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

Phase 3
Completed
Conditions
Mycoses
Candidiasis, Invasive
Candidemia
Interventions
Registration Number
NCT00413218
Lead Sponsor
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
450
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Isavuconazole (ISA)IsavuconazoleParticipants 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.
Caspofungin (CAS)/VoriconazoleCaspofunginParticipants 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.
Caspofungin (CAS)/VoriconazoleVoriconazoleParticipants 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.
Primary Outcome Measures
NameTimeMethod
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 UseEnd 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
NameTimeMethod
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 FU2EOT (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)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 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)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 Mycological Response of Success at Day 7 and EOT as Determined by The InvestigatorDay 7 and EOT (Day 56)

Success was defined as mycological response (eradication or presumed eradication).

Percentage of Participants With Mycological Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)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 Clinical Response of Success at Day 7 and EOT as Determined by The InvestigatorDay 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 56Day 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 CultureDay 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

Trial Locations

Locations (113)

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Somero Research Corporation

🇺🇸

Palm Desert, California, United States

University of California Davis Health System

🇺🇸

Sacramento, California, United States

University of California at San Francisco

🇺🇸

San Francisco, California, United States

Idaho Falls Infectious Diseases PLLC

🇺🇸

Idaho Falls, Idaho, United States

Loyola University Hospital

🇺🇸

Maywood, Illinois, United States

Springfield Clinic LLP

🇺🇸

Springfield, Illinois, United States

Infectious Disease of Indiana

🇺🇸

Indianapolis, Indiana, United States

Ochsner Clinic Foundation

🇺🇸

New Orleans, Louisiana, United States

University of Maryland School of Medicine

🇺🇸

Baltimore, Maryland, United States

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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States

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