Isavuconazole (BAL8557) for Primary Treatment of Invasive Aspergillosis
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| ClinicalTrials.gov Identifier: NCT00412893 |
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Recruitment Status :
Completed
First Posted : December 19, 2006
Results First Posted : March 31, 2015
Last Update Posted : April 5, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Aspergillosis Invasive Fungal Infection | Drug: Isavuconazole Drug: Voriconazole | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 527 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Double Blind, Randomized Study to Evaluate Safety and Efficacy of BAL8557 Versus Voriconazole for Primary Treatment of Invasive Fungal Disease Caused by Aspergillus Species or Other Filamentous Fungi. |
| Actual Study Start Date : | March 7, 2007 |
| Actual Primary Completion Date : | March 28, 2013 |
| Actual Study Completion Date : | March 28, 2013 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Isavuconazole
Participants received a loading dose of isavuconazole, 200 mg three times a day by intravenous infusion (IV) for the first 2 days followed by a maintenance dose from Day 3 of 200 mg once daily either IV or orally until they reached a treatment endpoint or for a maximum of 84 days.
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Drug: Isavuconazole
Loading doses were administered as IV infusion and maintenance doses were administered as IV infusion or oral (capsules).
Other Names:
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Active Comparator: Voriconazole
Participants received a loading dose of voriconazole, 6 mg/kg every 12 hours IV for the first 24 hours, followed by a maintenance dose of 4 mg/kg every 12 hours by IV on Day 2. Beginning on Day 3, participants received 4 mg/kg every 12 hours by IV or 200 mg every 12 hours orally, until they reached a treatment endpoint or for a maximum of 84 days.
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Drug: Voriconazole
Loading doses were administered as IV infusion and maintenance doses were administered as IV infusion or oral (capsules).
Other Name: VFend |
- All-cause Mortality Through Day 42 [ Time Frame: Through Day 42 ]All-cause mortality is represented as the percentage of participants who died after first dose of study drug through Day 42 from any cause. Participants with unknown survival status through Day 42 were included as deaths in the calculation.
- Percentage of Participants With an Overall Outcome of Success Evaluated by the Data Review Committee (DRC) [ Time Frame: Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days. ]
The DRC was an independent, blinded committee consisting of experts in the field of infectious disease who assessed patients' outcomes. The overall response was based on the DRC-assessed clinical, mycological and radiological responses.
Success was defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings, the eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline and a > 50% improvement in radiological response from Baseline (or improvement of at least 25% from Baseline for the Day 42 analysis or End of Treatment if it occurred prior to Day 42).
End of treatment (EOT) is the last day of study drug administration. For the Day 42 and Day 84 analyses, any visits that the DRC assessed as Not Done were considered a failure for that visit. A death before Day 42 was also considered a failure, even if the DRC assessed the participant to be a success prior to death.
- All-cause Mortality Through Day 84 [ Time Frame: Through Day 84 ]All-cause mortality is represented as the percentage of participants who died after first dose of study drug through Day 84 from any cause. Participants with unknown survival status through Day 84 were included as deaths in the calculation.
- Percentage of Participants With an Overall Outcome of Success Evaluated by Investigator [ Time Frame: Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days. ]Overall response based on investigators' assessments was not derived as it was not deemed necessary because participants overall response status was determined by the DRC. All investigators' assessments of clinical, mycological and radiological responses are analyzed separately (see Outcome Measures 8-10).
- Percentage of Participants With a Clinical Response Assessed by the DRC [ Time Frame: Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days. ]
Blinded assessments of clinical symptoms and physical findings of invasive fungal disease were performed by the independent DRC.
Clinical response is defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings. Failure is defined as no resolution of any attributable clinical symptoms and physical findings and/or worsening. Participants with no attributable signs and symptoms present at Baseline and no symptoms attributable to invasive fungal disease (IFD) developed post-baseline were classified as "Not Applicable." End of treatment is the last day of study drug administration.
- Percentage of Participants With a Mycological Response Assessed by the DRC [ Time Frame: Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days. ]
Blinded mycological assessments of the participant's invasive fungal disease status were performed by the independent DRC using the results from fungal culture and isolation and/or histology/cytology of biopsy or biological fluid samples from the infected site.
Mycological response is defined as eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline. Failure was defined as persistence or presumed persistence. Participants with no mycological evidence available at Baseline were classified as "Not Applicable".
End of treatment is the last day of study drug administration.
- Percentage of Participants With a Radiological Response Assessed by the DRC [ Time Frame: Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days. ]
Independent reviews of radiology assessments were completed by radiology experts which were provided to the independent, blinded DRC. Blinded radiological assessments were performed by the DRC.
Radiological response is defined as a ≥ 50% improvement from Baseline, or improvement of at least 25% from Baseline for the Day 42 analysis or if end of treatment occurred before Day 42. Participants without any radiology at Baseline were considered "Not Applicable." End of Treatment is the last day of study drug administration.
- Percentage of Participants With a Clinical Response Assessed by the Investigator [ Time Frame: Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days. ]
Assessment of clinical symptoms and physical findings of invasive fungal disease were performed by the investigator.
Clinical response is defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings. Failure is defined as no resolution of any attributable clinical symptoms and physical findings and/or worsening, or if results were unavailable or the participant was unevaluable. Participants with no attributable signs and symptoms present at Baseline were classified as "Not Applicable." End of treatment is the last day of study drug administration.
- Percentage of Participants With a Mycological Response Assessed by the Investigator [ Time Frame: Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days. ]
Mycological assessments of the participant's invasive fungal disease status were performed by the investigator using the results from fungal culture and isolation and/or histology/cytology of biopsy or biological fluid samples from the infected site.
Mycological response is defined as eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline. Failure was defined as persistence or presumed persistence. Participants with no mycological evidence available at Baseline, or no mycological follow-up results available or indeterminate results were classified as "Not Applicable".
End of treatment is the last day of study drug administration.
- Percentage of Participants With a Radiological Response Assessed by the Investigator [ Time Frame: Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days. ]Radiological assessments were performed by the investigator. Radiological response is defined as a ≥ 50% improvement from Baseline, or improvement of at least 25% from Baseline for the Day 42 analysis or if end of treatment occurred before Day 42. Failure is defined as a < 25% improvement at any time or results not available. Participants with no signs on radiological images at Baseline were considered "Not Applicable." End of Treatment is the last day of study drug administration.
- Number of Participants With Adverse Events, Reported by System Organ Class [ Time Frame: From the first study drug administration until 28 days after the last dose of study drug. The median duration of study drug administration was 45 days. ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients must have proven, probable or possible invasive fungal disease caused by Aspergillus species or other filamentous fungi
- Female patients must be non-lactating and at no risk for pregnancy
Exclusion Criteria:
- Patients with invasive fungal infections other than Aspergillus species or other filamentous fungi
- Evidence of hepatic dysfunction at Baseline or moderate to severe renal dysfunction
- Patients with chronic aspergillosis, or aspergilloma or allergic bronchopulmonary aspergillosis
- Patients who have received more than 4 days of systemic antifungal therapy other than fluconazole within the 7 days prior to the first administration of study medication
- Patients previously enrolled in a Phase III study with isavuconazole
- Patients with a body weight </= 40 kg
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00412893
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| Study Director: | Medical Director | Astellas Pharma Global Development |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Astellas Pharma Inc |
| ClinicalTrials.gov Identifier: | NCT00412893 |
| Other Study ID Numbers: |
9766-CL-0104 WSA-CS-004 ( Other Identifier: Basilea Protocol ID ) 2006-003868-59 ( EudraCT Number ) |
| First Posted: | December 19, 2006 Key Record Dates |
| Results First Posted: | March 31, 2015 |
| Last Update Posted: | April 5, 2019 |
| Last Verified: | March 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data. |
| Access Criteria: | Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement. |
| URL: | https://www.clinicalstudydatarequest.com/ |
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Invasive fungal disease BAL8557 Isavuconazole ASP9766 |
Filamentous fungi Phase III Aspergillus species |
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Mycoses Aspergillosis Invasive Fungal Infections Bacterial Infections and Mycoses Infections Voriconazole Isavuconazole Antifungal Agents Anti-Infective Agents |
14-alpha Demethylase Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Steroid Synthesis Inhibitors Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Cytochrome P-450 CYP3A Inhibitors |