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

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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

Tracking Information
First Submitted Date  ICMJE December 18, 2006
First Posted Date  ICMJE December 19, 2006
Results First Submitted Date  ICMJE July 5, 2017
Results First Posted Date  ICMJE August 1, 2017
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE March 8, 2007
Actual Primary Completion Date March 3, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2006)
Overall response: Resolution of signs and symptoms of infection plus mycological (presumed) eradication
Change History Complete list of historical versions of study NCT00413218 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2017)
  • 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.
  • 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).
  • 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).
  • 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).
  • 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).
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2006)
  • Mycological response
  • Time to First Confirmed Negative Culture
  • All-cause mortality
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Isavuconazole (BAL8557) in the Treatment of Candidemia and Other Invasive Candida Infections
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Candidiasis, Invasive
  • Candidemia
  • Mycoses
Intervention  ICMJE
  • Drug: Isavuconazole
    Administered by intravenous infusion.
    Other Names:
    • ASP9766
    • BAL8557
  • Drug: Caspofungin
    Administered by intravenous infusion.
    Other Name: Cancidas
  • Drug: Voriconazole
    Administered by intravenous infusion.
    Other Name: VFend
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Isavuconazole
  • 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.
    Interventions:
    • Drug: Caspofungin
    • Drug: Voriconazole
Publications * McCormack PL. Isavuconazonium: first global approval. Drugs. 2015 May;75(7):817-22. doi: 10.1007/s40265-015-0398-6. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 15, 2015)
450
Original Enrollment  ICMJE
 (submitted: December 18, 2006)
526
Actual Study Completion Date  ICMJE March 3, 2015
Actual Primary Completion Date March 3, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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,   United States
Removed Location Countries Colombia,   Egypt,   Korea, Republic of,   Netherlands,   Poland,   Turkey,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT00413218
Other Study ID Numbers  ICMJE 9766-CL-0105
WSA-CS-008 ( Other Identifier: Basilea Pharmaceutica Ltd )
2006-003951-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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/
Responsible Party Astellas Pharma Inc
Study Sponsor  ICMJE Astellas Pharma Inc
Collaborators  ICMJE Basilea Pharmaceutica
Investigators  ICMJE
Study Director: Medical Director Astellas Pharma Global Development
PRS Account Astellas Pharma Inc
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP