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

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ClinicalTrials.gov Identifier: NCT00634049
Recruitment Status : Completed
First Posted : March 12, 2008
Results First Posted : January 11, 2016
Last Update Posted : January 2, 2018
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Aspergillosis
Invasive Fungal Infections
Intervention Drug: isavuconazole
Enrollment 149
Recruitment Details 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 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.
Arm/Group Title Isavuconazole
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 149
Completed 146
Not Completed 3
Reason Not Completed
Never received study drug             1
Died prior to receiving study drug             1
Screening failure             1
Arm/Group Title Isavuconazole
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 146
Hide Baseline Analysis Population Description
Intent to Treat Population (ITT)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 146 participants
49.9  (16.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 146 participants
Female
46
  31.5%
Male
100
  68.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 146 participants
American Indian or Alaska Native
0
   0.0%
Asian
24
  16.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
10
   6.8%
White
108
  74.0%
More than one race
0
   0.0%
Unknown or Not Reported
4
   2.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants
Hispanic or Latino 22
Not Hispanic or Latino 124
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants
Primary Therapy 93
Refractory 38
Intolerant 12
Missing 3
Hematologic malignancy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants
Yes 63
No 83
Allogeneic Bone Marrow Transplant (BMT)/Hematopoietic Stem Cell Transplant (HSCT)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants
Yes 26
No 120
[1]
Measure Description: 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.
Uncontrolled malignancy   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants
Yes 46
No 100
[1]
Measure Description: 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.
Neutropenic   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants
Yes 38
No 66
Missing 42
[1]
Measure Description: 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.
Corticosteroid use   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants
Yes 35
No 111
[1]
Measure Description: 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.
T-cell immunosuppressant use   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants
Yes 61
No 48
Missing 37
[1]
Measure Description: 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.
1.Primary Outcome
Title Crude Success Rate of Overall Outcome of Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and End of Treatment (EOT).
Hide Description

The DRC assessed overall response based on individual clinical, mycological and radiological response assessments. Overall response outcomes were described as Success (complete or partial). Complete success was defined as a resolution of all clinical symptoms and physical findings associated with IFD. Partial success was defined as a resolution of at least some clinical symptoms and physical findings associated with IFD

End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Time Frame Day 42, 84 and End of Treatment (EOT [Day 180])
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-To-Treat population (mITT)
Arm/Group Title mITT - Aspergillus [Renally Impaired] mITT - Aspergillus [Not Renally Impaired] mITT - Mucorales (Primary Therapy) mITT - Mucorales (Refractory) mITT - Mucorales (Intolerant) mITT- Other Filamentous Fungi mITT- Other Mould Species Only mITT- Other Dimorphic Fungi mITT- Other Non-Candida Yeast mITT-Other Mixed Infection
Hide Arm/Group Description:
Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired and not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for patients who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).
Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.
Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior antifungal therapy (AFT)
Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior antifungal therapy (AFT).
Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).
Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.
Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).
Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).
Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Overall Number of Participants Analyzed 20 4 21 11 5 17 7 29 11 15
Measure Type: Number
Unit of Measure: percentage of participants
Day 42- Success Rate 25.0 50.0 14.3 9.1 0 47.1 28.6 41.4 36.4 13.3
Day 84 - Success Rate 30.0 25.0 9.5 36.4 20.0 41.2 28.6 44.8 36.4 13.3
End of Treatment (EOT) - Success Rate 30.0 66.7 31.6 36.4 20.0 64.7 28.6 64.3 72.7 14.3
2.Secondary Outcome
Title Crude Success Rate of Clinical Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
Hide Description

The DRC evaluated clinical response to treatment at day 42, day 84 and EOT. Clinical response outcomes were described as Success [Resolution of all attributable clinical symptoms and physical findings and Partial resolution of attributable clinical symptoms and physical findings].

End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Time Frame Day 42, 84 and End of Treatment (EOT [Day 180])
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-To-Treat population (mITT)
Arm/Group Title mITT - Aspergillus [Renally Impaired] mITT - Aspergillus [Not Renally Impaired] mITT - Mucorales (Primary Therapy) mITT - Mucorales (Refractory) mITT - Mucorales (Intolerant) mITT-Other Filamentous Fungi mITT- Other Mould Species Only mITT- Other Dimorphic Fungi mITT- Other Non-Candida Yeast mITT-Other Mixed Infection
Hide Arm/Group Description:
Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired or not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for patients who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).
Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.
Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT.
Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.
Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).
Other Mould Species mITT population consisted of 7 participants who have had proven or probable IFD as determined by the DRC caused by mould species.
Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).
Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).
Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Overall Number of Participants Analyzed 20 4 21 11 5 17 7 29 11 15
Measure Type: Number
Unit of Measure: percentage of participants
Day 42- Success Rate 55.0 75.0 50.0 33.3 50.0 68.8 71.4 79.3 70.0 42.9
Day 84 - Success Rate 45.0 25.0 40.0 22.2 50.0 62.5 42.9 82.8 70.0 35.7
End of Treatment (EOT) - Success Rate 55.0 66.7 55.6 22.2 50.0 81.3 85.7 82.1 70.0 38.5
3.Secondary Outcome
Title Crude Success Rate of Mycological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
Hide Description

The DRC evaluated mycological response to treatment at day 42, day 84 and EOT. Mycological response outcomes were described as Success [Eradication and Presumed eradication].

End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Time Frame Day 42, 84 and End of Treatment (EOT [Day 180])
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-To-Treat population (mITT)
Arm/Group Title mITT - Aspergillus [Renally Impaired] mITT - Aspergillus [Not Renally Impaired] mITT - Mucorales (Primary Therapy) mITT - Mucorales (Refractory) mITT - Mucorales (Intolerant) mITT-Other Filamentous Fungi mITT- Other Mould Species Only mITT- Other Dimorphic Fungi mITT- Other Non-Candida Yeast mITT-Other Mixed Infection
Hide Arm/Group Description:
Aspergillus - Renally Impaired mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participants IFD. The Aspergillus-mITT population was presented by renal status, renally impaired and not renally impaired. Renal impairment was defined as yes for participants who have a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for participants who have a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).
Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.
Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT.
Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.
Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).
Other Mould Species mITT population consisted of 7 participants who have had proven or probable IFD as determined by the DRC caused by mould species.
Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).
Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).
Other Mixed Infections mITT population consisted of 15 participants who have had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Overall Number of Participants Analyzed 20 4 21 11 5 17 7 29 11 15
Measure Type: Number
Unit of Measure: percentage of participants
Day 42- Success Rate 30.0 50.0 4.8 0 0 29.4 28.6 27.6 45.5 13.3
Day 84 - Success Rate 35.0 25.0 9.5 27.3 40.0 35.3 28.6 27.6 45.5 13.3
End of Treatment (EOT) - Success Rate 35.0 66.7 31.6 36.4 40.0 70.6 28.6 53.6 81.8 14.3
4.Secondary Outcome
Title Crude Success Rate of Radiological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
Hide Description

The DRC evaluated radiological response to treatment at at day 42, day 84 and EOT. Radiological response outcomes were described as Success [Improvement of at least 25% from baseline for invasive aspergillosis and other filamentous mold infections], [Improvement of at least 50% from baseline for invasive aspergillosis and other filamentous mold infections]; and [Improvement of at least 25% from baseline if EOT occurs prior to day 42 and at least 50% improvement from baseline if EOT occurs after day 42 for invasive aspergillosis and other filamentous mold infections].

End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Time Frame Day 42, 84 and End of Treatment (EOT [Day 180])
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-To-Treat population (mITT)
Arm/Group Title mITT - Aspergillus [Renally Impaired] mITT - Aspergillus [Not Renally Impaired] mITT - Mucorales (Primary Therapy) mITT - Mucorales (Refractory) mITT - Mucorales (Intolerant) mITT-Other Filamentous Fungi mITT- Other Mould Species Only mITT- Other Dimorphic Fungi mITT- Other Non-Candida Yeast mITT-Other Mixed Infection
Hide Arm/Group Description:
Aspergillus - Renally Impaired mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participants IFD. The Aspergillus-mITT population was presented by renal status, renally impaired and not renally impaired. Renal impairment was defined as yes for participants who have a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for participants who have a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).
Aspergillus - Renally Impaired mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participants IFD. The Aspergillus-mITT population was presented by renal status, renally impaired and not renally impaired. Overall there were 24 participants in the mITTAspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Mucorales – Primary Therapy mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.
Mucorales – Refractory Therapy mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT.
Mucorales – Intolerant mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.
Other Filamentous Fungi mITT population consisted of 17 participants who have had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium,2 Exophiala,2 Cladosporium,2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia,Exserohilum, Paecilomyces,Pseudallescheria and Scedosporium).
Other Mould Species mITT population consisted of 7 participants who have had proven or probable IFD as determined by the DRC caused by mould species.
Other Dimorphic Fungi mITT population consisted of 29 participants who have had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes,9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).
Other Non Candida Yeast mITT population consisted of 11 participants who have had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus NOS and 2 Trichosporon).
Other Mixed Infections mITT population consisted of 15 participants who have had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Overall Number of Participants Analyzed 20 4 21 11 5 17 7 29 11 15
Measure Type: Number
Unit of Measure: percentage of participants
Day 42- Success Rate 30.0 25.0 0 10.0 0 25.0 16.7 21.4 0 7.1
Day 84 - Success Rate 20.0 25.0 4.8 20.0 20.0 6.3 0 28.6 10.0 14.3
End of Treatment (EOT) - Success Rate 15.0 66.7 16.7 20.0 20.0 50.0 0 33.3 10.0 7.7
5.Secondary Outcome
Title Crude Success Rate of Clinical Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
Hide Description

The Investigator evaluated clinical response to treatment at day 42, day 84 and EOT. Clinical response outcomes were described as Success [Resolution of all attributable clinical symptoms and physical findings] and [Resolution of some attributable clinical symptoms and physical findings].

End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Time Frame Day 42, Day 84 and End of Treatment (EOT [Day 180])
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-To-Treat population (mITT)
Arm/Group Title mITT - Aspergillus [Renally Impaired] mITT - Aspergillus [Not Renally Impaired] mITT - Mucorales (Primary Therapy) mITT - Mucorales (Refractory) mITT - Mucorales (Intolerant) mITT- Other Filamentous Fungi mITT- Other Mould Species Only mITT- Other Dimorphic Fungi mITT- Other Non-Candida Yeast mITT-Other Mixed Infection
Hide Arm/Group Description:
Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired and not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for participants who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).
Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.
Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT
Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.
Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).
Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.
Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).
Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).
Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Overall Number of Participants Analyzed 20 4 21 11 5 17 7 29 11 15
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 60.0 75.0 50.0 28.6 25.0 81.3 85.7 75.9 70.0 50.0
Day 84 55.0 55.0 21.4 25.0 20.0 62.5 42.9 82.2 70.0 35.7
End of Treatment (EOT) 60.0 75.0 42.9 28.6 66.7 81.3 71.4 79.3 70.0 42.9
6.Secondary Outcome
Title Crude Success Rate of Mycological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
Hide Description

The Investigator evaluated mycological response to treatment at day 42, day 84 and EOT. Mycological response outcomes were described as Success [Eradication,Presumed eradication].

End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Time Frame Day 42, Day 84 and End of Treatment (EOT [Day 180])
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Hide Analysis Population Description
Modified Intent-To-Treat population (mITT)
Arm/Group Title mITT - Aspergillus [Renally Impaired] mITT - Aspergillus [Not Renally Impaired] mITT - Mucorales (Primary Therapy) mITT - Mucorales (Refractory) mITT - Mucorales (Intolerant) mITT- Other Filamentous Fungi mITT- Other Mould Species Only mITT- Other Dimorphic Fungi mITT- Other Non-Candida Yeast mITT-Other Mixed Infection
Hide Arm/Group Description:
Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired and not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for patients who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).
Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.
Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT
Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.
Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).
Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.
Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).
Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).
Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Overall Number of Participants Analyzed 20 4 21 11 2 17 7 29 11 15
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 46.7 66.7 50.0 28.6 25.0 69.2 83.3 70.6 50.0 18.2
Day 84 44.4 50.0 21.4 25.0 20.0 64.3 42.9 80.0 25.0 33.3
End of Treatment (EOT) 50.0 66.7 42.9 28.6 66.7 78.6 66.7 76.9 50.0 25.0
7.Secondary Outcome
Title Crude Success Rate of Radiological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
Hide Description

The Investigator evaluated radiological response to treatment at day 42, day 84 and EOT. Radiological response outcomes were described as Success [≥ 90% improvement,≥ 50% to < 90% improvement and ≥ 25% to < 50% improvement (for day 42 and EOT, if EOT occurs prior to day 42)].

End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Time Frame Day 42, Day 84 and End of Treatment (EOT [Day 180])
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Hide Analysis Population Description
Modified Intent-To-Treat population (mITT)
Arm/Group Title mITT - Aspergillus [Renally Impaired] mITT - Aspergillus [Not Renally Impaired] mITT - Mucorales (Primary Therapy) mITT - Mucorales (Refractory) mITT - Mucorales (Intolerant) mITT- Other Filamentous Fungi mITT- Other Mould Species Only mITT- Other Dimorphic Fungi mITT- Other Non-Candida Yeast mITT-Other Mixed Infection
Hide Arm/Group Description:
Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired and not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for participants who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).
Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.
Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT
Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.
Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).
Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.
Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).
Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).
Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Overall Number of Participants Analyzed 20 4 21 11 5 17 7 29 11 15
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 35.0 75.0 40.0 0 40.0 46.7 20.0 32.1 9.1 28.6
Day 84 40.0 50.0 25.0 11.1 40.0 40.0 20.0 37.0 0 7.1
End of Treatment (EOT) 35.0 50.0 30.0 22.2 20.0 33.3 40.0 55.6 10.0 14.3
8.Secondary Outcome
Title All-cause Mortality Through Day 42 and Day 84
Hide Description

All-cause Mortality was assessed through Day 42 and Day 84 and summarized for ITT population

End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Time Frame Baseline to End of Treatment (EOT [Day 180])
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Hide Analysis Population Description
Intent-To-Treat population (ITT)
Arm/Group Title Renally Impaired Not Renally Impaired
Hide Arm/Group Description:
Renally Impaired (RI) population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. Renal impairment was defined as yes for participants who had a baseline eGFR-MDRD < 60 mL/min/1.73 m^2, no for patients who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).
Not Renally Impaired (NRI) population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Overall Number of Participants Analyzed 59 87
Measure Type: Number
Unit of Measure: percentage of participants
All-cause Mortality Through Day 42 22.0 16.1
All-cause Mortality Through Day 84 30.5 20.7
9.Secondary Outcome
Title Safety - Overall Number of TEAEs
Hide Description A Treatment Emergent Adverse Events (TEAE) is any adverse event that starts after the first administration of study drug until 28 days after the last dose of study drug.
Time Frame From the first study drug administration until 28 days after the last dose of study drug
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Hide Analysis Population Description
The safety analysis set (SAF) consists of all enrolled participants who received at least one dose of study drug as this was a non-comparative open-label study
Arm/Group Title Isavuconazole
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Participants received Isavuconazole intravenous (IV) or per oral (PO) over period of 2 days, on days 1 and 2 three doses of 200 mg were administered every 8 hours for a total of six doses. From Day 3 to End of Treatment (EOT) maintenance dose of 200 mg isavuconazole was administered once daily up to 180 days; with an option for extended treatment under specified criteria.
Overall Number of Participants Analyzed 146
Measure Type: Number
Unit of Measure: participants
TEAEs 139
Study Drug-Related TEAEs 60
Serious TEAEs 89
Study Drug-Related Serious TEAEs 13
TEAEs Leading to Permanent Discontinuation of Stud 19
Study Drug TEAEs Leading to Perm Discontinuation 7
TEAEs Leading to Death 44
Study Drug-Related TEAEs Leading to Death 1
Deaths 47
Deaths Through 28 Days after Last Dose Study Drug 42
Time Frame From the first administration of study drug until 28 days after the last dose of study drug. For the days when IV and oral doses were administered on the same day, the day was split into one-half day for each route’s duration.
Adverse Event Reporting Description The safety analysis set is identical to the intent -to-treat (ITT) population (i.e., all enrolled participants who received at least one dose of study drug) as this was a non-comparative open-label study.
 
Arm/Group Title Renally Impaired (RI) Not Renally Impaired (NRI)
Hide Arm/Group Description Renal impairment was defined as yes for participants who have a baseline as eGFR < 60 mL/min/1.73 m^2 by the Modification of Diet in Renal Disease (MDRD) formula.

Not Renally impaired participants were defined as no if they have a baseline eGFR-MDRD

≥ 60 mL/min/1.73 m^2 by the Modification of Diet in Renal Disease (MDRD) formula.

All-Cause Mortality
Renally Impaired (RI) Not Renally Impaired (NRI)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Renally Impaired (RI) Not Renally Impaired (NRI)
Affected / at Risk (%) Affected / at Risk (%)
Total   43/59 (72.88%)   46/87 (52.87%) 
Blood and lymphatic system disorders     
Anaemia  1  1/59 (1.69%)  1/87 (1.15%) 
Febrile neutropenia  1  1/59 (1.69%)  1/87 (1.15%) 
Pancytopenia  1  0/59 (0.00%)  1/87 (1.15%) 
Cardiac disorders     
Acute myocardial infarction  1  1/59 (1.69%)  0/87 (0.00%) 
Atrial fibrillation  1  2/59 (3.39%)  0/87 (0.00%) 
Atrioventricular block complete  1  1/59 (1.69%)  0/87 (0.00%) 
Cardiac failure acute  1  0/59 (0.00%)  1/87 (1.15%) 
Cardio-respiratory arrest  1  1/59 (1.69%)  1/87 (1.15%) 
Electromechanical dissociation  1  1/59 (1.69%)  0/87 (0.00%) 
Eye disorders     
Retinal artery occlusion  1  0/59 (0.00%)  1/87 (1.15%) 
Retinal haemorrhage  1  1/59 (1.69%)  0/87 (0.00%) 
Vitreous haemorrhage  1  1/59 (1.69%)  0/87 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  2/59 (3.39%)  3/87 (3.45%) 
Colitis  1  0/59 (0.00%)  1/87 (1.15%) 
Colitis ulcerative  1  0/59 (0.00%)  1/87 (1.15%) 
Constipation  1  1/59 (1.69%)  0/87 (0.00%) 
Diarrhoea  1  1/59 (1.69%)  1/87 (1.15%) 
Dysphagia  1  1/59 (1.69%)  1/87 (1.15%) 
Gastrointestinal haemorrhage  1  3/59 (5.08%)  0/87 (0.00%) 
Localised intraabdominal fluid collection  1  0/59 (0.00%)  1/87 (1.15%) 
Nausea  1  0/59 (0.00%)  2/87 (2.30%) 
Oesophagitis  1  0/59 (0.00%)  1/87 (1.15%) 
Pancreatitis  1  0/59 (0.00%)  1/87 (1.15%) 
Pancreatitis chronic  1  0/59 (0.00%)  1/87 (1.15%) 
Pancreatitis relapsing  1  0/59 (0.00%)  1/87 (1.15%) 
Vomiting  1  0/59 (0.00%)  4/87 (4.60%) 
General disorders     
Death  1  1/59 (1.69%)  2/87 (2.30%) 
General physical health deterioration  1  1/59 (1.69%)  0/87 (0.00%) 
Multi-organ failure  1  0/59 (0.00%)  1/87 (1.15%) 
Non-cardiac chest pain  1  1/59 (1.69%)  1/87 (1.15%) 
Oedema peripheral  1  1/59 (1.69%)  0/87 (0.00%) 
Pyrexia  1  1/59 (1.69%)  1/87 (1.15%) 
Hepatobiliary disorders     
Acute hepatic failure  1  0/59 (0.00%)  1/87 (1.15%) 
Cholangiolitis  1  1/59 (1.69%)  0/87 (0.00%) 
Cholecystitis  1  1/59 (1.69%)  0/87 (0.00%) 
Cholelithiasis  1  1/59 (1.69%)  0/87 (0.00%) 
Liver disorder  1  0/59 (0.00%)  1/87 (1.15%) 
Immune system disorders     
Acute graft versus host disease  1  2/59 (3.39%)  0/87 (0.00%) 
Graft versus host disease  1  1/59 (1.69%)  1/87 (1.15%) 
Lung transplant rejection  1  0/59 (0.00%)  1/87 (1.15%) 
Infections and infestations     
Abdominal abscess  1  0/59 (0.00%)  1/87 (1.15%) 
Appendicitis  1  0/59 (0.00%)  1/87 (1.15%) 
Aspergillosis  1  1/59 (1.69%)  2/87 (2.30%) 
BK virus infection  1  1/59 (1.69%)  0/87 (0.00%) 
Bacteraemia  1  3/59 (5.08%)  0/87 (0.00%) 
Bacterial sepsis  1  1/59 (1.69%)  0/87 (0.00%) 
Brain abscess  1  1/59 (1.69%)  0/87 (0.00%) 
Bronchiectasis  1  0/59 (0.00%)  1/87 (1.15%) 
Bronchiolitis  1  1/59 (1.69%)  0/87 (0.00%) 
Catheter site infection  1  0/59 (0.00%)  1/87 (1.15%) 
Clostridium difficile colitis  1  1/59 (1.69%)  0/87 (0.00%) 
Cytomegalovirus enteritis  1  0/59 (0.00%)  1/87 (1.15%) 
Cytomegalovirus infection  1  1/59 (1.69%)  1/87 (1.15%) 
Empyema  1  1/59 (1.69%)  0/87 (0.00%) 
Enterococcal bacteraemia  1  0/59 (0.00%)  1/87 (1.15%) 
Escherichia bacteraemia  1  0/59 (0.00%)  1/87 (1.15%) 
Escherichia sepsis  1  1/59 (1.69%)  0/87 (0.00%) 
Fungal infection  1  0/59 (0.00%)  1/87 (1.15%) 
Fungal sepsis  1  1/59 (1.69%)  0/87 (0.00%) 
Gastroenteritis norovirus  1  1/59 (1.69%)  0/87 (0.00%) 
Gastroenteritis viral  1  0/59 (0.00%)  1/87 (1.15%) 
Herpes zoster  1  0/59 (0.00%)  2/87 (2.30%) 
Influenza  1  0/59 (0.00%)  1/87 (1.15%) 
Lung infection  1  0/59 (0.00%)  1/87 (1.15%) 
Lung infection pseudomonal  1  1/59 (1.69%)  0/87 (0.00%) 
Mucormycosis  1  0/59 (0.00%)  2/87 (2.30%) 
Pneumocystis jiroveci pneumonia  1  1/59 (1.69%)  0/87 (0.00%) 
Pneumonia  1  1/59 (1.69%)  6/87 (6.90%) 
Pneumonia bacterial  1  1/59 (1.69%)  2/87 (2.30%) 
Pneumonia blastomyces  1  1/59 (1.69%)  0/87 (0.00%) 
Pneumonia fungal  1  0/59 (0.00%)  2/87 (2.30%) 
Pneumonia influenzal  1  1/59 (1.69%)  0/87 (0.00%) 
Pneumonia primary atypical  1  1/59 (1.69%)  0/87 (0.00%) 
Pseudomonal sepsis  1  0/59 (0.00%)  2/87 (2.30%) 
Pseudomonas bronchitis  1  1/59 (1.69%)  0/87 (0.00%) 
Sepsis  1  2/59 (3.39%)  1/87 (1.15%) 
Septic shock  1  6/59 (10.17%)  0/87 (0.00%) 
Sinusitis  1  1/59 (1.69%)  0/87 (0.00%) 
Sinusitis fungal  1  0/59 (0.00%)  1/87 (1.15%) 
Staphylococcal bacteraemia  1  1/59 (1.69%)  0/87 (0.00%) 
Staphylococcal infection  1  0/59 (0.00%)  1/87 (1.15%) 
Staphylococcal sepsis  1  0/59 (0.00%)  1/87 (1.15%) 
Streptococcal bacteraemia  1  0/59 (0.00%)  1/87 (1.15%) 
Subcutaneous abscess  1  0/59 (0.00%)  1/87 (1.15%) 
Urinary tract infection  1  1/59 (1.69%)  0/87 (0.00%) 
Urosepsis  1  1/59 (1.69%)  0/87 (0.00%) 
Viral diarrhoea  1  1/59 (1.69%)  0/87 (0.00%) 
Zygomycosis  1  0/59 (0.00%)  2/87 (2.30%) 
Metabolism and nutrition disorders     
Dehydration  1  2/59 (3.39%)  1/87 (1.15%) 
Hyperkalaemia  1  1/59 (1.69%)  0/87 (0.00%) 
Hypoglycaemia  1  0/59 (0.00%)  1/87 (1.15%) 
Hyponatraemia  1  0/59 (0.00%)  1/87 (1.15%) 
Malnutrition  1  0/59 (0.00%)  1/87 (1.15%) 
Musculoskeletal and connective tissue disorders     
Arthritis  1  0/59 (0.00%)  1/87 (1.15%) 
Musculoskeletal chest pain  1  2/59 (3.39%)  0/87 (0.00%) 
Pain in extremity  1  1/59 (1.69%)  0/87 (0.00%) 
Systemic lupus erythematosus  1  0/59 (0.00%)  1/87 (1.15%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute lymphocytic leukaemia recurrent  1  0/59 (0.00%)  1/87 (1.15%) 
Acute myeloid leukaemia  1  2/59 (3.39%)  0/87 (0.00%) 
Acute myeloid leukaemia recurrent  1  0/59 (0.00%)  2/87 (2.30%) 
Chronic lymphocytic leukaemia  1  0/59 (0.00%)  1/87 (1.15%) 
Malignant neoplasm progression  1  0/59 (0.00%)  2/87 (2.30%) 
Leukaemia recurrent  1  1/59 (1.69%)  0/87 (0.00%) 
Leukaemic infiltration  1  1/59 (1.69%)  0/87 (0.00%) 
Nervous system disorders     
Aphasia  1  1/59 (1.69%)  0/87 (0.00%) 
Cerebral infarction  1  2/59 (3.39%)  1/87 (1.15%) 
Cerebrovascular accident  1  1/59 (1.69%)  0/87 (0.00%) 
Convulsion  1  0/59 (0.00%)  2/87 (2.30%) 
Haemorrhagic transformation stroke  1  1/59 (1.69%)  0/87 (0.00%) 
Headache  1  0/59 (0.00%)  1/87 (1.15%) 
Hemiparesis  1  1/59 (1.69%)  0/87 (0.00%) 
Transient ischaemic attack  1  0/59 (0.00%)  1/87 (1.15%) 
Psychiatric disorders     
Abnormal behaviour  1  1/59 (1.69%)  0/87 (0.00%) 
Aggression  1  1/59 (1.69%)  0/87 (0.00%) 
Agitation  1  1/59 (1.69%)  0/87 (0.00%) 
Confusional state  1  1/59 (1.69%)  0/87 (0.00%) 
Hallucination  1  1/59 (1.69%)  0/87 (0.00%) 
Renal and urinary disorders     
Renal failure  1  1/59 (1.69%)  0/87 (0.00%) 
Renal failure acute  1  6/59 (10.17%)  2/87 (2.30%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  1/59 (1.69%)  0/87 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/59 (1.69%)  0/87 (0.00%) 
Acute respiratory failure  1  0/59 (0.00%)  3/87 (3.45%) 
Dyspnoea  1  0/59 (0.00%)  1/87 (1.15%) 
Haemoptysis  1  1/59 (1.69%)  1/87 (1.15%) 
Hypercapnia  1  0/59 (0.00%)  1/87 (1.15%) 
Hypoxia  1  1/59 (1.69%)  0/87 (0.00%) 
Pleural effusion  1  0/59 (0.00%)  1/87 (1.15%) 
Pneumonia aspiration  1  1/59 (1.69%)  1/87 (1.15%) 
Pulmonary alveolar haemorrhage  1  1/59 (1.69%)  0/87 (0.00%) 
Pulmonary embolism  1  0/59 (0.00%)  1/87 (1.15%) 
Pulmonary infarction  1  1/59 (1.69%)  0/87 (0.00%) 
Pulmonary oedema  1  0/59 (0.00%)  1/87 (1.15%) 
Respiratory failure  1  4/59 (6.78%)  1/87 (1.15%) 
Sinus disorder  1  0/59 (0.00%)  1/87 (1.15%) 
Tachypnoea  1  0/59 (0.00%)  1/87 (1.15%) 
Wheezing  1  0/59 (0.00%)  1/87 (1.15%) 
Vascular disorders     
Arteritis  1  1/59 (1.69%)  0/87 (0.00%) 
Deep vein thrombosis  1  1/59 (1.69%)  1/87 (1.15%) 
Hypotension  1  2/59 (3.39%)  0/87 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Renally Impaired (RI) Not Renally Impaired (NRI)
Affected / at Risk (%) Affected / at Risk (%)
Total   54/59 (91.53%)   68/87 (78.16%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  4/59 (6.78%)  2/87 (2.30%) 
Neutropenia  1  6/59 (10.17%)  2/87 (2.30%) 
Cardiac disorders     
Atrial fibrillation  1  4/59 (6.78%)  1/87 (1.15%) 
Sinus tachycardia  1  3/59 (5.08%)  2/87 (2.30%) 
Tachycardia  1  4/59 (6.78%)  4/87 (4.60%) 
Gastrointestinal disorders     
Abdominal pain  1  7/59 (11.86%)  4/87 (4.60%) 
Abdominal pain upper  1  1/59 (1.69%)  5/87 (5.75%) 
Constipation  1  5/59 (8.47%)  10/87 (11.49%) 
Diarrhoea  1  16/59 (27.12%)  10/87 (11.49%) 
Haematochezia  1  3/59 (5.08%)  1/87 (1.15%) 
Nausea  1  19/59 (32.20%)  14/87 (16.09%) 
Stomatitis  1  3/59 (5.08%)  0/87 (0.00%) 
Vomiting  1  16/59 (27.12%)  17/87 (19.54%) 
General disorders     
Asthenia  1  1/59 (1.69%)  7/87 (8.05%) 
Chills  1  5/59 (8.47%)  3/87 (3.45%) 
Fatigue  1  4/59 (6.78%)  2/87 (2.30%) 
Oedema peripheral  1  8/59 (13.56%)  8/87 (9.20%) 
Pain  1  3/59 (5.08%)  2/87 (2.30%) 
Pyrexia  1  9/59 (15.25%)  15/87 (17.24%) 
Infections and infestations     
Clostridial infection  1  3/59 (5.08%)  0/87 (0.00%) 
Clostridium difficile colitis  1  3/59 (5.08%)  1/87 (1.15%) 
Herpes zoster  1  1/59 (1.69%)  5/87 (5.75%) 
Upper respiratory tract infection  1  5/59 (8.47%)  6/87 (6.90%) 
Urinary tract infection  1  7/59 (11.86%)  2/87 (2.30%) 
Investigations     
Blood alkaline phosphatase increased  1  3/59 (5.08%)  2/87 (2.30%) 
Gamma-glutamyltransferase increased  1  4/59 (6.78%)  6/87 (6.90%) 
Metabolism and nutrition disorders     
Decreased appetite  1  4/59 (6.78%)  6/87 (6.90%) 
Hyperglycaemia  1  3/59 (5.08%)  4/87 (4.60%) 
Hyperkalaemia  1  7/59 (11.86%)  4/87 (4.60%) 
Hypernatraemia  1  3/59 (5.08%)  1/87 (1.15%) 
Hypocalcaemia  1  3/59 (5.08%)  3/87 (3.45%) 
Hypokalaemia  1  6/59 (10.17%)  6/87 (6.90%) 
Hypomagnesaemia  1  2/59 (3.39%)  7/87 (8.05%) 
Hypophosphataemia  1  3/59 (5.08%)  0/87 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  6/59 (10.17%)  8/87 (9.20%) 
Musculoskeletal chest pain  1  3/59 (5.08%)  5/87 (5.75%) 
Myalgia  1  3/59 (5.08%)  2/87 (2.30%) 
Pain in extremity  1  4/59 (6.78%)  3/87 (3.45%) 
Nervous system disorders     
Dizziness  1  3/59 (5.08%)  5/87 (5.75%) 
Headache  1  11/59 (18.64%)  14/87 (16.09%) 
Psychiatric disorders     
Confusional state  1  7/59 (11.86%)  2/87 (2.30%) 
Insomnia  1  5/59 (8.47%)  8/87 (9.20%) 
Renal and urinary disorders     
Oliguria  1  3/59 (5.08%)  0/87 (0.00%) 
Renal impairment  1  3/59 (5.08%)  1/87 (1.15%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/59 (5.08%)  12/87 (13.79%) 
Dyspnoea  1  6/59 (10.17%)  7/87 (8.05%) 
Epistaxis  1  2/59 (3.39%)  5/87 (5.75%) 
Haemoptysis  1  3/59 (5.08%)  1/87 (1.15%) 
Oropharyngeal pain  1  4/59 (6.78%)  2/87 (2.30%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  2/59 (3.39%)  7/87 (8.05%) 
Vascular disorders     
Hypertension  1  3/59 (5.08%)  5/87 (5.75%) 
Hypotension  1  5/59 (8.47%)  5/87 (5.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 12.1
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.
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.
Publication. At least sixty (60) days prior to submitting or presenting a manuscript or other materials relating to the Study to a publisher, reviewer, or other outside persons, the Site shall provide to Sponsor a copy of all such manuscripts and materials , and allow Sponsor sixty (60) days to review and comment on them.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Vice President, Medical Head ID/IM/TX
Organization: Astellas Pharma Global Development, Inc.
Phone: (224) 205-8800
EMail: Astellas.resultsdisclosure@astellas.com
Layout table for additonal information
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 )
First Submitted: March 5, 2008
First Posted: March 12, 2008
Results First Submitted: December 2, 2015
Results First Posted: January 11, 2016
Last Update Posted: January 2, 2018