Isavuconazole (BAL8557) for Primary Treatment of Invasive Aspergillosis

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00412893
First received: December 18, 2006
Last updated: March 19, 2015
Last verified: March 2015
  Purpose

The purpose of this study is to compare the efficacy and safety of isavuconazole versus voriconazole in the treatment of patients with invasive aspergillosis.


Condition Intervention Phase
Invasive Fungal Infection
Aspergillosis
Drug: Isavuconazole
Drug: Voriconazole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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.

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • All-cause Mortality Through Day 42 [ Time Frame: Through Day 42 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]

Enrollment: 527
Study Start Date: March 2007
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Isavuconazole
Loading doses were administered as IV infusion and maintenance doses were administered as IV infusion or oral (capsules).
Other Names:
  • ASP9766
  • BAL8557
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.
Drug: Voriconazole
Loading doses were administered as IV infusion and maintenance doses were administered as IV infusion or oral (capsules).
Other Name: VFend

Detailed Description:

Acute invasive fungal infections caused by aspergillus, zygomycetes and other filamentous fungi remain life threatening diseases. Early treatment with highly effective anti-fungals reduces mortality. This study investigates the efficacy and safety of isavuconazole in the treatment of invasive fungal diseases, caused by Aspergillus or other filamentous fungi.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00412893

  Show 107 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Basilea Pharmaceutica International Ltd
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00412893     History of Changes
Other Study ID Numbers: 9766-CL-0104, WSA-CS-004, 2006-003868-59
Study First Received: December 18, 2006
Results First Received: March 19, 2015
Last Updated: March 19, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
China: Food and Drug Administration
Egypt: Ministry of Health and Population
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
Israel: Ministry of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Lebanon: Ministry of Public Health
Mexico: Secretaria de Salud
Malaysia: Ministry of Health
New Zealand: Medsafe
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: The Central Register of Clinical Trials
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Thailand: Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
Phase III
Invasive fungal disease
Aspergillus species
Filamentous fungi
ASP9766
BAL8557
Isavuconazole

Additional relevant MeSH terms:
Aspergillosis
Mycoses
Dermatomycoses
Hyalohyphomycosis
Infection
Skin Diseases
Skin Diseases, Infectious
Voriconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 27, 2015