Study to Compare the Efficacy and Safety of Micafungin Versus Conventional Amphotericin B for the Treatment of Neonatal Candidiasis (MAGIC-2)

This study has been terminated.
(It was decided to discontinue the study due to insufficient recruitment.)
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT00815516
First received: December 27, 2008
Last updated: October 12, 2015
Last verified: October 2015
  Purpose
The study will evaluate how effective and how safe the drug micafungin is when compared to the drug amphotericin B deoxycholate in treating neonates and young infants with certain fungal infections.

Condition Intervention Phase
Candidiasis
Drug: micafungin
Drug: amphotericin B deoxycholate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Multi-Center Study to Compare the Efficacy and Safety of Micafungin Versus Amphotericin B Deoxycholate for the Treatment of Neonatal Candidiasis

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Fungal-free Survival [ Time Frame: One week after the last dose of study drug (maximum of 49 days) ] [ Designated as safety issue: No ]

    Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive at one week following the last dose of study drug with a mycological response of eradication and no requirement for alternative systemic antifungal therapy for continued treatment.

    Eradication was defined as culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 hours apart, or for Candida meningitis and/or candiduria, 1 negative culture.



Secondary Outcome Measures:
  • Time to Mycological Clearance of Invasive Candidiasis [ Time Frame: From first dose up to 30 days after the last dose of study drug (maximum of 72 days) ] [ Designated as safety issue: No ]

    Time to mycological clearance of invasive candidiasis is defined as the time from first dose to the day of mycological eradication for baseline invasive candidiasis infection.

    Eradication was defined as a culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 hours apart, or for for Candida meningitis and/or candiduria, 1 negative culture.

    Infants without eradication during the treatment period and who survived were censored at one day after the end of treatment. Infants without eradication who died before completing the treatment period or were lost to follow-up during the treatment were censored at their death or last contact day.


  • Fungal-free Survival at End of Study Drug Therapy in Infants With End-organ Dissemination [ Time Frame: The end of study drug therapy; maximum of 42 days ] [ Designated as safety issue: No ]
    Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive at the end of study drug therapy with a mycological response of eradication based upon the DRP assessment and no requirement for alternative systemic antifungal therapy for continued treatment.

  • Fungal-free Survival One Week After Last Dose of Study Drug in Infants With End-organ Dissemination [ Time Frame: One week after the last dose of study drug (maximum of 49 days) ] [ Designated as safety issue: No ]
    Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive one week after last dose of study drug with a mycological response of eradication based upon the DRP assessment and no requirement for alternative systemic antifungal therapy for continued treatment.

  • Percentage of Participants With Emergent Fungal Infections [ Time Frame: Up to 30 days after the last dose of study drug (maximum of 72 days) ] [ Designated as safety issue: No ]

    An emergent fungal infection is defined as

    • An invasive fungal infection which is detected at any time during the study that is a non-Candida organism, or
    • An invasive fungal infection which is detected during the treatment or post-treatment period with a Candida species identified other than those detected at Baseline. If this occurred within 96 hours of the first dose of study drug, the infection was considered part of the final diagnosis of enrolling infection and not an emergent infection.

  • Percentage of Participants With Recurrent Fungal Infections [ Time Frame: Up to 30 days after the last dose of study drug (maximum of 72 days) ] [ Designated as safety issue: No ]
    A recurrent infection is defined as a systemic fungal infection in an infant with eradication at the end of study drug therapy, who developed positive blood cultures or a mycologically confirmed deep-seated Candida infection, with the same species as the enrolling infection.

  • Time to Positive Clinical Response [ Time Frame: From first dose up to 30 days after the last dose of study drug (maximum of 72 days) ] [ Designated as safety issue: No ]

    Time to a positive clinical response is defined as the time from the first dose to the day during the treatment period that a positive clinical response (defined as a complete response or partial response) is observed for the first time, assessed by the Investigator.

    Complete Response is defined as the resolution of all attributable signs related to fungal infection, if present at baseline and Partial Response is defined as improvement in attributable signs related to the fungal infection, if present at baseline.

    Infants without positive responses and who survived were censored at one day post the end of treatment. Infants without positive responses who died before completing the treatment period, or were lost to follow-up during the treatment were censored at their death or last contact day.


  • Clinical Response at the End of Study Drug Therapy [ Time Frame: Baseline and end of study drug therapy; maximum of 42 days ] [ Designated as safety issue: No ]

    Clinical response assessments were based on the following definitions and assessed by the DRP:

    • Complete Response: Resolution of all attributable signs related to fungal infection, if present at baseline.
    • Partial Response: Improvement in attributable signs related to the fungal infection, if present at baseline.
    • Stabilization: Minor improvement or no change in attributable signs related to the fungal infection, if present at baseline, and infant continued on therapy without deterioration.
    • Progression: Deterioration in attributable signs related to the fungal infection, if present at baseline; or if death occurred presumably related to a fungal infection.

  • Clinical Response One Week After Last Dose of Study Drug [ Time Frame: Baseline and one week after the last dose of study drug (maximum of 49 days) ] [ Designated as safety issue: No ]

    Clinical response assessments were based on the following definitions and assessed by the DRP:

    • Complete Response: Resolution of all attributable signs related to fungal infection, if present at baseline.
    • Partial Response: Improvement in attributable signs related to the fungal infection, if present at baseline.
    • Stabilization: Minor improvement or no change in attributable signs related to the fungal infection, if present at baseline, and infant continued on therapy without deterioration.
    • Progression: Deterioration in attributable signs related to the fungal infection, if present at baseline; or if death occurred presumably related to a fungal infection.

  • Mycological Response at End of Study Drug Therapy [ Time Frame: End of study drug therapy; maximum of 42 days ] [ Designated as safety issue: No ]

    Mycological response assessments were based on the following definitions and assessed by the DRP:

    • Eradication: Culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 h apart; for Candida meningitis and/or candiduria, 1 negative culture.
    • Persistence: Continued isolation or histological documentation from a normally sterile site.

  • Mycological Response One Week After Last Dose of Study Drug [ Time Frame: One week after the last dose of study drug (maximum of 49 days) ] [ Designated as safety issue: No ]

    Mycological response assessments were based on the following definitions and assessed by the DRP:

    • Eradication: Culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 h apart; for Candida meningitis and/or candiduria, 1 negative culture.
    • Persistence: Continued isolation or histological documentation from a normally sterile site.

  • Follow-up Status for Infants With End-organ Assessments [ Time Frame: Baseline and 30 days after the last dose of study drug (maximum of 72 days) ] [ Designated as safety issue: No ]

    End-organ dissemination was assessed through abdominal ultrasound and/or computed tomography (CT), echocardiogram, head imaging and retinal exam. Each specific finding, documented by 1 of these techniques, was evaluated as follows:

    • Improvement: Improvement in size, number or density of identified lesions. Complete response was not expected but may have been documented.
    • Stabilization: Minor improvement or no change in size, number or density of identified lesions.
    • Worsening: Increase in size or number of identified lesions.

  • Plasma Micafungin Concentration [ Time Frame: 15 minutes post intravenous infusion (IV), 4-8 hours post IV and 15-24 hours post IV ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: February 2013
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Micafungin
Infants received micafungin at a dose of 10 mg/kg per day by intravenous infusion for a minimum of 21 days to a maximum of 28 days for infants without end-organ dissemination or for a maximum of 42 days for infants with end-organ dissemination.
Drug: micafungin
Administered by intravenous infusion
Other Names:
  • Mycamine
  • FK463
Active Comparator: Amphotericin B deoxycholate
Infants received amphotericin B deoxycholate (CAB) at a dose of 1.0 mg/kg per day by intravenous infusion for a minimum of 21 days to a maximum of 28 days for infants without end-organ dissemination or for a maximum of 42 days for infants with end-organ dissemination.
Drug: amphotericin B deoxycholate
Administered by intravenous infusion
Other Names:
  • Fungizone
  • Conventional amphotericin B (CAB)
  • Amphotericin B for injection

Detailed Description:
Neonates and young infants will be stratified by estimated gestational age and by world region
  Eligibility

Ages Eligible for Study:   up to 120 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Infant greater than 48 hours of life after birth up to day of life 120 at the time of culture acquisition
  • Diagnosis of proven invasive candidiasis within 4 days prior to study start
  • Subject's parent or legal guardian agrees not to allow subject to participate in another study with another investigational drug while on treatment.

Exclusion Criteria:

  • Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or systemic amphotericin B product
  • Infant who has received more than 48 hours of systemic antifungal therapy prior to the first dose of study drug
  • Infant who has a breakthrough systemic fungal infection while receiving amphotericin B product or an echinocandin as prophylaxis
  • Infant who has failed prior systemic antifungal therapy for this episode of invasive candidiasis
  • Infant who is co-infected with a non-Candida fungal organism
  • Infant whose positive yeast cultures are solely from an indwelling bladder catheter (unless obtained at the time the indwelling catheter was placed) or sputum.
  • Infant previously enrolled in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00815516

Locations
United States, California
Children's Hospital of Orange County
Orange, California, United States, 92868
United States, New Jersey
UMDNJ/Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08901
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
WakeMed Health and Hospitals
Raleigh, North Carolina, United States, 27610
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Brazil
Irmandade da Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, Minas Gerais, Brazil, 30150-221
Hospital de Base da Faculdade de Medicina
São José do Rio Preto, Sao Paulo, Brazil, 15090-000
Bulgaria
Spec Hospital for Active Treatment of Children Diseases
Sofia, Bulgaria, 1606
Canada, Ontario
McMaster Children's Hospital
Hamilton, Ontario, Canada, L8N 3Z5
Colombia
Hospital Pablo Tobon Uribe
Medellin, Antioque, Colombia, 574
Greece
University Hospital of Patras
Patras, Greece, 26504
Hungary
Semmelweis Egyetem
Budapest, Hungary, 8200
Israel
Hadassah University Hospital Ein Kerem
Jerusalem, Israel, 91120
Philippines
Philippine General Hospital
Manila, Philippines
Romania
Emergency County Clinical Hospital
Cluj-Napoca, Romania, 400006
Turkey
Cukurova University Medical Faculty
Adana, Turkey, 1330
Ukraine
Municipal Institution "Odesa Regional Children's Hospital"
Odesa, Ukraine, 65031
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Senior Medical Director Astellas Pharma Global Development
  More Information

Additional Information:
No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT00815516     History of Changes
Other Study ID Numbers: 9463-CL-2303  2012-000780-24 
Study First Received: December 27, 2008
Results First Received: August 14, 2015
Last Updated: October 12, 2015
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Chile: Instituto de Salud Pública de Chile
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: Ministry of Health
Peru: Ministry of Health
Mexico: Ministry of Health
Canada: Health Canada
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Israel: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
Bulgaria: Bulgarian Drug Agency
Croatia: Ministry of Health and Social Care
Ecuador: Public Health Ministry
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Korea: Food and Drug Administration
Philippines: Bureau of Food and Drugs
Romania: National Medicines Agency
South Africa: Medicines Control Council
Taiwan : Food and Drug Administration
Thailand: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
candidiasis
candida
Neonate
candidemia
Micafungin
Mycamine
amphotericin B deoxycholate

Additional relevant MeSH terms:
Candidiasis
Mycoses
Amphotericin B
Amphotericin B, deoxycholate drug combination
Deoxycholic Acid
Liposomal amphotericin B
Micafungin
Amebicides
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Antiparasitic Agents
Antiprotozoal Agents
Cholagogues and Choleretics
Gastrointestinal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on February 10, 2016