Isavuconazole (BAL8557) for Primary Treatment of Invasive Aspergillosis

Aspergillosis Clinical Trial

Official title:

A Phase III, Double Blind, Randomized Study to Evaluate Safety and Efficacy of BAL8557 Versus Voriconazole for Primary Treatment of Invasive Fungal Disease Caused by Aspergillus Species or Other Filamentous Fungi.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00412893
• Other study ID #: 9766-CL-0104
• Secondary ID: WSA-CS-0042006-0
• Status: Completed
• Phase: Phase 3
• Start date: March 7, 2007
• Est. completion date: March 28, 2013

Study information

• Verified date: March 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy and safety of isavuconazole versus voriconazole in the treatment of patients with invasive aspergillosis.

Description:

Acute invasive fungal infections caused by aspergillus, zygomycetes and other filamentous fungi remain life threatening diseases. Early treatment with highly effective anti-fungals reduces mortality. This study investigates the efficacy and safety of isavuconazole in the treatment of invasive fungal diseases, caused by Aspergillus or other filamentous fungi.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 527
• Est. completion date: March 28, 2013
• Est. primary completion date: March 28, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have proven, probable or possible invasive fungal disease caused by Aspergillus species or other filamentous fungi

• Female patients must be non-lactating and at no risk for pregnancy

Exclusion Criteria:

• Patients with invasive fungal infections other than Aspergillus species or other filamentous fungi

• Evidence of hepatic dysfunction at Baseline or moderate to severe renal dysfunction

• Patients with chronic aspergillosis, or aspergilloma or allergic bronchopulmonary aspergillosis

• Patients who have received more than 4 days of systemic antifungal therapy other than fluconazole within the 7 days prior to the first administration of study medication

• Patients previously enrolled in a Phase III study with isavuconazole

• Patients with a body weight </= 40 kg

Related Conditions & MeSH terms

• Aspergillosis
• Invasive Fungal Infection
• Invasive Fungal Infections
• Mycoses

Intervention

Drug:
• Isavuconazole
Loading doses were administered as IV infusion and maintenance doses were administered as IV infusion or oral (capsules).
• Voriconazole
Loading doses were administered as IV infusion and maintenance doses were administered as IV infusion or oral (capsules).

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma
Argentina	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma
Australia	Mater Medical Centre	South Brisbane
Belgium	AZ ST Jan	Brugge
Belgium	Institut Jules Bordet	Brussels
Belgium	ULB Hospital Erasme	Bruxelles
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Brazil	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	Ribeirão Preto
Brazil	Hospital Universitario Clementino Fraga Filho	Rio de Janeiro
Canada	Hamilton Health Sciences - Henderson Site	Hamilton
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Chile	Hospital Dr. Hernan Henriquez Aravena	Temuco
China	3rd Hospital, Peking University	Beijing
China	The 1st Hospital, Jilin University	Changchun
China	The Third Xiangya Hospital of Central South University	Changsha
China	West China Hospital of Sichuan University	Chengdu
China	The Affiliated Union Hospital of Fujian Medical University	Fuzhou
China	The First Affiliated Hospital, Med. School, Zhejiang Uni.	Hangzhou
China	The First Affiliated Hospital of Nanjing Medical University	Nanjing
China	The 1st Affiliated Hospital of Guangxi Medical University	Nanning
China	Chang Hai Hospital	Shanghai
China	Huashan Hospital, Insitute of Antibiotics	Shanghai
China	No.6 Renmin Hosp. of Shanghai City	Shanghai
China	Wuhan Union Hospital	Wuhan
Egypt	Alexandria University Hospital	Alexandria
Egypt	Nasser Institute	Cairo
Egypt	National Cancer Institute	Cairo
France	CHU de Nantes - Hôpital Hôtel Dieu	Nantes Cedex
France	Hotel Dieu	Nantes Cedex 01
France	Hôpital Hautepierre	Strasbourg
France	Hôpital de brabois adultes	Vandoeuvre les Nancy
Germany	Universitaetsklinikum Aachen	Aachen
Germany	Charité Universitaetsmedizin Berlin- Campus Charité Mitte	Berlin
Germany	Universitaet Koeln	Köln
Germany	Universitaetsklinik Leipzig	Leipzig
Germany	Klinikum Schwabing	Muenchen
Germany	Medizinische klinik und Polyklinik II	Würzburg
Hungary	Petz Aladar Megyei Oktato Korhaz	Györ
Hungary	Szegedi Tudomanyegyetem	Szeged
India	Sterling Hospital	Ahmedabad	Gujarat
India	Apollo Hospitals	Hyderabad	Andh Prad
India	Kasturba Medical College and Hospital	Mangalore	Karna
India	Shirdi Sai Baba Cancer Hospital K. M. C. Hospital	Manipal	Karna
India	Tata Memorial Hopital, Department of Anesthesia	Mumbai	Mahara
India	Deenanath Mangeshkar Hospital & Research Centre	Pune	Mahara
India	Sahyadri Hospital	Pune	Mahara
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
Italy	Unità Funzionale di Ematologia; Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Azienda Ospedaliera Ospedale Niguarda Ca' Granda	Milano
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, St. Mary's Hospital	Seoul
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Monterrey
Poland	Samodzielny Publiczny Centralny Szpital Kliniczny	Warszawa
Russian Federation	State Institution "Hematology Research Center" RAMS	Moscow
Russian Federation	Republican Hospital named after V.A. Baranov	Petrozavodsk
Russian Federation	Leningrad Regional Hospital	St. Petersburg
Russian Federation	St-Petersburg MA Postgraduate Education	St. Petersburg
Thailand	Songklanagarind Hospital	Hat Yai
Thailand	Maharaj Nakorn Chiang Mai Hospital	Muang
Thailand	Maharat Nakhon Ratchasima Hospital	Muang
Thailand	Srinagarind Hospital	Muang
United States	Upstate Infectious Diseases Association LLP	Albany	New York
United States	University of Alabama	Birmingham	Alabama
United States	Brigham & Womens Hospital	Boston	Massachusetts
United States	University of Chicago, Division of Infectious Diseases	Chicago	Illinois
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 California at San Francisco	San Francisco	California
United States	Indiana BMT	Springfield	Illinois
United States	Springfield Clinic LLP	Springfield	Illinois

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,  China,  Egypt,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Poland,  Russian Federation,  Spain,  Switzerland,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause Mortality Through Day 42	All-cause mortality is represented as the percentage of participants who died after first dose of study drug through Day 42 from any cause. Participants with unknown survival status through Day 42 were included as deaths in the calculation.	Through Day 42
Secondary	Percentage of Participants With an Overall Outcome of Success Evaluated by the Data Review Committee (DRC)	The DRC was an independent, blinded committee consisting of experts in the field of infectious disease who assessed patients' outcomes. The overall response was based on the DRC-assessed clinical, mycological and radiological responses.; Success was defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings, the eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline and a > 50% improvement in radiological response from Baseline (or improvement of at least 25% from Baseline for the Day 42 analysis or End of Treatment if it occurred prior to Day 42).; End of treatment (EOT) is the last day of study drug administration. For the Day 42 and Day 84 analyses, any visits that the DRC assessed as Not Done were considered a failure for that visit. A death before Day 42 was also considered a failure, even if the DRC assessed the participant to be a success prior to death.	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary	All-cause Mortality Through Day 84	All-cause mortality is represented as the percentage of participants who died after first dose of study drug through Day 84 from any cause. Participants with unknown survival status through Day 84 were included as deaths in the calculation.	Through Day 84
Secondary	Percentage of Participants With an Overall Outcome of Success Evaluated by Investigator	Overall response based on investigators' assessments was not derived as it was not deemed necessary because participants overall response status was determined by the DRC. All investigators' assessments of clinical, mycological and radiological responses are analyzed separately (see Outcome Measures 8-10).	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary	Percentage of Participants With a Clinical Response Assessed by the DRC	Blinded assessments of clinical symptoms and physical findings of invasive fungal disease were performed by the independent DRC.; Clinical response is defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings. Failure is defined as no resolution of any attributable clinical symptoms and physical findings and/or worsening. Participants with no attributable signs and symptoms present at Baseline and no symptoms attributable to invasive fungal disease (IFD) developed post-baseline were classified as "Not Applicable." End of treatment is the last day of study drug administration.	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary	Percentage of Participants With a Mycological Response Assessed by the DRC	Blinded mycological assessments of the participant's invasive fungal disease status were performed by the independent DRC using the results from fungal culture and isolation and/or histology/cytology of biopsy or biological fluid samples from the infected site.; Mycological response is defined as eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline. Failure was defined as persistence or presumed persistence. Participants with no mycological evidence available at Baseline were classified as "Not Applicable".; End of treatment is the last day of study drug administration.	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary	Percentage of Participants With a Radiological Response Assessed by the DRC	Independent reviews of radiology assessments were completed by radiology experts which were provided to the independent, blinded DRC. Blinded radiological assessments were performed by the DRC.; Radiological response is defined as a = 50% improvement from Baseline, or improvement of at least 25% from Baseline for the Day 42 analysis or if end of treatment occurred before Day 42. Participants without any radiology at Baseline were considered "Not Applicable." End of Treatment is the last day of study drug administration.	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary	Percentage of Participants With a Clinical Response Assessed by the Investigator	Assessment of clinical symptoms and physical findings of invasive fungal disease were performed by the investigator.; Clinical response is defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings. Failure is defined as no resolution of any attributable clinical symptoms and physical findings and/or worsening, or if results were unavailable or the participant was unevaluable. Participants with no attributable signs and symptoms present at Baseline were classified as "Not Applicable." End of treatment is the last day of study drug administration.	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary	Percentage of Participants With a Mycological Response Assessed by the Investigator	Mycological assessments of the participant's invasive fungal disease status were performed by the investigator using the results from fungal culture and isolation and/or histology/cytology of biopsy or biological fluid samples from the infected site.; Mycological response is defined as eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline. Failure was defined as persistence or presumed persistence. Participants with no mycological evidence available at Baseline, or no mycological follow-up results available or indeterminate results were classified as "Not Applicable".; End of treatment is the last day of study drug administration.	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary	Percentage of Participants With a Radiological Response Assessed by the Investigator	Radiological assessments were performed by the investigator. Radiological response is defined as a = 50% improvement from Baseline, or improvement of at least 25% from Baseline for the Day 42 analysis or if end of treatment occurred before Day 42. Failure is defined as a < 25% improvement at any time or results not available. Participants with no signs on radiological images at Baseline were considered "Not Applicable." End of Treatment is the last day of study drug administration.	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary	Number of Participants With Adverse Events, Reported by System Organ Class		From the first study drug administration until 28 days after the last dose of study drug. The median duration of study drug administration was 45 days.

External Links

•   Link to results on Astellas Clinical Study Results website