Trial Outcomes & Findings for A Study to Evaluate Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis (IA) or Invasive Mucormycosis (IM) in Pediatric Participants (NCT NCT03816176)
NCT ID: NCT03816176
Last Updated: 2024-12-05
Results Overview
An AE is any untoward medical occurrence in a participant administered a study drug, which does not have to have a causal relationship with this treatment. It can be any unfavorable sign, symptom, or disease temporally associated with the use of a medicinal product. TEAE is defined as an AE observed after starting administration of the study drug through 30 days after the last dose.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
From first dose to 30 days after the last dose (maximum 210 Days)
Results posted on
2024-12-05
Participant Flow
A total of 31 pediatric participants diagnosed with invasive aspergillosis (IA) or invasive mucormycosis (IM) were enrolled and received isavuconazonium sulfate.
Male or female participant 1 year to \< 18 years of age diagnosed with IA or IM. A positive diagnosis was defined as proven, probable or possible invasive fungal infection (IFI) per the European Organisation for Research and Treatment of Cancer/Mycoses Study Group \[EORTC/MSG\], 2008 criteria.
Participant milestones
| Measure |
Isavuconazonium Sulfate
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
|
Overall Study
STARTED
|
31
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
| Measure |
Isavuconazonium Sulfate
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
|
Overall Study
Miscellaneous
|
5
|
|
Overall Study
Lack of Efficacy
|
4
|
|
Overall Study
Adverse Event
|
3
|
Baseline Characteristics
A Study to Evaluate Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis (IA) or Invasive Mucormycosis (IM) in Pediatric Participants
Baseline characteristics by cohort
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Age, Continuous
|
9.7 Years
STANDARD_DEVIATION 5.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From first dose to 30 days after the last dose (maximum 210 Days)Population: The safety analysis set (SAF) consisted of all participant who were enrolled and received at least one dose of study drug.
An AE is any untoward medical occurrence in a participant administered a study drug, which does not have to have a causal relationship with this treatment. It can be any unfavorable sign, symptom, or disease temporally associated with the use of a medicinal product. TEAE is defined as an AE observed after starting administration of the study drug through 30 days after the last dose.
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Number of Participants With Treatment Emergent Adverse Events (TEAEs)
|
29 Participants
|
PRIMARY outcome
Timeframe: Baseline up to 42 daysPopulation: FAS population
All - Cause Mortality Through Day 42
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Percentage of Participants With All - Cause Mortality Through Day 42
|
6.5 Percentage of participants
Interval 0.79 to 21.42
|
SECONDARY outcome
Timeframe: Baseline up to day 84 and end of treatment (EOT) (up to a maximum of 180 days) (Average duration of treatment: 57.7 days)Population: FAS population
EOT was defined as anytime from "day 1 to a maximum of day 180". Data reported in the table below for each category, i.e., Day 84 represented data between Day 1 and Day 84 and for EOT, data represented between Day 1 to the EOT day for each individual. Participants who died after EOT assessment but before reaching Day 84 were included in the data for Day 84 category. Only those deaths that occurred after Day 84 would be included in EOT category if the death occurred during the treatment period (i.e. prior to the EOT).
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Percentage of Participants With All - Cause Mortality
Day 84
|
9.7 Percentage of participants
Interval 2.04 to 25.75
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|
Percentage of Participants With All - Cause Mortality
EOT
|
0.00 Percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline up to days 42, 84 and EOT (180 days)Population: FAS population
Overall response was based on a composite of clinical, mycological, and radiological responses with success criteria assessed. Success criteria as assessed by AC in: Clinical response: * Complete: Resolution of all attributable clinical symptoms and physical findings * Partial: Resolution of at Least some of the clinical symptoms and physical findings associated with IFD Mycological response: * Eradication: No growth of the original (at baseline) causative organism on culture or identified by histology/cytology on post baseline (after day 7) cultures and/or histology/cytology * Presumed eradication: Missing post baseline documentation of eradication of the original causative organism at baseline PLUS resolution of all or some clinical symptoms/physical finding Radiological response: * Complete: ≥ 90% improvement * Partial: At least \< 25% response at day 42 and at least 50% by Day 84
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Percentage of Participants With Overall Response: Adjudication Committee (AC) Assessment
Day 84
|
25.8 Percentage of partticipants
|
|
Percentage of Participants With Overall Response: Adjudication Committee (AC) Assessment
EOT
|
54.8 Percentage of partticipants
|
|
Percentage of Participants With Overall Response: Adjudication Committee (AC) Assessment
Day 42
|
29.0 Percentage of partticipants
|
SECONDARY outcome
Timeframe: Baseline up to days 42, 84 and EOT (180 days)Population: FAS population. If participant did not reach Day 42 or Day 84 of therapy then the AC did not perform these assessments.
AC Assessed Clinical response was defined as follows: * Success: Complete (if resolution of all attributable clinical symptoms and physical findings occurs); Partial (if resolution of at least some of the clinical symptoms and physical findings associated with IFD) * Failure: Stable (if minor of no change in clinical symptoms and physical findings associated with IFD); Progression (if worsening or new clinical symptoms and physical findings associated with IFD, or if alternative systemic antifungal treatment is required) * Not Evaluable: If not assessed or no clinical signs or symptoms at baseline * No assessment: Those participants that do not fall under any of the above criteria
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Percentage of Participants With Clinical Response: AC Assessment
Day 42 Success
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
EOT No Assessment
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
Day 42 Failure
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
Day 42 Not Evaluable
|
58.06 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
Day 42 No Assessment
|
41.94 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
Day 84 Success
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
Day 84 Failure
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
Day 84 Not Evaluable
|
35.48 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
Day 84 No Assessment
|
64.52 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
EOT Success
|
6.45 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
EOT Failure
|
9.68 Percentage of participants
|
|
Percentage of Participants With Clinical Response: AC Assessment
EOT Not Evaluable
|
83.87 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to days 42, 84 and EOT (180 days)Population: FAS population. If participant did not reach Day 42 or Day 84 of therapy then the investigator did not perform these assessments.
Investigator-assessed Clinical Response was defined as follows: * Success: if resolution of all attributable signs and symptoms or resolution of attributable clinical symptoms and physical findings * Failure: if no resolution of any attributable signs and symptoms or no resolution of any attributable signs and symptoms (no change) or worsening of any attributable signs and symptoms * Not Evaluable: if results not available /participant unevaluable or if no attributable signs and symptoms * No assessment: Those participants that do not fall under any of the above criteria
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Percentage of Participants With Clinical Response: Investigator Assessment
Day 42 Success
|
41.9 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
Day 42 Failure
|
9.7 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
Day 42 Not Evaluable
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
Day 42 No Assessment
|
48.4 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
Day 84 Success
|
32.3 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
Day 84 Failure
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
Day 84 Not Evaluable
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
Day 84 No Assessment
|
67.7 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
EOT Success
|
61.3 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
EOT Failure
|
29.0 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
EOT Not Evaluable
|
3.2 Percentage of participants
|
|
Percentage of Participants With Clinical Response: Investigator Assessment
EOT No Assessment
|
6.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to days 42, 84 and EOT (180 days)Population: FAS population. If participant did not reach Day 42 or Day 84 of therapy then the AC did not perform these assessments.
AC-assessed Radiological Response was defined as follows: * Success: Complete (if ≥ 90% improvement); Partial (if at least \< 25% response at day 42 and at least 50% response by Day 84) * Failure: Stable (if minor or no change in radiographic abnormalities associated with IFD, but no signs of progression); Progression (if worsening or new radiological abnormalities associated with IRD) * Not Evaluable: if no post baseline radiology available with baseline evidence of radiolical disease Or Radiology not applicable at baseline * No assessment: Those participants that do not fall under any of the above criteria
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Percentage of Participants With Radiological Response: AC Assessment
Day 42 Success
|
29.03 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
Day 42 Failure
|
6.45 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
Day 42 Not Evaluable
|
22.58 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
Day 42 No Assessment
|
41.94 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
Day 84 Success
|
25.81 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
Day 84 Failure
|
0 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
Day 84 Not Evaluable
|
9.68 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
Day 84 No Assessment
|
64.52 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
EOT Success
|
51.61 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
EOT Failure
|
16.13 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
EOT Not Evaluable
|
32.26 Percentage of participants
|
|
Percentage of Participants With Radiological Response: AC Assessment
EOT No Assessment
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to days 42, 84 and EOT (180 days)Population: FAS population. If participant did not reach Day 42 or Day 84 of therapy then the investigator did not perform these assessments.
Investigator's assessed radiological response was defined as follows: * Success: if ≥ 90% improvement, ≥ 50% to \< 90% improvement, ≥ 25% to 50% improvement (for Day 42 only) * Failure if \< 25% improvement at any time or no signs or radiological Images * Not Evaluable if results not evaluable or no radiological data available * No assessment: Those participants that do not fall under any of the above criteria
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
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|---|---|
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Percentage of Participants With Radiological Response: Investigator Assessment
Day 42 No Assessment
|
58.1 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
Day 84 Success
|
19.4 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
Day 84 Failure
|
0 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
Day 84 Not Evaluable
|
9.7 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
Day 42 Success
|
25.8 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
Day 84 No Assessment
|
71.0 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
Day 42 Failure
|
3.2 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
Day 42 Not Evaluable
|
12.9 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
EOT Success
|
48.4 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
EOT Failure
|
16.1 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
EOT Not Evaluable
|
29.0 Percentage of participants
|
|
Percentage of Participants With Radiological Response: Investigator Assessment
EOT No Assessment
|
6.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to days 42, 84 and EOT (180 days)Population: FAS population. If participant did not reach Day 42 or Day 84 of therapy then the AC did not perform these assessments.
AC assessed mycological response was defined as follows: * Success: Eradicated (no growth of the original \[at baseline\] causative organism on culture or identified by histology/cytology on post baseline \[after day 7\] cultures and/or histology/cytology); Presumed Eradicated (missing post baseline documentation of eradication of the original causative organism at baseline PLUS resolution of all or some clinical symptoms/physical finding) * Failure: Persistence (persistence of the original causative organism cultured or identified by histological /cytology at baseline); Presumed Persistence (missing post baseline documentation of the persistence of the original causative organism at baseline PLUS no resolution or worsening of any clinical symptoms/physical findings) * Not Evaluable - no mycological evidence * No assessment: Those participants that do not fall under any of the above criteria
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
|
|---|---|
|
Percentage of Participants With Mycological Response: AC Assessment
Day 42 Failure
|
3.23 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
Day 42 Success
|
19.35 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
Day 42 Not Evaluable
|
35.48 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
Day 42 No Assessment
|
41.94 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
Day 84 Success
|
19.35 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
Day 84 Failure
|
0 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
Day 84 Not Evaluable
|
16.13 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
Day 84 No Assessment
|
64.52 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
EOT Success
|
35.48 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
EOT Failure
|
12.90 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
EOT Not Evaluable
|
51.61 Percentage of participants
|
|
Percentage of Participants With Mycological Response: AC Assessment
EOT No Assessment
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to days 42, 84 and EOT (180 days)Population: FAS population. If participant did not reach Day 42 or Day 84 of therapy then the investigator did not perform these assessments.
Investigator's assessed mycological response was defined as follows: * Success: Eradicated (no growth of the original \[at baseline\] causative organism on culture or identified by histology/cytology on post baseline \[after day 7\] cultures and/or histology/cytology); Presumed Eradicated (missing post baseline documentation of eradication of the original causative organism at baseline PLUS resolution of all or some clinical symptoms/physical finding) * Failure: Persistence (persistence of the original causative organism cultured or identified by histological /cytology at baseline); Presumed Persistence (missing post baseline documentation of the persistence of the original causative organism at baseline PLUS no resolution or worsening of any clinical symptoms/physical findings) * Not Evaluable: Indeterminate/no mycological follow-up or results available * No assessment: Those participants that do not fall under any of the above criteria
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=31 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
|
|---|---|
|
Percentage of Participats With Mycological Response: Investigator Assessment
Day 42 Success
|
22.6 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
Day 42 Failure
|
6.5 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
Day 42 Not Evaluable
|
22.6 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
Day 42 No Assessment
|
48.4 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
Day 84 Success
|
25.8 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
Day 84 Failure
|
0 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
EOT Success
|
45.2 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
Day 84 Not Evaluable
|
3.2 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
Day 84 No Assessment
|
71.0 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
EOT Failure
|
12.9 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
EOT Not Evaluable
|
35.5 Percentage of Participants
|
|
Percentage of Participats With Mycological Response: Investigator Assessment
EOT No Assessment
|
6.5 Percentage of Participants
|
SECONDARY outcome
Timeframe: Predose on days 7, and 14Population: The pharmacokinetic analysis set (PKAS) consisted of all participants who took at least one dose of study drug and who had at least one plasma concentration.
Ctrough was defined as the predose concentration at the end of dosing interval.
Outcome measures
| Measure |
Isavuconazonium Sulfate
n=28 Participants
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
|
|---|---|
|
Pharmacokinetics of Isavuconazonium Sulphate in Plasma: Trough Concentration (Ctrough)
Age group 12 to <18 Day 7
|
3862.2 Nanograms/milliter (ng/mL)
Standard Deviation 1427.1
|
|
Pharmacokinetics of Isavuconazonium Sulphate in Plasma: Trough Concentration (Ctrough)
Age group 1 to <6 Day 7
|
2965.0 Nanograms/milliter (ng/mL)
Standard Deviation 1770.5
|
|
Pharmacokinetics of Isavuconazonium Sulphate in Plasma: Trough Concentration (Ctrough)
Age group 1 to <6 Day 14
|
2286.7 Nanograms/milliter (ng/mL)
Standard Deviation 1991.3
|
|
Pharmacokinetics of Isavuconazonium Sulphate in Plasma: Trough Concentration (Ctrough)
Age group 6 to <12 Day 7
|
3732.7 Nanograms/milliter (ng/mL)
Standard Deviation 1855.0
|
|
Pharmacokinetics of Isavuconazonium Sulphate in Plasma: Trough Concentration (Ctrough)
Age group 6 to <12 Day 14
|
3623.3 Nanograms/milliter (ng/mL)
Standard Deviation 1878.0
|
|
Pharmacokinetics of Isavuconazonium Sulphate in Plasma: Trough Concentration (Ctrough)
Age group 12 to <18 Day 14
|
4380.0 Nanograms/milliter (ng/mL)
Standard Deviation 2022.4
|
Adverse Events
Isavuconazonium Sulfate
Serious events: 18 serious events
Other events: 28 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Isavuconazonium Sulfate
n=31 participants at risk
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
6.5%
2/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Cardiac disorders
Cardio-respiratory arrest
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Cardiac disorders
Pericardial effusion
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Ear and labyrinth disorders
Ear pain
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Abdominal distension
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Stomatitis
|
6.5%
2/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
General disorders
Infusion site pain
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
General disorders
Infusion site pruritus
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
General disorders
Injection site reaction
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Hepatobiliary disorders
Venoocclusive liver disease
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Immune system disorders
Graft versus host disease
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Bacteraemia
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Bacterial sepsis
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Brain abscess
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Escherichia sepsis
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Pneumococcal sepsis
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Pneumonia
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Pneumonia pseudomonal
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Sepsis
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Septic shock
|
9.7%
3/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Streptococcal sepsis
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Vascular device infection
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.2%
1/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Musculoskeletal and connective tissue disorders
Synovitis
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Renal and urinary disorders
Anuria
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Social circumstances
Social problem
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Vascular disorders
Circulatory collapse
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Vascular disorders
Hypertension
|
3.2%
1/31 • Number of events 1 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
Other adverse events
| Measure |
Isavuconazonium Sulfate
n=31 participants at risk
Participants received 10 mg/kg dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion)followed by once-daily maintenance dose of 10 mg/kg for up to 84 days for IA or 180 days for IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
9.7%
3/31 • Number of events 6 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Blood and lymphatic system disorders
Lymphopenia
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.5%
2/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Cardiac disorders
Tachycardia
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Ear and labyrinth disorders
Ear pain
|
6.5%
2/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Abdominal distension
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Abdominal pain
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Aphthous ulcer
|
12.9%
4/31 • Number of events 7 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Constipation
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Diarrhoea
|
25.8%
8/31 • Number of events 9 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Nausea
|
12.9%
4/31 • Number of events 8 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Stomatitis
|
16.1%
5/31 • Number of events 6 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Gastrointestinal disorders
Vomiting
|
22.6%
7/31 • Number of events 14 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
General disorders
Chills
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
General disorders
Non-cardiac chest pain
|
16.1%
5/31 • Number of events 5 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
General disorders
Pain
|
6.5%
2/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
General disorders
Pyrexia
|
29.0%
9/31 • Number of events 13 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Immune system disorders
Drug hypersensitivity
|
6.5%
2/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
COVID-19
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Folliculitis
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Oral herpes
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Infections and infestations
Rhinitis
|
9.7%
3/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Investigations
QRS axis abnormal
|
6.5%
2/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Investigations
Transaminases increased
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.5%
2/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
12.9%
4/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
12.9%
4/31 • Number of events 7 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.5%
2/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Nervous system disorders
Headache
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Renal and urinary disorders
Dysuria
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.7%
3/31 • Number of events 4 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Lung opacity
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.5%
2/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
6.5%
2/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Vascular disorders
Hypertension
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Vascular disorders
Hypotension
|
9.7%
3/31 • Number of events 3 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
|
Vascular disorders
Pallor
|
6.5%
2/31 • Number of events 2 • From first dose to 30 days after the last dose (maximum 210 days)
SAF popuation
|
Additional Information
Clinical Transparency
Astellas Pharma Global Development, Inc
Phone: 8008887704
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
- Publication restrictions are in place
Restriction type: OTHER