Invasive Pulmonary Aspergillosis
Conditions
Keywords
Aspergillosis, SCY-078, Ibrexafungerp, Coadministration
Brief summary
Study to evaluate the safety and efficacy of coadminstration of SCY-078 with a mold-active azole (voriconazole) compared to voriconazole in patients with invasive pulmonary aspergillosis.
Detailed description
This is a multicenter, randomized, double-blind, two-arm study to evaluate the safety, tolerability, efficacy and PK of the coadministration of SCY-078 plus voriconazole compared to those of voriconazole in male and female subjects 18 years of age and older with a probable or proven invasive pulmonary aspergillosis.
Interventions
DRUGSCY-078
Oral tablets of SCY-078
DRUGVoriconazole
Voriconazole IV vials or oral tablets
OTHEROral Placebo Tablets
Oral Placebo Tablets matching SCY-078
Sponsors
Scynexis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject is a male or female adult ≥18 years of age on the day the study informed consent form (ICF) is signed. 2. Subject has a probable or proven IPA based on the protocol-specified criteria (Section 22.3) that requires antifungal treatment. Note: Subjects with possible IPA may enter the screening phase of the study but will only be randomized after meeting criteria for probable or proven IPA. 3. Subject has a result of a serum GMI from a sample obtained within the 96 hours preceding enrollment into the study (Baseline/Treatment Day 1). 4. Subject has a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation OR 5. Subject who either recently resolved or ongoing neutropenia (neutropenia defined as absolute neutrophil count \< 0.5 x 10⁹/L \[\< 500/mm³\] for \> 10 days), temporally related to the onset of fungal disease OR 6. Subject who received treatment with other recognized T-cell immunosuppressants (such as cyclosporine, tacrolimus, monoclonal antibodies or nucleoside analogs) during the past 90 days including solid organ transplant patients OR 7. Subject with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency) 8. Subject has not received more than 4 days (96 hours) of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study (Baseline/Treatment Day 1). However, subjects who have received more than 4 days but less than 7 days of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study may be enrolled but will require approval from the study medical monitor, who will evaluate each subject on a case-by-case basis. 9. Subject has an IPA episode that, in the investigator´s judgement, requires antifungal therapy and may be adequately treated with voriconazole (i.e., the IPA is not a breakthrough infection while receiving a mold-active azole antifungal \[voriconazole, posaconazole, isavuconazole or itraconazole\] that requires therapy with a non-azole antifungal agent).
Exclusion criteria
1. Subject has a fungal disease with central nervous system involvement suspected at Screening. 2. Subject is receiving, has received or anticipates to be receiving concomitant medications that are listed in the prohibited medication list (Appendix A in full protocol) within the specified washout periods. 3. Subject has a Karnofsky score \<20. 4. Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed. 5. Subject is under mechanical ventilation. 6. Subject has abnormal liver test parameters: AST or ALT \>5 x ULN and/or total bilirubin \>2.5 x ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Up to a maximum of 19 weeks | Number of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Died (Any Cause) | At Day 42 and Day 84 | Number and Percentage of participants who died (any cause) |
| Change in Serum Galactomannan Index (GMI) | Weeks 1, 2, 4 and 6 | Absolute change in serum GMI from from baseline to each time point (Weeks 1, 2, 4 and 6). Negative values indicate a reduction of GMI (i.e., improvement). |
| Percent of Participants With Changes in GMI | Weeks 1, 2, 4 and 6 from Baseline | Percentage of participants with the following changes in GMI values from Baseline: * Fifty percent reduction or greater at Weeks 1, 2, 4 and 6 * Twenty-five percent reduction or greater at Weeks 1, 2, 4 and 6 * Any percent reduction at Weeks 1, 2, 4 and 6 * Reduction equal to or greater than 0.25 at Weeks 1, 2, 4 and 6 * Reduction to \< 0.5 at Weeks 1, 2, 4 and 6 |
| Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC) | At end of treatment (up to 13 weeks), day 42 and day 84 | Number and percentage of participants with Complete Response or Partial Response as determined by the Data Review Committee (DRC). Complete Response: Survival and resolution of all attributable symptoms and signs of disease; plus, successful radiological outcome; plus, mycological eradication. Partial Response: Survival and partial resolution of attributable symptoms and signs of disease; plus, improvement (at least 25%) of radiological lesions; plus, mycological eradication. |
| Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | End of Treatment (EoT), Day 42 and Day 84 | Percentage of participants with: * Clinical Response at EoT, Day 42 and Day 84, as determined by the DRC * Mycological Response at EoT, Day 42 and Day 84, as determined by the DRC * Radiological Response at EoT, Day 42 and Day 84, as determined by the DRC |
| Percentage of Participants With a Clinical, Mycological and Radiological Response. | End of Treatment (EoT), Day 42 and Day 84 | Percentage of participants with: * Clinical Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator * Mycological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator * Radiological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator |
| SCY-078 and Voriconazole Plasma Concentrations | Treatment Days 7 and 14 (2-4 hrs post dose) | Voriconazole and SCY-078 plasma concentrations (ng/mL) |
| Time to Achieve Serum GMI Change From Baseline | Up to a maximum of 19 weeks | Time (days) to achieve the following changes in serum GMI from Baseline: * Fifty percent reduction * Twenty-five percent reduction * Any percent reduction * Reduction equal to or greater than 0.25 |
Countries
Belgium, Canada, Germany, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCY-078 Plus Voriconazole Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks. | 10 |
| Voriconazole Mono-therapy Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks. | 12 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Voriconazole Mono-therapy | Total | SCY-078 Plus Voriconazole |
|---|---|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 14.08 | 62.2 years STANDARD_DEVIATION 12.33 | 61.7 years STANDARD_DEVIATION 10.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 19 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 18 Participants | 8 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 10 Participants | 17 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 10 | 1 / 12 |
| other Total, other adverse events | 10 / 10 | 11 / 12 |
| serious Total, serious adverse events | 6 / 10 | 5 / 12 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths
Number of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths.
Time frame: Up to a maximum of 19 weeks
Population: Safety population including any participant treated with at least one dose of Voriconazole or SCY-078
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SCY-078 Plus Voriconazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Number of participants with treatment emergent adverse events | 10 participants |
| SCY-078 Plus Voriconazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Number of participants with treatment-related adverse events | 4 participants |
| SCY-078 Plus Voriconazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Number of participants discontinued due to adverse event | 2 participants |
| SCY-078 Plus Voriconazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Number of participants who died | 3 participants |
| Voriconazole Mono-therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Number of participants who died | 1 participants |
| Voriconazole Mono-therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Number of participants with treatment emergent adverse events | 11 participants |
| Voriconazole Mono-therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Number of participants discontinued due to adverse event | 4 participants |
| Voriconazole Mono-therapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths | Number of participants with treatment-related adverse events | 0 participants |
Secondary
Change in Serum Galactomannan Index (GMI)
Absolute change in serum GMI from from baseline to each time point (Weeks 1, 2, 4 and 6). Negative values indicate a reduction of GMI (i.e., improvement).
Time frame: Weeks 1, 2, 4 and 6
Population: Participants who have a probable or proven invasive pulmonary aspergillosis at baseline, per DRC, with at least one positive serum GMI at baseline and at least one GMI value at Weeks 1, 2, 4 and/or 6.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| SCY-078 Plus Voriconazole | Change in Serum Galactomannan Index (GMI) | Week 1 | -0.1870 index |
| SCY-078 Plus Voriconazole | Change in Serum Galactomannan Index (GMI) | Week 2 | -0.5240 index |
| SCY-078 Plus Voriconazole | Change in Serum Galactomannan Index (GMI) | Week 4 | -0.7500 index |
| SCY-078 Plus Voriconazole | Change in Serum Galactomannan Index (GMI) | Week 6 | -0.9950 index |
| Voriconazole Mono-therapy | Change in Serum Galactomannan Index (GMI) | Week 6 | -0.9570 index |
| Voriconazole Mono-therapy | Change in Serum Galactomannan Index (GMI) | Week 1 | -0.4910 index |
| Voriconazole Mono-therapy | Change in Serum Galactomannan Index (GMI) | Week 4 | -0.9570 index |
| Voriconazole Mono-therapy | Change in Serum Galactomannan Index (GMI) | Week 2 | -0.4080 index |
Secondary
Percentage of Participants Who Died (Any Cause)
Number and Percentage of participants who died (any cause)
Time frame: At Day 42 and Day 84
Population: Intent-to-Treat (ITT) Population including all randomized participants who received at least one dose of randomized study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCY-078 Plus Voriconazole | Percentage of Participants Who Died (Any Cause) | Day 42 | 1 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants Who Died (Any Cause) | Day 84 | 3 Participants |
| Voriconazole Mono-therapy | Percentage of Participants Who Died (Any Cause) | Day 42 | 1 Participants |
| Voriconazole Mono-therapy | Percentage of Participants Who Died (Any Cause) | Day 84 | 1 Participants |
Secondary
Percentage of Participants With a Clinical, Mycological and Radiological Response.
Percentage of participants with: * Clinical Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator * Mycological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator * Radiological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
Time frame: End of Treatment (EoT), Day 42 and Day 84
Population: Intent-to-Treat (ITT) Population including all randomized participants who received at least one dose of randomized study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Clinical Response at Day 42 | 6 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Mycological Response at Day 84 | 1 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Mycological Response at EoT | 7 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Radiological Response at EoT | 7 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Clinical Response at Day 84 | 1 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Radiological Response at Day 42 | 5 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Mycological Response at Day 42 | 6 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Radiological Response at Day 84 | 1 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Clinical Response at EoT | 8 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Radiological Response at Day 84 | 0 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Clinical Response at EoT | 10 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Clinical Response at Day 42 | 9 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Clinical Response at Day 84 | 0 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Mycological Response at EoT | 11 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Mycological Response at Day 42 | 8 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Mycological Response at Day 84 | 0 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Radiological Response at EoT | 10 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response. | Radiological Response at Day 42 | 8 Participants |
Secondary
Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC
Percentage of participants with: * Clinical Response at EoT, Day 42 and Day 84, as determined by the DRC * Mycological Response at EoT, Day 42 and Day 84, as determined by the DRC * Radiological Response at EoT, Day 42 and Day 84, as determined by the DRC
Time frame: End of Treatment (EoT), Day 42 and Day 84
Population: Intent-to-Treat (ITT) Population including all randomized participants who received at least one dose of randomized study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Clinical Response at Day 42 | 4 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Mycological Response at Day 84 | 4 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Mycological Response at EoT | 7 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Radiological Response at EoT | 7 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Clinical Response at Day 84 | 3 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Radiological Response at Day 42 | 5 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Mycological Response at Day 42 | 6 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Radiological Response at Day 84 | 4 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Clinical Response at EoT | 6 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Radiological Response at Day 84 | 5 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Clinical Response at EoT | 9 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Clinical Response at Day 42 | 7 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Clinical Response at Day 84 | 4 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Mycological Response at EoT | 9 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Mycological Response at Day 42 | 7 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Mycological Response at Day 84 | 4 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Radiological Response at EoT | 9 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC | Radiological Response at Day 42 | 7 Participants |
Secondary
Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC)
Number and percentage of participants with Complete Response or Partial Response as determined by the Data Review Committee (DRC). Complete Response: Survival and resolution of all attributable symptoms and signs of disease; plus, successful radiological outcome; plus, mycological eradication. Partial Response: Survival and partial resolution of attributable symptoms and signs of disease; plus, improvement (at least 25%) of radiological lesions; plus, mycological eradication.
Time frame: At end of treatment (up to 13 weeks), day 42 and day 84
Population: Intent-to-Treat (ITT) Population including all randomized participants who received at least one dose of randomized study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCY-078 Plus Voriconazole | Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC) | Participants with Complete or Partial Response at End of Treatment | 7 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC) | Participants with Complete or Partial Response at Day 42 | 4 Participants |
| SCY-078 Plus Voriconazole | Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC) | Participants with Complete or Partial Response at Day 84 | 4 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC) | Participants with Complete or Partial Response at End of Treatment | 9 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC) | Participants with Complete or Partial Response at Day 42 | 6 Participants |
| Voriconazole Mono-therapy | Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC) | Participants with Complete or Partial Response at Day 84 | 4 Participants |
Secondary
Percent of Participants With Changes in GMI
Percentage of participants with the following changes in GMI values from Baseline: * Fifty percent reduction or greater at Weeks 1, 2, 4 and 6 * Twenty-five percent reduction or greater at Weeks 1, 2, 4 and 6 * Any percent reduction at Weeks 1, 2, 4 and 6 * Reduction equal to or greater than 0.25 at Weeks 1, 2, 4 and 6 * Reduction to \< 0.5 at Weeks 1, 2, 4 and 6
Time frame: Weeks 1, 2, 4 and 6 from Baseline
Population: Modified Intent-to-treat (mITT) population including participants who have a probable or proven invasive pulmonary aspergillosis at baseline, per DRC, with at least one positive serum GMI at baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 1 : Fifty percent reduction or greater | 0 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 1 : Twenty-five percent reduction or greater | 2 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 1 : Any percent reduction | 4 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 1 : Reduction equal to or greater than 0.25 | 2 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 1 : Reduction to < 0.5 | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 2 : Fifty percent reduction or greater | 2 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 2 : Twenty-five percent reduction | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 2 : Any percent reduction | 4 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 2 : Reduction equal to or greater than 0.25 | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 2 : Reduction to < 0.5 | 2 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 4 : Fifty percent reduction or greater | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 4 : Twenty-five percent reduction | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 4 : Any percent reduction | 5 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 4 : Reduction equal to or greater than 0.25 | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 4 : Reduction to < 0.5 | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 6 : Fifty percent reduction or greater | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 6 : Twenty-five percent reduction | 4 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 6 : Any percent reduction | 4 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 6 : Reduction equal to or greater than 0.25 | 3 Participants |
| SCY-078 Plus Voriconazole | Percent of Participants With Changes in GMI | Week 6 : Reduction to < 0.5 | 2 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 6 : Any percent reduction | 4 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 1 : Fifty percent reduction or greater | 1 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 4 : Fifty percent reduction or greater | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 1 : Twenty-five percent reduction or greater | 4 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 6 : Fifty percent reduction or greater | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 1 : Any percent reduction | 4 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 4 : Twenty-five percent reduction | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 1 : Reduction equal to or greater than 0.25 | 4 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 6 : Reduction to < 0.5 | 1 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 1 : Reduction to < 0.5 | 2 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 4 : Any percent reduction | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 2 : Fifty percent reduction or greater | 2 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 6 : Twenty-five percent reduction | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 2 : Twenty-five percent reduction | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 4 : Reduction equal to or greater than 0.25 | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 2 : Any percent reduction | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 6 : Reduction equal to or greater than 0.25 | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 2 : Reduction equal to or greater than 0.25 | 3 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 4 : Reduction to < 0.5 | 0 Participants |
| Voriconazole Mono-therapy | Percent of Participants With Changes in GMI | Week 2 : Reduction to < 0.5 | 1 Participants |
Secondary
SCY-078 and Voriconazole Plasma Concentrations
Voriconazole and SCY-078 plasma concentrations (ng/mL)
Time frame: Treatment Days 7 and 14 (2-4 hrs post dose)
Population: Participants of study who provide a PK sample
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SCY-078 Plus Voriconazole | SCY-078 and Voriconazole Plasma Concentrations | Day 7 SCY-078 Concentration | 1432.30 nanograms per milliliter (ng/mL) | Standard Deviation 455.59 |
| SCY-078 Plus Voriconazole | SCY-078 and Voriconazole Plasma Concentrations | Day 14 SCY-078 Concentration | 1312.03 nanograms per milliliter (ng/mL) | Standard Deviation 422.53 |
| SCY-078 Plus Voriconazole | SCY-078 and Voriconazole Plasma Concentrations | Day 7 Voriconazole Concentration | 2609.73 nanograms per milliliter (ng/mL) | Standard Deviation 2060.43 |
| SCY-078 Plus Voriconazole | SCY-078 and Voriconazole Plasma Concentrations | Day 14 Voriconazole Concentration | 2074.24 nanograms per milliliter (ng/mL) | Standard Deviation 1201.28 |
| Voriconazole Mono-therapy | SCY-078 and Voriconazole Plasma Concentrations | Day 14 Voriconazole Concentration | 2963.49 nanograms per milliliter (ng/mL) | Standard Deviation 1583.51 |
| Voriconazole Mono-therapy | SCY-078 and Voriconazole Plasma Concentrations | Day 7 Voriconazole Concentration | 2891.72 nanograms per milliliter (ng/mL) | Standard Deviation 1557.2 |
Secondary
Time to Achieve Serum GMI Change From Baseline
Time (days) to achieve the following changes in serum GMI from Baseline: * Fifty percent reduction * Twenty-five percent reduction * Any percent reduction * Reduction equal to or greater than 0.25
Time frame: Up to a maximum of 19 weeks
Population: Intent-to-treat (ITT) population including participants who have a probable or proven invasive pulmonary aspergillosis at baseline, per DRC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SCY-078 Plus Voriconazole | Time to Achieve Serum GMI Change From Baseline | Fifty percent reduction | 28.00 Days |
| SCY-078 Plus Voriconazole | Time to Achieve Serum GMI Change From Baseline | Twenty-five percent reduction | 14.00 Days |
| SCY-078 Plus Voriconazole | Time to Achieve Serum GMI Change From Baseline | Any percent reduction | 5.00 Days |
| SCY-078 Plus Voriconazole | Time to Achieve Serum GMI Change From Baseline | Reduction equal to or greater than 0.25 | NA Days |
| Voriconazole Mono-therapy | Time to Achieve Serum GMI Change From Baseline | Reduction equal to or greater than 0.25 | NA Days |
| Voriconazole Mono-therapy | Time to Achieve Serum GMI Change From Baseline | Fifty percent reduction | 29.00 Days |
| Voriconazole Mono-therapy | Time to Achieve Serum GMI Change From Baseline | Any percent reduction | 3.50 Days |
| Voriconazole Mono-therapy | Time to Achieve Serum GMI Change From Baseline | Twenty-five percent reduction | 5.50 Days |