Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi (VITAL)

This study has been completed.
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00634049
First received: March 5, 2008
Last updated: June 9, 2016
Last verified: June 2016
Results First Received: December 2, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Aspergillosis
Invasive Fungal Infections
Intervention: Drug: isavuconazole

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Consenting adult participants with proven, probable or possible invasive aspergillosis and renally impaired (RI) or of participants with invasive fungal disease (IFD) caused by rare moulds, yeasts or dimorphic fungi meeting the inclusion and none of the exclusion criteria were considered for entry into the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Analysis and interpretation of the results was pathogen dependent and each pathogen was quite rare, therefore it was not feasible to enroll a sufficient number of participants in a randomized controlled trial to power the study adequately to allow statistical comparisons.

Reporting Groups
  Description
Isavuconazole Participants received a loading dose of isavuconazole, 200 mg three times a day administered intravenously (IV) or orally (PO) [or per os (PO)] 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 180 days; with an option for extended treatment under specified criteria.

Participant Flow:   Overall Study
    Isavuconazole  
STARTED     149  
COMPLETED     146  
NOT COMPLETED     3  
Never received study drug                 1  
Died prior to receiving study drug                 1  
Screening failure                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to Treat Population (ITT)

Reporting Groups
  Description
Isavuconazole Participants received a loading dose of isavuconazole, 200 mg three times a day administered intravenously (IV) or orally (PO) [or per os (PO)] 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 180 days; with an option for extended treatment under specified criteria.

Baseline Measures
    Isavuconazole  
Number of Participants  
[units: participants]
  146  
Age  
[units: years]
Mean (Standard Deviation)
  49.9  (16.78)  
Gender  
[units: participants]
 
Female     46  
Male     100  
Race (NIH/OMB)  
[units: participants]
 
American Indian or Alaska Native     0  
Asian     24  
Native Hawaiian or Other Pacific Islander     0  
Black or African American     10  
White     108  
More than one race     0  
Unknown or Not Reported     4  
Race/Ethnicity, Customized  
[units: participants]
 
Hispanic or Latino     22  
Not Hispanic or Latino     124  
Region of Enrollment  
[units: participants]
 
Brazil     20  
India     5  
Israel     21  
Lebanon     1  
Mexico     8  
Russian Federation     2  
Korea, Republic of     2  
Thailand     14  
Belgium     13  
Germany     4  
United States     56  
Therapy status  
[units: participants]
 
Primary Therapy     93  
Refractory     38  
Intolerant     12  
Missing     3  
Hematologic malignancy  
[units: participants]
 
Yes     63  
No     83  
Allogeneic Bone Marrow Transplant (BMT)/Hematopoietic Stem Cell Transplant (HSCT) [1]
[units: participants]
 
Yes     26  
No     120  
Uncontrolled malignancy [2]
[units: participants]
 
Yes     46  
No     100  
Neutropenic [3]
[units: participants]
 
Yes     38  
No     66  
Missing     42  
Corticosteroid use [4]
[units: participants]
 
Yes     35  
No     111  
T-cell immunosuppressant use [5]
[units: participants]
 
Yes     61  
No     48  
Missing     37  
[1] Allogeneic BMT/HSCT status was defined as yes for participants who noted allogeneic for type of transplant and bone marrow cells for type of cells on the primary underlying disease or condition electronic case report form (eCRF). Otherwise, allogeneic BMT/HSCT status equaled no.
[2] Uncontrolled malignancy status was defined as yes for participants who noted a malignancy for diagnosis and new diagnosis/active disease or relapse for present status on the primary underlying disease or condition eCRF. Otherwise, uncontrolled malignancy status equaled no.
[3] Baseline neutropenic status was defined as yes for patients who noted recently resolved or ongoing neutropenia among the list of host factors on the categorization of IFD eCRF. Baseline neutropenic status was defined as no for patients who completed the categorization of IFD eCRF and did not meet the criterion in the previous sentence. Otherwise, baseline neutropenic status was missing.
[4] Corticosteroid use was defined as yes for participants who were administered corticosteroids for 21 days out of 28 days leading up to first administration of study drug. Otherwise, corticosteroid use equaled no.
[5] T-cell immunosuppressant use was defined as yes for patients who noted treatment with other recognized T-cell immunosuppressants among the list of host factors on the categorization of IFD eCRF. Along with the investigators’ assessment, participants who took certain prior medications could have been considered based on the medical evaluation. T-cell immunosuppressant use was defined as no for participants who completed the categorization of IFD eCRF and did not meet the criterion in the previous sentences. Otherwise, T-cell immunosuppressant use was missing.



  Outcome Measures
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1.  Primary:   Crude Success Rate of Overall Outcome of Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and End of Treatment (EOT).   [ Time Frame: Day 42, 84 and End of Treatment (EOT [Day 180]) ]

2.  Secondary:   Crude Success Rate of Clinical Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT   [ Time Frame: Day 42, 84 and End of Treatment (EOT [Day 180]) ]

3.  Secondary:   Crude Success Rate of Mycological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT   [ Time Frame: Day 42, 84 and End of Treatment (EOT [Day 180]) ]

4.  Secondary:   Crude Success Rate of Radiological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT   [ Time Frame: Day 42, 84 and End of Treatment (EOT [Day 180]) ]

5.  Secondary:   Crude Success Rate of Clinical Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT   [ Time Frame: Day 42, Day 84 and End of Treatment (EOT [Day 180]) ]

6.  Secondary:   Crude Success Rate of Mycological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT   [ Time Frame: Day 42, Day 84 and End of Treatment (EOT [Day 180]) ]

7.  Secondary:   Crude Success Rate of Radiological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT   [ Time Frame: Day 42, Day 84 and End of Treatment (EOT [Day 180]) ]

8.  Secondary:   All-cause Mortality Through Day 42 and Day 84   [ Time Frame: Baseline to End of Treatment (EOT [Day 180]) ]

9.  Secondary:   Safety - Overall Number of TEAEs   [ Time Frame: From the first study drug administration until 28 days after the last dose of study drug ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Enrollment in the clinical study was suspended in January 2009 pending further characterization of newly identified impurities. After successful study completion resumption of enrollment started in April 2011 for the 9766-CL-0103/WSA-CS-003 study.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Vice President, Medical Head ID/IM/TX
Organization: Astellas Pharma Global Development, Inc.
phone: (224) 205-8800
e-mail: Astellas.resultsdisclosure@astellas.com



Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00634049     History of Changes
Other Study ID Numbers: 9766-CL-0103
WSA-CS-003 ( Other Identifier: Basilea Protocol ID )
2006-005003-33 ( EudraCT Number )
Study First Received: March 5, 2008
Results First Received: December 2, 2015
Last Updated: June 9, 2016
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Canada: Health Canada
South Africa: Medicines Control Council
Lebanon: Ministry of Public Health
Hungary: National Institute of Pharmacy
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Israel: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Mexico: Secretaria de Salud
Brazil: National Health Surveillance Agency
Russia: Ministry of Health of the Russian Federation
United States: Food and Drug Administration
India: Central Drugs Standard Control Organization
Egypt: Ministry of Health and Population
Thailand: Food and Drug Administration
Poland: The Central Register of Clinical Trials
South Korea: Korea Food and Drug Administration (KFDA)