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

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

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.

Study Overview

• Status: Completed
• Conditions: Invasive Fungal Infections; Aspergillosis
• Intervention / Treatment: Drug: isavuconazole

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.

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: ASP9766; BAL8557

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Crude Success Rate of Clinical Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT	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.	Day 42, 84 and End of Treatment (EOT [Day 180])
Crude Success Rate of Mycological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT	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.	Day 42, 84 and End of Treatment (EOT [Day 180])
Crude Success Rate of Radiological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT	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.	Day 42, 84 and End of Treatment (EOT [Day 180])
Crude Success Rate of Clinical Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT	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.	Day 42, Day 84 and End of Treatment (EOT [Day 180])
Crude Success Rate of Mycological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT	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.	Day 42, Day 84 and End of Treatment (EOT [Day 180])
Crude Success Rate of Radiological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT	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.	Day 42, Day 84 and End of Treatment (EOT [Day 180])
All-cause Mortality Through Day 42 and Day 84	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.	Baseline to End of Treatment (EOT [Day 180])
Safety - Overall Number of TEAEs	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.	From the first study drug administration until 28 days after the last dose of study drug

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Collaborators: Basilea Pharmaceutica International Ltd

Publications and helpful links

General Publications

• Kovanda LL, Desai AV, Lu Q, Townsend RW, Akhtar S, Bonate P, Hope WW. Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study). Antimicrob Agents Chemother. 2016 Jul 22;60(8):4568-76. doi: 10.1128/AAC.00514-16. Print 2016 Aug.
• Thompson GR 3rd, Rendon A, Ribeiro Dos Santos R, Queiroz-Telles F, Ostrosky-Zeichner L, Azie N, Maher R, Lee M, Kovanda L, Engelhardt M, Vazquez JA, Cornely OA, Perfect JR. Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses. Clin Infect Dis. 2016 Aug 1;63(3):356-62. doi: 10.1093/cid/ciw305. Epub 2016 May 11.
• Marty FM, Ostrosky-Zeichner L, Cornely OA, Mullane KM, Perfect JR, Thompson GR 3rd, Alangaden GJ, Brown JM, Fredricks DN, Heinz WJ, Herbrecht R, Klimko N, Klyasova G, Maertens JA, Melinkeri SR, Oren I, Pappas PG, Racil Z, Rahav G, Santos R, Schwartz S, Vehreschild JJ, Young JH, Chetchotisakd P, Jaruratanasirikul S, Kanj SS, Engelhardt M, Kaufhold A, Ito M, Lee M, Sasse C, Maher RM, Zeiher B, Vehreschild MJGT; VITAL and FungiScope Mucormycosis Investigators. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016 Jul;16(7):828-837. doi: 10.1016/S1473-3099(16)00071-2. Epub 2016 Mar 9.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2008
• Primary Completion (Actual): January 3, 2014
• Study Completion (Actual): May 5, 2016

Study Registration Dates

• First Submitted: March 5, 2008
• First Submitted That Met QC Criteria: March 11, 2008
• First Posted (Estimate): March 12, 2008

Study Record Updates

• Last Update Posted (Actual): January 2, 2018
• Last Update Submitted That Met QC Criteria: December 7, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Isavuconazole; ASP9766; BAL8557; Aspergillosis; invasive fungal infections caused by rare molds, rare yeasts; or by dimorphic fungi
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Invasive Fungal Infections; Aspergillosis; Anti-Infective Agents; Antifungal Agents; Isavuconazole
• Other Study ID Numbers: 9766-CL-0103; WSA-CS-003 (Other Identifier: Basilea Protocol ID); 2006-005003-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Details of the IPD sharing plan for this study can be found at www.clinicalstudydatarequest.com.