Isavuconazole (BAL8557) for Primary Treatment of Invasive Aspergillosis

Phase 3

Completed

Conditions: Aspergillosis
Invasive Fungal Infection

Interventions: Drug: Isavuconazole
Drug: Voriconazole

Registration Number: NCT00412893

Lead Sponsor: Astellas Pharma Inc

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 527

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Isavuconazole	Isavuconazole	Participants received a loading dose of isavuconazole, 200 mg three times a day by intravenous infusion (IV) for the first 2 days followed by a maintenance dose from Day 3 of 200 mg once daily either IV or orally until they reached a treatment endpoint or for a maximum of 84 days.
Voriconazole	Voriconazole	Participants received a loading dose of voriconazole, 6 mg/kg every 12 hours IV for the first 24 hours, followed by a maintenance dose of 4 mg/kg every 12 hours by IV on Day 2. Beginning on Day 3, participants received 4 mg/kg every 12 hours by IV or 200 mg every 12 hours orally, until they reached a treatment endpoint or for a maximum of 84 days.

Primary Outcome Measures

Name	Time	Method
All-cause Mortality Through Day 42	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With an Overall Outcome of Success Evaluated by the Data Review Committee (DRC)	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.	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.
All-cause Mortality Through Day 84	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.
Percentage of Participants With an Overall Outcome of Success Evaluated by Investigator	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.	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).
Percentage of Participants With a Clinical Response Assessed by the DRC	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.	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.
Percentage of Participants With a Mycological Response Assessed by the DRC	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.	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.
Percentage of Participants With a Radiological Response Assessed by the DRC	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.	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.
Percentage of Participants With a Clinical Response Assessed by the Investigator	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.	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.
Percentage of Participants With a Mycological Response Assessed by the Investigator	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.	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.
Percentage of Participants With a Radiological Response Assessed by the Investigator	Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.	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.
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.

Trial Locations

Locations (81): Hospital Italiano de Buenos Aires
🇦🇷
Ciudad Autonoma, Argentina
University of Alabama
🇺🇸
Birmingham, Alabama, United States
University of Chicago, Division of Infectious Diseases
🇺🇸
Chicago, Illinois, United States
AZ ST Jan
🇧🇪
Brugge, Belgium
University of California at San Francisco
🇺🇸
San Francisco, California, United States
Infectious Disease of Indiana
🇺🇸
Indianapolis, Indiana, United States
Petz Aladar Megyei Oktato Korhaz
🇭🇺
Györ, Hungary
Alexandria University Hospital
🇪🇬
Alexandria, Egypt
CHU de Nantes - Hôpital Hôtel Dieu
🇫🇷
Nantes Cedex, France
Regional Infection Diseases Infusion Center Inc.
🇺🇸
Lima, Ohio, United States
Upstate Infectious Diseases Association LLP
🇺🇸
Albany, New York, United States
Springfield Clinic LLP
🇺🇸
Springfield, Illinois, United States
National Cancer Institute
🇪🇬
Cairo, Egypt
Srinagarind Hospital
🇹🇭
Muang, Thailand
St-Petersburg MA Postgraduate Education
🇷🇺
St. Petersburg, Russian Federation
Maharaj Nakorn Chiang Mai Hospital
🇹🇭
Muang, Thailand
Universitaet Koeln
🇩🇪
Köln, Germany
Songklanagarind Hospital
🇹🇭
Hat Yai, Thailand
Maharat Nakhon Ratchasima Hospital
🇹🇭
Muang, Thailand
Tata Memorial Hopital, Department of Anesthesia
🇮🇳
Mumbai, Mahara, India
The Affiliated Union Hospital of Fujian Medical University
🇨🇳
Fuzhou, China
The First Affiliated Hospital, Med. School, Zhejiang Uni.
🇨🇳
Hangzhou, China
The 1st Affiliated Hospital of Guangxi Medical University
🇨🇳
Nanning, China
Huashan Hospital, Insitute of Antibiotics
🇨🇳
Shanghai, China
No.6 Renmin Hosp. of Shanghai City
🇨🇳
Shanghai, China
Chang Hai Hospital
🇨🇳
Shanghai, China
Wuhan Union Hospital
🇨🇳
Wuhan, China
Unità Funzionale di Ematologia; Azienda Ospedaliera Universitaria Careggi
🇮🇹
Firenze, Italy
Chaim Sheba Medical Center
🇮🇱
Ramat-Gan, Israel
Rabin MC
🇮🇱
Petah Tikva, Israel
Indiana BMT
🇺🇸
Springfield, Illinois, United States
Instituto Medico Especializado Alexander Fleming
🇦🇷
Ciudad Autonoma, Argentina
Brigham & Womens Hospital
🇺🇸
Boston, Massachusetts, United States
Mater Medical Centre
🇦🇺
South Brisbane, Australia
Felicio Rocho
🇧🇷
Belo Horizonte, Brazil
Universitaire Ziekenhuizen Leuven
🇧🇪
Leuven, Belgium
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, Brazil
Hamilton Health Sciences - Henderson Site
🇨🇦
Hamilton, Canada
Hospital Dr. Hernan Henriquez Aravena
🇨🇱
Temuco, Chile
The 1st Hospital, Jilin University
🇨🇳
Changchun, China
The Third Xiangya Hospital of Central South University
🇨🇳
Changsha, China
The Ottawa Hospital - General Campus
🇨🇦
Ottawa, Ontario, Canada
3rd Hospital, Peking University
🇨🇳
Beijing, China
West China Hospital of Sichuan University
🇨🇳
Chengdu, China
Nasser Institute
🇪🇬
Cairo, Egypt
Hotel Dieu
🇫🇷
Nantes Cedex 01, France
Universitaetsklinikum Aachen
🇩🇪
Aachen, Germany
Charité Universitaetsmedizin Berlin- Campus Charité Mitte
🇩🇪
Berlin, Germany
Szegedi Tudomanyegyetem
🇭🇺
Szeged, Hungary
Klinikum Schwabing
🇩🇪
Muenchen, Germany
Kasturba Medical College and Hospital
🇮🇳
Mangalore, Karna, India
Hadassah Universtiy Hospital - Ein Kerem
🇮🇱
Jerusalem, Israel
Rambam Health Care Campus
🇮🇱
Haifa, Israel
Sourasky MC Ichilov Hospital Tel Aviv
🇮🇱
Tel Aviv, Israel
Gachon University Gil Hospital
🇰🇷
Incheon, Korea, Republic of
Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽
Monterrey, Mexico
Azienda Ospedaliera Ospedale Niguarda Ca' Granda
🇮🇹
Milano, Italy
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
The Catholic University of Korea, St. Mary's Hospital
🇰🇷
Seoul, Korea, Republic of
Samodzielny Publiczny Centralny Szpital Kliniczny
🇵🇱
Warszawa, Poland
Leningrad Regional Hospital
🇷🇺
St. Petersburg, Russian Federation
State Institution "Hematology Research Center" RAMS
🇷🇺
Moscow, Russian Federation
Republican Hospital named after V.A. Baranov
🇷🇺
Petrozavodsk, Russian Federation
Medizinische klinik und Polyklinik II
🇩🇪
Würzburg, Germany
Universitaetsklinik Leipzig
🇩🇪
Leipzig, Germany
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Hôpital Hautepierre
🇫🇷
Strasbourg, France
Hôpital de brabois adultes
🇫🇷
Vandoeuvre les Nancy, France
Sahyadri Hospital
🇮🇳
Pune, Mahara, India
Sterling Hospital
🇮🇳
Ahmedabad, Gujarat, India
Shirdi Sai Baba Cancer Hospital K. M. C. Hospital
🇮🇳
Manipal, Karna, India
Deenanath Mangeshkar Hospital & Research Centre
🇮🇳
Pune, Mahara, India
ULB Hospital Erasme
🇧🇪
Bruxelles, Belgium
Universitair Ziekenhuis Gent
🇧🇪
Gent, Belgium
Apollo Hospitals
🇮🇳
Hyderabad, Andh Prad, India
Institut Jules Bordet
🇧🇪
Brussels, Belgium
The First Affiliated Hospital of Nanjing Medical University
🇨🇳
Nanjing, China