Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi

Aspergillosis Clinical Trial

— VITAL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00634049
• Other study ID #: 9766-CL-0103
• Secondary ID: WSA-CS-0032006-0
• Status: Completed
• Phase: Phase 3
• First received: March 5, 2008
• Last updated: December 7, 2017
• Start date: April 22, 2008
• Est. completion date: May 5, 2016

Study information

• Verified date: December 2017
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 149
• Est. completion date: May 5, 2016
• Est. primary completion date: January 3, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aspergillosis
• Invasive Fungal Infections
• Mycoses

Intervention

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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Inc	Basilea Pharmaceutica International Ltd

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  Egypt,  France,  Germany,  India,  Israel,  Korea, Republic of,  Lebanon,  Mexico,  Poland,  Russian Federation,  South Africa,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Crude Success Rate of Overall Outcome of Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and End of Treatment (EOT).	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	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])
Secondary	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])
Secondary	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])
Secondary	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])
Secondary	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])
Secondary	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])
Secondary	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])
Secondary	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

External Links

•   Link to results on Astellas Clinical Study Results website