Study to Compare the Efficacy and Safety of Micafungin Versus Conventional Amphotericin B for the Treatment of Neonatal Candidiasis

Candidiasis Clinical Trial

— MAGIC-2  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00815516
• Other study ID #: 9463-CL-2303
• Secondary ID: 2012-000780-24
• Status: Terminated
• Phase: Phase 3
• First received: December 27, 2008
• Last updated: October 12, 2015
• Start date: February 2013
• Est. completion date: December 2014

Study information

• Verified date: October 2015
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines AgencyChile: Instituto de Salud Pública de ChileArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBrazil: Ministry of HealthPeru: Ministry of HealthMexico: Ministry of HealthCanada: Health CanadaColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosIsrael: Ministry of HealthUkraine: State Pharmacological Center - Ministry of HealthBulgaria: Bulgarian Drug AgencyCroatia: Ministry of Health and Social CareEcuador: Public Health MinistryGreece: National Organization of MedicinesHungary: National Institute of PharmacyKorea: Food and Drug AdministrationPhilippines: Bureau of Food and DrugsRomania: National Medicines AgencySouth Africa: Medicines Control CouncilTaiwan : Food and Drug AdministrationThailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Neonates and young infants will be stratified by estimated gestational age and by world region

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 120 Days

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Candidiasis

Intervention

Drug:
• micafungin
Administered by intravenous infusion
• amphotericin B deoxycholate
Administered by intravenous infusion

Locations

Country	Name	City	State
Brazil	Irmandade da Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte	Minas Gerais
Brazil	Hospital de Base da Faculdade de Medicina	São José do Rio Preto	Sao Paulo
Bulgaria	Spec Hospital for Active Treatment of Children Diseases	Sofia
Canada	McMaster Children's Hospital	Hamilton	Ontario
Colombia	Hospital Pablo Tobon Uribe	Medellin	Antioque
Greece	University Hospital of Patras	Patras
Hungary	Semmelweis Egyetem	Budapest
Israel	Hadassah University Hospital Ein Kerem	Jerusalem
Philippines	Philippine General Hospital	Manila
Romania	Emergency County Clinical Hospital	Cluj-Napoca
Turkey	Cukurova University Medical Faculty	Adana
Ukraine	Municipal Institution "Odesa Regional Children's Hospital"	Odesa
United States	Duke University	Durham	North Carolina
United States	UMDNJ/Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Children's Hospital of Orange County	Orange	California
United States	WakeMed Health and Hospitals	Raleigh	North Carolina
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Canada,  Colombia,  Greece,  Hungary,  Israel,  Philippines,  Romania,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fungal-free Survival	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.	One week after the last dose of study drug (maximum of 49 days)	No
Secondary	Time to Mycological Clearance of Invasive Candidiasis	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.	From first dose up to 30 days after the last dose of study drug (maximum of 72 days)	No
Secondary	Fungal-free Survival at End of Study Drug Therapy in Infants With End-organ Dissemination	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.	The end of study drug therapy; maximum of 42 days	No
Secondary	Fungal-free Survival One Week After Last Dose of Study Drug in Infants With End-organ Dissemination	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.	One week after the last dose of study drug (maximum of 49 days)	No
Secondary	Percentage of Participants With Emergent Fungal Infections	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.	Up to 30 days after the last dose of study drug (maximum of 72 days)	No
Secondary	Percentage of Participants With Recurrent Fungal Infections	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.	Up to 30 days after the last dose of study drug (maximum of 72 days)	No
Secondary	Time to Positive Clinical Response	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.	From first dose up to 30 days after the last dose of study drug (maximum of 72 days)	No
Secondary	Clinical Response at the End of Study Drug Therapy	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.	Baseline and end of study drug therapy; maximum of 42 days	No
Secondary	Clinical Response One Week After Last Dose of Study Drug	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.	Baseline and one week after the last dose of study drug (maximum of 49 days)	No
Secondary	Mycological Response at End of Study Drug Therapy	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.	End of study drug therapy; maximum of 42 days	No
Secondary	Mycological Response One Week After Last Dose of Study Drug	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.	One week after the last dose of study drug (maximum of 49 days)	No
Secondary	Follow-up Status for Infants With End-organ Assessments	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.	Baseline and 30 days after the last dose of study drug (maximum of 72 days)	No
Secondary	Plasma Micafungin Concentration		15 minutes post intravenous infusion (IV), 4-8 hours post IV and 15-24 hours post IV	No

External Links

•   Link to results on Astellas Clinical Study Results Web site