in the ITT set who were assigned to a DRC-adjudicated disease category. The mITT population and subpopulations based on the DRC-adjudicated disease categories were used for the analysis of efficacy data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | Data Review Committee (DRC) Adjudicated Overall Response at Day 42 | 28.7 Response rate percentage |
Secondary
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
Population: The mITT set contains all patients in the Intent to Treat analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | All Cause Mortality Rate at Day 42 | 11.9 Mortality rate percentage |
Secondary
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
Population: The mITT set contains all patients in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | All Cause Mortality Rate at Day 84 | 16.3 Mortality rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Clinical Response at Day 42 | 59.9 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Clinical Response at Day 84 | 54.0 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Mycological Response at Day 42 | 18.3 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Mycological Response at Day 84 | 22.5 Response rate percentage |
Secondary
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
Population: The mITT subpopulation contains all participants in the ITT set who had a DRC-adjudicated baseline infection of All Aspergillus.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Overall Response at Day 42 for All Aspergillus | 34.7 Response rate percentage |
Secondary
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
Population: The mITT subpopulation contains all participants in the ITT set who had a DRC-adjudicated baseline infection due to Coccidioides species.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Overall Response at Day 42 for Coccidioides Species | 0.0 Response rate percentage |
Secondary
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
Population: The mITT subpopulation contains all participants in the ITT set who had a DRC-adjudicated baseline infection due to Scedosporium species.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Overall Response at Day 42 for for Scedosporium Species | 36.4 Response rate percentage |
Secondary
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.
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
Population: The mITT subpopulation contains all participants in the ITT set who had a DRC-adjudicated baseline infection due to Lomentospora prolificans.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Overall Response at Day 42 for Lomentospora Prolificans | 42.3 Response rate percentage |
Secondary
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
Population: The mITT subpopulation contains all participants in the ITT set who had a DRC-adjudicated baseline infection due to other olorofim susceptible fungi.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Overall Response at Day 42 for Other Olorofim Susceptible Fungi | 33.3 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT set who were assigned to a DRC-adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Overall Response at Day 84 | 27.2 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | At least 90 percent improvement | 11 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | At least 50 to less than 90 percent improvement | 10 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | At least 25 to less than 50 percent improvement | 12 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | Stable findings (0 to less than 25 percent improvement) | 55 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | Worsening response | 6 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | No signs on Radiological images at Screening | 7 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | Not evaluable | 75 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | Not relevant | 2 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | Missing | 0 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 42 | Death (from any cause) | 24 Participants |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | At least 90 percent improvement | 14 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | At least 50 to less than 90 percent improvement | 11 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | At least 25 to less than 50 percent improvement | 5 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | Stable findings (0 to less than 25 percent improvement) | 36 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | Worsening response | 6 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | No signs on Radiological images at Screening | 5 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | Not evaluable | 71 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | Not relevant | 2 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | Missing | 21 Participants |
| Olorofim (F901318) | DRC Adjudicated Radiological Response at Day 84 | Death (from any cause) | 31 Participants |
Secondary
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
Population: The mITT set contains all patients in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | Investigator Assessed Clinical Response at Day 42 | 53.5 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | Investigator Assessed Clinical Response at Day 84 | 56.4 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | Investigator Assessed Mycological Response at Day 42 | 25.7 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the Intent to Treat analysis set who were assigned to a Data Review Committee adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | Investigator Assessed Mycological Response at Day 84 | 31.7 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT set who were assigned to a DRC-adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | Investigator Assessed Overall Response at Day 42 | 24.8 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT set who were assigned to a DRC-adjudicated disease category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olorofim (F901318) | Investigator Assessed Overall Response at Day 84 | 29.7 Response rate percentage |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | At least 90 percent improvement | 10 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | At least 50 to less than 90 percent improvement | 20 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | At least 25 to less than 50 percent improvement | 20 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | Stable findings (0 to less than 25 percent improvement) | 29 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | Worsening response | 11 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | No signs on Radiological images at Screening | 3 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | Not evaluable | 69 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | Missing | 16 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 42 | Death (from any cause) | 24 Participants |
Secondary
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
Population: The mITT set contains all participants in the ITT analysis set who were assigned to a DRC adjudicated disease category.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | At least 90 percent improvement | 23 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | At least 50 to less than 90 percent improvement | 16 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | At least 25 to less than 50 percent improvement | 16 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | Stable findings (0 to less than 25 percent improvement) | 26 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | Worsening response | 10 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | No signs on Radiological images at Screening | 4 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | Not evaluable | 52 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | Missing | 24 Participants |
| Olorofim (F901318) | Investigator Assessed Radiological Response at Day 84 | Death (from any cause) | 31 Participants |