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
  Purpose
The purpose of this study is to investigate the efficacy and safety of isavuconazole in the treatment of renally impaired participants with invasive fungal infections caused by Aspergillus and participants with invasive fungal disease caused by rare fungi.

Condition Intervention Phase
Aspergillosis
Invasive Fungal Infections
Drug: isavuconazole
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label Study of Isavuconazole in the Treatment of Participants With Aspergillosis and Renal Impairment or of Participants With Invasive Fungal Disease Caused by Rare Moulds, Yeasts or Dimorphic Fungi

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • 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]) ] [ Designated as safety issue: No ]

    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.



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

    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.


  • 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]) ] [ Designated as safety issue: No ]

    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.


  • 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]) ] [ Designated as safety issue: No ]

    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.


  • 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]) ] [ Designated as safety issue: No ]

    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.


  • 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]) ] [ Designated as safety issue: No ]

    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.


  • 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]) ] [ Designated as safety issue: No ]

    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.


  • All-cause Mortality Through Day 42 and Day 84 [ Time Frame: Baseline to End of Treatment (EOT [Day 180]) ] [ Designated as safety issue: No ]

    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.


  • Safety - Overall Number of TEAEs [ Time Frame: From the first study drug administration until 28 days after the last dose of study drug ] [ Designated as safety issue: No ]
    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.


Enrollment: 149
Study Start Date: April 2008
Study Completion Date: May 2016
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Isavuconazole
Administration of isavuconazole 3 times a day in the vein (IV) or oral as a capsule for 2 days followed by daily administration of isavuconazole (IV) or oral
Drug: isavuconazole
Administration of 200 mg isavuconazole 3 times a day in the vein (IV) or oral as a capsule for 2 days, followed by daily administration of 200 mg isavuconazole (IV) or oral
Other Names:
  • BAL8557
  • ASP9766

Detailed Description:
Acute invasive fungal infections caused by aspergillus, rare moulds, yeasts or dimorphic fungi are life threatening diseases. Early treatment with highly effective anti-fungals reduces mortality. This study investigates the safety and efficacy of isavuconazole in participants with aspergillosis and renal impairment, and in participants suffering from invasive infections from rare fungi.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

•Participants meeting EORTC/MSG (European Organization for the Research and Treatment of Cancer/Mycoses Study Group) definition of proven or culture positive probable IFD (invasive fungal disease) caused by rare moulds, yeasts, or dimorphic fungi (i.e. fungal pathogens other than Aspergillus fumigatus or Candida species) whether renally impaired or not (including dialysis) who require primary therapy for their IFD at the time of enrollment.

OR

•Participants who had proven or probable zygomycosis, whether renally impaired or not (including dialysis), who require primary therapy. Zygomycosis must be documented by culture or histology / cytology.

OR

•Participants meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare moulds, yeasts, or dimorphic fungi (i.e., fungal pathogens other than Aspergillus fumigatus or Candida species), whether RI or not (including dialysis), who were refractory to current treatment defined as,

  • Clear documentation of progression of disease. Note: radiological progression only in association with white blood cell (WBC) count recovery was not acceptable.
  • Failure to improve clinically despite receiving at least 7 days of standard antifungal regimen. Prior to enrolling patients who fell into this category, the Medical Monitor was contacted for approval.

OR

• Participants meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare moulds, yeasts, or dimorphic fungi (i.e., fungal pathogens other than Aspergillus fumigatus or Candida species), whether RI or not (including dialysis), who were intolerant to current treatment for example:

  • Doubling of serum creatinine value to higher than the upper limit of normal (ULN) within 48 hours.
  • Serum creatinine > 2.0 mg/mL and current treatment with polyene or IV voriconazole.
  • Other significant drug-related adverse reaction(s) to the current antifungal agent, resulting in discontinuation of the treatment, e.g., persistence of visual disturbance, allergic reaction, phototoxicity or severe infusion reaction (hypertensive crisis, severe chills or shock).
  • Documented inability to achieve adequate blood levels of posaconazole, voriconazole or itraconazole.

Exclusion Criteria:

  • A known condition of the participants that may jeopardize adherence to the protocol requirements
  • Participants who are unlikely to survive 30 days
  • Participants with a body weight < 40 kg
  • Women who are pregnant or breastfeeding
  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: NCT00634049

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
City Of Hope National Medical Center
Duarte, California, United States, 91010
University of California Davis Health System
Sacramento, California, United States, 95817
University of California at San Francisco
San Francisco, California, United States, 94143
California Pacific Medical Center
San Francisco, California, United States, 94110
Stanford University Hospital
Stanford, California, United States, 94303
United States, Colorado
University Of Colorado Health Sciences Center
Aurora, Colorado, United States, 80045
United States, Georgia
Emory Hospital
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago, Division of Infectious Diseases
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana BMT
Beech Grove, Indiana, United States, 46107
Infectious Disease of Indiana
Indianapolis, Indiana, United States, 46280
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Massachusetts
Brigham & Womens Hospital
Boston, Massachusetts, United States, 02115
UMASS Memorial Medical Center
Worcester, Massachusetts, United States, 01655
United States, Michigan
Wayne State University School of Medicine
Detroit, Michigan, United States, 48201
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Upstate Infectious Diseases Association LLP
Albany, New York, United States, 12208
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Regional Infection Diseases Infusion Center Inc.
Lima, Ohio, United States, 45801
United States, Pennsylvania
Temple University Health Sciences
Philadelphia, Pennsylvania, United States, 19140
University of Pittsburgh Medical Center Health System
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center, Clinical Research
Seattle, Washington, United States, 98109
Argentina
Hospital Italiano de Buenos Aires
Ciudad Autonoma, Argentina, 1181
Instituto Medico Especializado Alexander Fleming
Ciudad Autonoma, Argentina, 1426
Hospital Nuestra Senora de la Misericordia
Cordoba, Argentina, 5000
Hospital San Roque
Cordoba, Argentina, 5000
Centro Polivalente de Asistencia e Investigación Clínica - CER San Juan
San Juan, Argentina, 5402
Australia
Mater Medical Centre
South Brisbane, Australia, 4101
Princess Alexandria Hospital
Woolloongabba, Australia, 4102
Belgium
Institut Jules Bordet
Brussels, Belgium, 1000
Erasme Hospital
Bruxelles, Belgium, 1070
Universitair Ziekenhuis Gent
Gent, Belgium, 9000
Universitaire Ziekenhuizen Leuven
Leuven, Belgium, 3000
Brazil
Hospital Felicio Rocho
Belo Horizonte, Brazil, 30110-908
Santa Casa de Misericordia de Belo Horizonte
Belo Horizonte, Brazil, 30150-221
Hospital das Clinicas da UFPR
Curitiba, Brazil, 80060-150
Hospital de Clinicas da FMUSP - Ribeirao Preto
Ribeirao Preto, Brazil, 14048-900
Hospital Universitario Clementino Fraga Filho
Rio de Janeiro, Brazil, 21941-913
Hospital Universitario de Santa Maria
Santa Maria, Brazil, 97105-900
Hospital Professor Edmundo Vasconcelos
São Paulo, Brazil, 04038-905
Canada, Ontario
Hamilton Health Sciences - Henderson Site
Hamilton, Ontario, Canada, L8V 1C3
The Ottawa Hospital - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Canada, Quebec
Hôpital Maisonneuve - Rosemont
Montreal, Quebec, Canada, H1T 2M4
Hôpital Maisonneuve - Rosemont
Montréal, Quebec, Canada, H1T 2M4
Chile
Hospital Clinico San Borja Arriaran
Santiago, Chile, 8320000
Egypt
Alexandria University Hospital
Alexandria, Egypt, 21131
National Cancer Institute
Cairo, Egypt, 11796
Nasser Institute
Cairo, Egypt, 12655
France
Hôpital Edouard Herriot
Lyon cedex 3, France, 69437
Institut Paoli Calmette - Marseille
Marseille Cedex 9, France, 13273
Hotel Dieu
Nantes, France, 44093
Hôpital Saint-Louis
Paris Cedex 10, France, 75475
Hopital Hautepierre
Strasbourg Cedex, France, 67048
Hôpital de Brabois Adultes
Vandoeuvre les Nancy, France, 54511
Germany
Universitaetsklinikum Aachen
Aachen, Germany, 52074
Charite-Campus Benjamin Franklin
Berlin, Germany, 12200
Universitaet Koeln
Köln, Germany, 50931
Klinikum Neuperlach
Muenchen, Germany, 81737
Medizinische Klinik und Polyklinik II
Würzburg, Germany, 97080
India
Medanta Medicity Hospital
Gurgaon, Haryan, India, 122001
Shirdi Sai Baba Cancer Hospital K. M. C. Hospital
Manipal, Kama, India, 576104
Tata Memorial Hopital, Department of Anesthesia
Mumbai, Mahara, India, 400012
Deenanath Mangeshkar Hospital & Research Centre
Pune, Mahara, India, 411004
Global Hospitals & Health City
Chennai, Tamilna, India, 600100
Sterling Hospital
Ahmedabad, India, 380052
Apollo Hospitals
Hyderabad, India, 500033
Sahyadri Specialty Hospital
Pune, India, 411004
Israel
Rambam Health Care Campus
Haifa, Israel, 31096
Hadassah Universtiy Hospital - Ein Kerem
Jerusalem, Israel, 91200
Rabin MC
Petah Tikva, Israel, 49100
Chaim Sheba Medical Center
Ramat-Gan, Israel, 52621
Sourasky MC Ichilov Hospital Tel Aviv
Tel Aviv, Israel, 64239
Korea, Republic of
Soonchunhyang University Bucheon Hospital
Buchon-si, Korea, Republic of, 420-767
Gachon University Gil Hospital
Incheon, Korea, Republic of, 405-760
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
The Catholic University of Korea
Seoul, Korea, Republic of, 137-701
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Lebanon
American University of Beirut Medical Center
Beirut, Lebanon, 11-0236
Clinique Dr. Rizk
Beirut, Lebanon, 1107-2130
Rafik Hariri University Hospital
Beirut, Lebanon, 5244
Mexico
Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
Guadalajara, Mexico, 44280
Instituto Nacional de Ciencias Medicas y Nutricion Salvador
Mexico City, Mexico, 14000
Hospital Universitario Dr Jose Eleuterio Gonzalez
Monterrey, Mexico, 64460
Hospital Central Dr Ignacio Morones Prieto
San Luis Potosi, Mexico, 78240
Poland
Samodzielny Publiczny Centralny Szpital Kliniczny
Warszawa, Poland, 02097
Russian Federation
State Institution "Hematology Research Center" RAMS
Moscow, Russian Federation, 125167
S.I. Russian Oncological Research Center n.a. N.N. Blokhin
Moscow, Russian Federation, 115478
Republican Hospital named after V.A. Baranov
Petrozavodsk, Russian Federation, 185019
St-Petersburg MA Postgraduate Education
St. Petersburg, Russian Federation, 194291
South Africa
Private Practice
Lyttleton, Gauteng, South Africa, 0157
Thailand
Songklanagarind Hospital
Hat Yai, Thailand, 90110
Maharaj Nakorn Chiang Mai Hospital
Muang, Thailand, 50200
Srinagarind Hospital
Muang, Thailand, 40002
Maharat Nakhon Ratchasima Hospital
Muang, Thailand, 30000
Ramathibodi Hospital
Ratchathewi, Thailand, 10400
Sponsors and Collaborators
Astellas Pharma Inc
Basilea Pharmaceutica International Ltd
  More Information

Additional Information:
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00634049     History of Changes
Other Study ID Numbers: 9766-CL-0103  WSA-CS-003  2006-005003-33 
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)

Keywords provided by Astellas Pharma Inc:
invasive fungal infections caused by rare molds, rare yeasts
BAL8557
Isavuconazole
Aspergillosis
or by dimorphic fungi
ASP9766

Additional relevant MeSH terms:
Mycoses
Aspergillosis
Hyalohyphomycosis
Dermatomycoses
Skin Diseases, Infectious
Infection
Skin Diseases

ClinicalTrials.gov processed this record on July 26, 2016