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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00413218
Recruitment Status : Completed
First Posted : December 19, 2006
Results First Posted : August 1, 2017
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
Basilea Pharmaceutica
Information provided by (Responsible Party):
Astellas Pharma Inc

Brief 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.

Condition or disease Intervention/treatment Phase
Candidiasis, Invasive Candidemia Mycoses Drug: Isavuconazole Drug: Caspofungin Drug: Voriconazole Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : March 8, 2007
Actual Primary Completion Date : March 3, 2015
Actual Study Completion Date : March 3, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Yeast Infections

Arm Intervention/treatment
Experimental: Isavuconazole (ISA)
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Drug: Isavuconazole
Administered by intravenous infusion.
Other Names:
  • ASP9766
  • BAL8557

Active Comparator: Caspofungin (CAS)/Voriconazole
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Drug: Caspofungin
Administered by intravenous infusion.
Other Name: Cancidas

Drug: Voriconazole
Administered by intravenous infusion.
Other Name: VFend




Primary Outcome Measures :
  1. 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 [ Time Frame: End of Intravenous Treatment (EOIV) (Days 11-56) ]
    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.


Secondary Outcome Measures :
  1. 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) [ Time Frame: End of Treatment (EOT) (Day 56) and FU1 (2 weeks after end of treatment) ]
    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.

  2. 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 [ Time Frame: EOT (Day 56) and FU2 (6 weeks after end of treatment) ]
    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).

  3. Percentage of Participants With Clinical Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC) [ Time Frame: EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment) ]
    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).

  4. Percentage of Participants With Mycological Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC) [ Time Frame: EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment) ]
    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).

  5. Percentage of Participants With Mycological Response of Success at Day 7 and EOT as Determined by The Investigator [ Time Frame: Day 7 and EOT (Day 56) ]
    Success was defined as mycological response (eradication or presumed eradication).

  6. Percentage of Participants With Clinical Response of Success at Day 7 and EOT as Determined by The Investigator [ Time Frame: Day 7 and EOT (Day 56) ]
    Investigators defined clinical response as success if participants exhibited complete or partial clinical response after evaluation of clinical signs and symptoms.

  7. All-Cause Mortality (ACM) at Day 14 and Day 56 [ Time Frame: 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.

  8. Time to First Confirmed Negative Culture [ Time Frame: Day 1 up to FU1 (2 weeks after EOT (Day 56)) ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00413218


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Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-0006
United States, California
Somero Research Corporation
Palm Desert, California, United States, 92211
University of California Davis Health System
Sacramento, California, United States, 95817
University of California at San Francisco
San Francisco, California, United States, 94143
United States, Idaho
Idaho Falls Infectious Diseases PLLC
Idaho Falls, Idaho, United States, 83404
United States, Illinois
Loyola University Hospital
Maywood, Illinois, United States, 60153
Springfield Clinic LLP
Springfield, Illinois, United States, 62701
United States, Indiana
Infectious Disease of Indiana
Indianapolis, Indiana, United States, 46280
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Maryland
University of Maryland School of Medicine
Baltimore, Maryland, United States, 21201
United States, Massachusetts
UMASS Memorial Medical Center
Worcester, Massachusetts, United States, 01655
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Montana
Mercury Street Medical Group
Butte, Montana, United States, 59701
United States, New Jersey
Jersey Shore University Medical Center
Neptune, New Jersey, United States, 07753
United States, New York
New York Presbyterian Hospital
New York, New York, United States, 10065
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Regional Infection Diseases Infusion Center Inc.
Lima, Ohio, United States, 45801
United States, Pennsylvania
Temple University Health Sciences
Philadelphia, Pennsylvania, United States, 19140
Argentina
Hospital Britanico de Buenos Aires
Capital Federal, Argentina, C1280AEB
Hospital General de Agudos Dr. Carlos G. Durand
Capital Federal, Argentina, C1405DCS
Hospital Italiano de Buenos Aires
Ciudad Autonoma, Argentina, 1181
Instituto Medico Especializado Alexander Fleming
Ciudad Autonoma, Argentina, 1426
Hospital General de Agudos Dr. Cosme Argerich
La Boca, Argentina, 1157
Australia
Fremantle Hospital
Fremantle, Australia, 6160
Mater Adult Hospital
South Brisbane, Australia
Westmead Hospital
Westmead, Australia
Princess Alexandra Hospital
Woolloongabba, Australia, 4102
Belgium
Institut Jules Bordet
Brussels, Belgium, 1000
Universitair Ziekenhuis Brussel
Brussels, Belgium, 1090
ULB Hôpital Erasme
Bruxelles, Belgium, 1070
Universitair Ziekenhuis Gent
Gent, Belgium, 9000
Universitaire Ziekenhuizen Leuven
Leuven, Belgium, 3000
Brazil
Hospital Felicio Rocho
Belo Horizonte, Brazil, 30110-908
Hospital das Clinicas da Universidade Federal de Minas Gerai
Belo Horizonte, Brazil, 30130-100
Santa Casa de Misericordia de Belo Horizonte
Belo Horizonte, Brazil, 30150-221
Hospital das Clinicas da UFPR
Curitiba, Brazil, 80060-150
Hospital Nossa Senhora das Gracas
Curitiba, Brazil, 80810-040
Hospital Sao Lucas - PUCRS
Porto Alegre, Brazil, 90610-000
Irmandade da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Brazil
Hospital Universitario Clementino Fraga Filho
Rio de Janeiro, Brazil, 21941-913
Hospital Universitario de Santa Maria
Santa Maria, Brazil, 97105-900
Universidade Federal de Sao Paulo - UNIFESP
São Paulo, Brazil, 04020-002
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Hamilton Health Sciences - Henderson Site
Hamilton, Ontario, Canada, L8V 1C3
Queen's University
Kingston, Ontario, Canada, K7L 3N6
The Ottawa Hospital - General Campus
Ottawa, Ontario, Canada, K1H 8L6
University Health Network - Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
Hôpital Maisonneuve - Rosemont
Montreal, Quebec, Canada, H1T 2M4
Chile
Hospital Dr. Sotero del Rio
Puente Alto Santiago, Chile
Hospital del Salvador
Santiago, Chile
Hospital Dr. Hernan Henriquez Aravena
Temuco, Chile, 4780000
China
West China Hospital of Sichuan University
Chengdu, China, 610041
Huashan Hospital Fudan University
Shanghai, China, 200040
France
Hôpital Hautepierre
Strasbourg, France, 67048
Hôpital de Brabois Adultes
Vandoeuvre les Nancy, France, 54511
Germany
Charite Campus Mitte
Berlin, Germany, 10117
Universitaetsklinikum Freiburg
Freiburg, Germany
Universitaet Koeln
Koeln, Germany, 50937
Klinikum St. Georg
Leipzig, Germany, 04129
Universitaetsklinik Leipzig
Leipzig, Germany, 04289
Universitaetsklinikum Leipzig
Luebeck, Germany
Universitaetsklinikum Wuerzburg
Wuerzburg, Germany, 97080
Hungary
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
Debrecen, Hungary, 4032
Petz Aladar Megyei Oktato Korhaz
Györ, Hungary, 9024
India
Max Super Speciality Hospital
New Delhi, Delhi, India, 110017
Metro Centre for Respiratory Diseases
Noida, Delhi, India, 201301
Kasturba Medical College and Hospital
Mangalore, Karna, India, 575001
Kasturba Medical College K. M. C. Hospital
Manipal, Karna, India, 576104
Amrita Institute Of Medical Science
Cochin, Kerala, India, 682041
Deenanath Mangeshkar Hospital and Research Centre
Pune, Mahara, India, 411004
Apollo Hospitals Educational & Research Foundation
Chennai, India
Nizam's Institute of Medical Sciences
Hyderabad, India, 500082
AMRI Hospital
Kolkata, India, 700098
Christian Medical College & Hospital
Vellore Tamilnadu, India
Israel
Ha Emek Medical Center
Afula, Israel, 18101
Rambam Health Care Campus
Haifa, Israel, 31096
Wolfson Medical Center
Holon, Israel, 58100
Hadassah Universtiy Hospital - Ein Kerem
Jerusalem, Israel, 91200
Sapir Medical Center, Meir Hospital
Kfar-Saba, Israel, 44281
Rabin MC
Petah, Israel, 49100
Chaim Sheba Medical Center
Ramat Gan, Israel, 52621
Sourasky MC Ichilov Hospital Tel Aviv
Tel Aviv, Israel, 64239
Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Ma
Bologna, Italy, 40138
Azienda Ospedaliera Spedali Civili di Brescia
Brescia, Italy, 25126
Ente Ospedaliero Ospedeli Galliera
Genova, Italy, 16128
Azienda Ospedaliero Universitaria San Martino
Genova, Italy, 16132
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
Verona, Italy, 37134
Lebanon
AUB Medical Center
Beirut, Lebanon, 11-0236
Rafik Hariri Uni Hospital
Beirut, Lebanon, 5244
Malaysia
Hospital Ampang
Ampang, Malaysia, 68000
Pusat Perubatan Universiti Kebangsaan Malaysia
Kuala Lumpur, Malaysia, 56000
Mexico
Hospital Civil de Guadalajara Fray Antonio Alcalde
Guadalajara, Mexico, 44280
Hospital Civil de Guadalajara Dr Juan I Menchaca
Guadalajara, Mexico, 44340
Instituto Nacional de Ciencias Medicas y Nutricion Salvador
Mexico, Mexico, 14000
Hospital Universitario Dr Jose Eleuterio Gonzalez
Monterrey, Mexico, 64460
New Zealand
Auckland City Hospital
Auckland, New Zealand
Waikato Urology Research Ltd
Hamilton, New Zealand
Philippines
De La Salle Health Sciences Institute- DLSUMC
Cavite City, Philippines
Philippine General Hospital
Manila, Philippines
Russian Federation
S.I. Russian Oncological Research Center n.a. N.N. Blokhin
Moscow, Russian Federation, 115478
State Institution "Hematology Research Center" RAMS
Moscow, Russian Federation, 125167
Singapore
Singapore General Hospital - Parent
Singapore, Singapore, 169608
National Neuroscience Institute
Singapore, Singapore, 308433
South Africa
Unitas Hospital
Lyttelton Centurion, South Africa, 0157
Spain
Hospital del Mar
Barcelona, Spain, 08003
Switzerland
Hôpitaux Universitaires de Genève - HUG
Geneva, Switzerland
Universitaetsspital Zuerich
Zurich, Switzerland
Thailand
Siriraj Hospital
Bangkoknoi, Thailand, 10700
Songklanagarind Hospital
Hat Yai, Thailand, 90110
Maharat Nakhon Ratchasima Hospital
Muang, Thailand, 30000
Srinagarind Hospital
Muang, Thailand, 40002
Maharaj Nakorn Chiang Mai Hospital
Muang, Thailand, 50200
Ramathibodi Hospital
Ratchathewi, Thailand, 10400
Sponsors and Collaborators
Astellas Pharma Inc
Basilea Pharmaceutica
Investigators
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Study Director: Medical Director Astellas Pharma Global Development

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00413218     History of Changes
Obsolete Identifiers: NCT00444366
Other Study ID Numbers: 9766-CL-0105
WSA-CS-008 ( Other Identifier: Basilea Pharmaceutica Ltd )
2006-003951-18 ( EudraCT Number )
First Posted: December 19, 2006    Key Record Dates
Results First Posted: August 1, 2017
Last Update Posted: February 15, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/

Keywords provided by Astellas Pharma Inc:
Invasive Candida infections
BAL8557
ASP9766
Isavuconazole
Candidemia
Candidemia and other invasive candida infections
Phase III study

Additional relevant MeSH terms:
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Infection
Mycoses
Candidiasis
Candidemia
Candidiasis, Invasive
Fungemia
Sepsis
Invasive Fungal Infections
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Voriconazole
Caspofungin
Isavuconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors