Isavuconazole (BAL8557) in the Treatment of Candidemia and Other Invasive Candida Infections

Mycoses Clinical Trial

Official title:

A Phase III, Double-blind, Randomized Study to Evaluate the Safety and Efficacy of BAL8557 Versus a Caspofungin Followed by Voriconazole Regimen in the Treatment of Candidemia and Other Invasive Candida Infections

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00413218
• Other study ID #: 9766-CL-0105
• Secondary ID: WSA-CS-0082006-0
• Status: Completed
• Phase: Phase 3
• Start date: March 8, 2007
• Est. completion date: March 3, 2015

Study information

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

Clinical Trial Summary

The purpose of the study is to compare the safety and efficacy of isavuconazole versus caspofungin followed by voriconazole in the treatment of candidemia and other invasive Candida infections.

Description:

Candida infections, representing approximately 80% of all major systemic fungal infections, are the fourth most common cause of nosocomial bloodstream infections, with a mortality rate of 40%. Isavuconazole is not yet approved for the treatment of fungal infections. This study investigates the efficacy and safety of intravenous and oral isavuconazole. Patients are randomized to isavuconazole and the reference regimen. Patients with a positive blood- or deep tissue culture of candida fungi can be included.

Other known NCT identifiers

• NCT00444366

Recruitment information / eligibility

• Status: Completed
• Enrollment: 450
• Est. completion date: March 3, 2015
• Est. primary completion date: March 3, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with candidemia or with an invasive Candida infection

• Presence of fever, hypothermia or other appropriate local sign of infection

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

Exclusion Criteria:

• Patients with a sole diagnosis of mucocutaneous candidiasis, i.e. oropharyngeal, esophageal or genital candidiasis; or candidal lower urinary tract infection or Candida isolated solely from respiratory tract specimens

• Patients with candidemia who failed a previous antifungal therapy for the same infection

• Patients previously enrolled in a phase III study with isavuconazole

• Patients with a body weight <40kg

Related Conditions & MeSH terms

• Candidemia
• Candidiasis
• Candidiasis, Invasive
• Infection
• Mycoses

Intervention

Drug:
• Isavuconazole
Administered by intravenous infusion.
• Caspofungin
Administered by intravenous infusion.
• Voriconazole
Administered by intravenous infusion.

Locations

Country	Name	City	State
Argentina	Hospital Britanico de Buenos Aires	Capital Federal
Argentina	Hospital General de Agudos Dr. Carlos G. Durand	Capital Federal
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma
Argentina	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma
Argentina	Hospital General de Agudos Dr. Cosme Argerich	La Boca
Australia	Fremantle Hospital	Fremantle
Australia	Mater Adult Hospital	South Brisbane
Australia	Westmead Hospital	Westmead
Australia	Princess Alexandra Hospital	Woolloongabba
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Brussel	Brussels
Belgium	ULB Hôpital Erasme	Bruxelles
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Brazil	Hospital das Clinicas da Universidade Federal de Minas Gerai	Belo Horizonte
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 Nossa Senhora das Gracas	Curitiba
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Hospital Universitario Clementino Fraga Filho	Rio de Janeiro
Brazil	Hospital Universitario de Santa Maria	Santa Maria
Brazil	Universidade Federal de Sao Paulo - UNIFESP	São Paulo
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Hamilton Health Sciences - Henderson Site	Hamilton	Ontario
Canada	Queen's University	Kingston	Ontario
Canada	Hôpital Maisonneuve - Rosemont	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	University Health Network - Toronto General Hospital	Toronto	Ontario
Chile	Hospital Dr. Sotero del Rio	Puente Alto Santiago
Chile	Hospital del Salvador	Santiago
Chile	Hospital Dr. Hernan Henriquez Aravena	Temuco
China	West China Hospital of Sichuan University	Chengdu
China	Huashan Hospital Fudan University	Shanghai
France	Hôpital Hautepierre	Strasbourg
France	Hôpital de Brabois Adultes	Vandoeuvre les Nancy
Germany	Charite Campus Mitte	Berlin
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Universitaet Koeln	Koeln
Germany	Klinikum St. Georg	Leipzig
Germany	Universitaetsklinik Leipzig	Leipzig
Germany	Universitaetsklinikum Leipzig	Luebeck
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Hungary	Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz	Györ
India	Apollo Hospitals Educational & Research Foundation	Chennai
India	Amrita Institute Of Medical Science	Cochin	Kerala
India	Nizam's Institute of Medical Sciences	Hyderabad
India	AMRI Hospital	Kolkata
India	Kasturba Medical College and Hospital	Mangalore	Karna
India	Kasturba Medical College K. M. C. Hospital	Manipal	Karna
India	Max Super Speciality Hospital	New Delhi	Delhi
India	Metro Centre for Respiratory Diseases	Noida	Delhi
India	Deenanath Mangeshkar Hospital and Research Centre	Pune	Mahara
India	Christian Medical College & Hospital	Vellore Tamilnadu
Israel	Ha Emek Medical Center	Afula
Israel	Rambam Health Care Campus	Haifa
Israel	Wolfson Medical Center	Holon
Israel	Hadassah Universtiy Hospital - Ein Kerem	Jerusalem
Israel	Sapir Medical Center, Meir Hospital	Kfar-Saba
Israel	Rabin MC	Petah
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Sourasky MC Ichilov Hospital Tel Aviv	Tel Aviv
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Ma	Bologna
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedaliero Universitaria San Martino	Genova
Italy	Ente Ospedaliero Ospedeli Galliera	Genova
Italy	Azienda Ospedaliera di Verona-Ospedale Civile Maggiore	Verona
Lebanon	AUB Medical Center	Beirut
Lebanon	Rafik Hariri Uni Hospital	Beirut
Malaysia	Hospital Ampang	Ampang
Malaysia	Pusat Perubatan Universiti Kebangsaan Malaysia	Kuala Lumpur
Mexico	Hospital Civil de Guadalajara Dr Juan I Menchaca	Guadalajara
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador	Mexico
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Monterrey
New Zealand	Auckland City Hospital	Auckland
New Zealand	Waikato Urology Research Ltd	Hamilton
Philippines	De La Salle Health Sciences Institute- DLSUMC	Cavite City
Philippines	Philippine General Hospital	Manila
Russian Federation	S.I. Russian Oncological Research Center n.a. N.N. Blokhin	Moscow
Russian Federation	State Institution "Hematology Research Center" RAMS	Moscow
Singapore	National Neuroscience Institute	Singapore
Singapore	Singapore General Hospital - Parent	Singapore
South Africa	Unitas Hospital	Lyttelton Centurion
Spain	Hospital del Mar	Barcelona
Switzerland	Hôpitaux Universitaires de Genève - HUG	Geneva
Switzerland	Universitaetsspital Zuerich	Zurich
Thailand	Siriraj Hospital	Bangkoknoi
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	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Mercury Street Medical Group	Butte	Montana
United States	Henry Ford Hospital	Detroit	Michigan
United States	Idaho Falls Infectious Diseases PLLC	Idaho Falls	Idaho
United States	Infectious Disease of Indiana	Indianapolis	Indiana
United States	Regional Infection Diseases Infusion Center Inc.	Lima	Ohio
United States	Loyola University Hospital	Maywood	Illinois
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	New York Presbyterian Hospital	New York	New York
United States	Somero Research Corporation	Palm Desert	California
United States	Temple University Health Sciences	Philadelphia	Pennsylvania
United States	University of California Davis Health System	Sacramento	California
United States	University of California at San Francisco	San Francisco	California
United States	Springfield Clinic LLP	Springfield	Illinois
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	UMASS Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Inc	Basilea Pharmaceutica

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Lebanon,  Malaysia,  Mexico,  New Zealand,  Philippines,  Russian Federation,  Singapore,  South Africa,  Spain,  Switzerland,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Overall Response of Success at the End of Intravenous Therapy (EOIV) as Determined by the Data Review Committee (DRC) Based on the Assessments of Clinical and Mycological Responses as Well as Alternative Systemic AFT Use	A Data Review Committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication) without the use of alternative systemic antifungal therapy (AFT) within 48 hours after the last dose of IV study medication.	End of Intravenous Treatment (EOIV) (Days 11-56)
Secondary	Percentage of Participants With Overall Response of Success at Follow Up Visit 1 (FU1-2 Weeks After End of Treatment (EOT)) as Determined by the DRC Based on the Assessments of Clinical, Mycological Responses and Antifungal Therapy (AFT)	A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication), without the use of alternative systemic AFT within 48 hours after the last dose of IV study medication.	End of Treatment (EOT) (Day 56) and FU1 (2 weeks after end of treatment)
Secondary	Percentage of Participants With Overall Response of Success at EOT and Follow Up Visit 2 (FU2) as Determined by the DRC Based on the Assessments of Clinical and Mycological Responses as Well as Alternative Systemic AFT Use at EOT and FU2	A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication), without the use of alternative systemic antifungal therapy AFT within 48 hours after the last dose of IV study medication (for EOT analysis) or for continued treatment of the primary infection, or for recurrent or emergent infection by FU2, with no recurrent or emergent infection by FU2 (for FU2 analysis).	EOT (Day 56) and FU2 (6 weeks after end of treatment)
Secondary	Percentage of Participants With Clinical Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)	A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial).	EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment)
Secondary	Percentage of Participants With Mycological Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)	A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as mycological response (Eradication or Presumed Eradication).	EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment)
Secondary	Percentage of Participants With Mycological Response of Success at Day 7 and EOT as Determined by The Investigator	Success was defined as mycological response (eradication or presumed eradication).	Day 7 and EOT (Day 56)
Secondary	Percentage of Participants With Clinical Response of Success at Day 7 and EOT as Determined by The Investigator	Investigators defined clinical response as success if participants exhibited complete or partial clinical response after evaluation of clinical signs and symptoms.	Day 7 and EOT (Day 56)
Secondary	All-Cause Mortality (ACM) at Day 14 and Day 56	All-cause mortality is represented as the percentage of participants who died on or before the analysis day. Participants who were lost to follow-up (i.e., unknown survival status) before the analysis day were counted as death. All-cause mortality was examined on Day 14 and Day 56.	Day 14 and Day 56
Secondary	Time to First Confirmed Negative Culture	The first confirmed negative blood culture was defined as the first negative blood culture on or after first dose followed by a second negative blood culture at least 24 hours apart without any positive blood cultures in between. A participant without a confirmed negative blood culture was censored on the participant's last visit day. This endpoint was analyzed for mITT participants with candidemia only using the Kaplan-Meier method. Only participants with at least one positive blood culture on or prior to first dose and the culture not resolved prior to first dose were included in this analysis	Day 1 up to FU1 (2 weeks after EOT (Day 56))

External Links

•   Link to results on the Astellas Clinical Study Results website