Clinical trial NCT00634049: Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Aspergillosis
Invasive Fungal Infections
Keywords: invasive fungal infections caused by rare molds, rare yeasts
BAL8557
Isavuconazole
Aspergillosis
or by dimorphic fungi
ASP9766
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica International Ltd
First posted: 2008-03-12
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Crude Success Rate of Overall Outcome of Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and End of Treatment (EOT).
timeFrame: Day 42, 84 and End of Treatment (EOT [Day 180])
Secondary outcomes:
measure: Crude Success Rate of Clinical Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
timeFrame: Day 42, 84 and End of Treatment (EOT [Day 180])
measure: Crude Success Rate of Mycological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
timeFrame: Day 42, 84 and End of Treatment (EOT [Day 180])
measure: Crude Success Rate of Radiological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
timeFrame: Day 42, 84 and End of Treatment (EOT [Day 180])
measure: Crude Success Rate of Clinical Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
timeFrame: Day 42, Day 84 and End of Treatment (EOT [Day 180])
measure: Crude Success Rate of Mycological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
timeFrame: Day 42, Day 84 and End of Treatment (EOT [Day 180])
measure: Crude Success Rate of Radiological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
timeFrame: Day 42, Day 84 and End of Treatment (EOT [Day 180])
measure: All-cause Mortality Through Day 42 and Day 84
timeFrame: Baseline to End of Treatment (EOT [Day 180])
measure: Safety - Overall Number of TEAEs
timeFrame: From the first study drug administration until 28 days after the last dose of study drug
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City Of Hope National Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Hospital
state: California
city: Aurora
country: United States
facility: University Of Colorado Health Sciences Center
state: Colorado
city: Atlanta
country: United States
facility: Emory Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago, Division of Infectious Diseases
state: Illinois
city: Beech Grove
country: United States
facility: Indiana BMT
state: Indiana
city: Indianapolis
country: United States
facility: Infectious Disease of Indiana
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Brigham & Womens Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Albany
country: United States
facility: Upstate Infectious Diseases Association LLP
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Lima
country: United States
facility: Regional Infection Diseases Infusion Center Inc.
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Health Sciences
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Health System
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center, Clinical Research
state: Washington
city: Ciudad Autonoma
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autonoma
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
city: Cordoba
country: Argentina
facility: Hospital Nuestra Senora de la Misericordia
city: Cordoba
country: Argentina
facility: Hospital San Roque
city: San Juan
country: Argentina
facility: Centro Polivalente de Asistencia e Investigación Clínica - CER San Juan
city: South Brisbane
country: Australia
facility: Mater Medical Centre
city: Woolloongabba
country: Australia
facility: Princess Alexandria Hospital
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: Erasme Hospital
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Belo Horizonte
country: Brazil
facility: Hospital Felicio Rocho
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
city: Curitiba
country: Brazil
facility: Hospital das Clinicas da UFPR
city: Ribeirao Preto
country: Brazil
facility: Hospital de Clinicas da FMUSP - Ribeirao Preto
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Clementino Fraga Filho
city: Santa Maria
country: Brazil
facility: Hospital Universitario de Santa Maria
city: São Paulo
country: Brazil
facility: Hospital Professor Edmundo Vasconcelos
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Henderson Site
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Montreal
country: Canada
facility: Hôpital Maisonneuve - Rosemont
state: Quebec
city: Montréal
country: Canada
facility: Hôpital Maisonneuve - Rosemont
state: Quebec
city: Santiago
country: Chile
facility: Hospital Clinico San Borja Arriaran
city: Alexandria
country: Egypt
facility: Alexandria University Hospital
city: Cairo
country: Egypt
facility: National Cancer Institute
city: Cairo
country: Egypt
facility: Nasser Institute
city: Lyon cedex 3
country: France
facility: Hôpital Edouard Herriot
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmette - Marseille
city: Nantes
country: France
facility: Hotel Dieu
city: Paris Cedex 10
country: France
facility: Hôpital Saint-Louis
city: Strasbourg Cedex
country: France
facility: Hopital Hautepierre
city: Vandoeuvre les Nancy
country: France
facility: Hôpital de Brabois Adultes
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen
city: Berlin
country: Germany
facility: Charite-Campus Benjamin Franklin
city: Köln
country: Germany
facility: Universitaet Koeln
city: Muenchen
country: Germany
facility: Klinikum Neuperlach
city: Würzburg
country: Germany
facility: Medizinische Klinik und Polyklinik II
city: Gurgaon
country: India
facility: Medanta Medicity Hospital
state: Haryan
city: Manipal
country: India
facility: Shirdi Sai Baba Cancer Hospital K. M. C. Hospital
state: Kama
city: Mumbai
country: India
facility: Tata Memorial Hopital, Department of Anesthesia
state: Mahara
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
state: Mahara
city: Chennai
country: India
facility: Global Hospitals & Health City
state: Tamilna
city: Ahmedabad
country: India
facility: Sterling Hospital
city: Hyderabad
country: India
facility: Apollo Hospitals
city: Pune
country: India
facility: Sahyadri Specialty Hospital
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Universtiy Hospital - Ein Kerem
city: Petah Tikva
country: Israel
facility: Rabin MC
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky MC Ichilov Hospital Tel Aviv
city: Buchon-si
country: Korea, Republic of
facility: Soonchunhyang University Bucheon Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Beirut
country: Lebanon
facility: Clinique Dr. Rizk
city: Beirut
country: Lebanon
facility: Rafik Hariri University Hospital
city: Guadalajara
country: Mexico
facility: Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: San Luis Potosi
country: Mexico
facility: Hospital Central Dr Ignacio Morones Prieto
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny
city: Moscow
country: Russian Federation
facility: S.I. Russian Oncological Research Center n.a. N.N. Blokhin
city: Moscow
country: Russian Federation
facility: State Institution "Hematology Research Center" RAMS
city: Petrozavodsk
country: Russian Federation
facility: Republican Hospital named after V.A. Baranov
city: St. Petersburg
country: Russian Federation
facility: St-Petersburg MA Postgraduate Education
city: Lyttleton
country: South Africa
facility: Private Practice
state: Gauteng
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital
city: Muang
country: Thailand
facility: Maharat Nakhon Ratchasima Hospital
city: Muang
country: Thailand
facility: Srinagarind Hospital
city: Muang
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Ratchathewi
country: Thailand
facility: Ramathibodi Hospital
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.