CandidiasisPhase 3MAGIC-2NCT00815516
Study to Compare the Efficacy and Safety of Micafungin Versus Conventional Amphotericin B for the Treatment of Neonatal Candidiasis
A Phase 3 study testing micafungin and amphotericin B deoxycholate in people with Candidiasis, run by Astellas Pharma Global Development, Inc. at 17 sites in 12 countries.
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. Read more about this study
- Who is it for?
- Ages 48 hours to 120 days
- Conditions the study is for
- Candidiasis
- What is being tested?
- micafungin and amphotericin B deoxycholate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 17 sitesin 12 countries
- Study dates
- Feb 2013to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 48 hours to 120 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
17 sites in 12 countries.
17 sites in 12 countries
United States5 sites
Duke University
Durham, North Carolina, 27710
UMDNJ/Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
Children's Hospital of Orange County
Orange, California, 92868
WakeMed Health and Hospitals
Raleigh, North Carolina, 27610
Virginia Commonwealth University
Richmond, Virginia, 23298
Brazil2 sites
Irmandade da Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, Minas Gerais, 30150-221
Hospital de Base da Faculdade de Medicina
São José do Rio Preto, São Paulo, 15090-000
Bulgaria1 site
Spec Hospital for Active Treatment of Children Diseases
Sofia, 1606
Turkey (Türkiye)1 site
Cukurova University Medical Faculty
Adana, 1330
Ukraine1 site
Municipal Institution "Odesa Regional Children's Hospital"
Odesa, 65031
About this study
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
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.
Read the detailed description
Neonates and young infants will be stratified by estimated gestational age and by world region
- Conditions
- Candidiasis
- Being tested
- micafungin, amphotericin B deoxycholate
- Keywords
- candidiasis, candida, Neonate, candidemia, Micafungin, Mycamine, amphotericin B deoxycholate
- Medical subject headings
- Candidiasis, Torulopsis, Candidemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
micafunginDrug
Also called Mycamine, FK463
Administered by intravenous infusion
amphotericin B deoxycholateDrug
Also called Fungizone, Conventional amphotericin B (CAB), Amphotericin B for injection
Administered by intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Micafungin | Experimental | 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. Receives: Drug: micafungin |
| Amphotericin B deoxycholate | Active comparator | 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. Receives: Drug: amphotericin B deoxycholate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: One week after the last dose of study drug (maximum of 49 days)
Secondary outcomes (12)
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.
Measured: From first dose up to 30 days after the last dose of study drug (maximum of 72 days)
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.
Measured: The end of study drug therapy; maximum of 42 days
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.
Measured: One week after the last dose of study drug (maximum of 49 days)
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.
Measured: Up to 30 days after the last dose of study drug (maximum of 72 days)
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.
Measured: Up to 30 days after the last dose of study drug (maximum of 72 days)
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.
Measured: From first dose up to 30 days after the last dose of study drug (maximum of 72 days)
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.
Measured: Baseline and end of study drug therapy; maximum of 42 days
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.
Measured: Baseline and one week after the last dose of study drug (maximum of 49 days)
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.
Measured: End of study drug therapy; maximum of 42 days
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.
Measured: One week after the last dose of study drug (maximum of 49 days)
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.
Measured: Baseline and 30 days after the last dose of study drug (maximum of 72 days)
Plasma Micafungin Concentration
Measured: 15 minutes post intravenous infusion (IV), 4-8 hours post IV and 15-24 hours post IV
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2008 (estimated)
- Study startFeb 2013
- Primary completionDec 2014
- Study completionDec 2014
Why it stopped: It was decided to discontinue the study due to insufficient recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CandidiasisStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Senior Medical Director, Study director, Astellas Pharma Global Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00815516
- Sponsor's protocol ID
- 9463-CL-2303
- Other IDs
- 2012-000780-24
- Acronym
- MAGIC-2
- Status last verified
- Oct 2015
- First submitted
- 27 Dec 2008
- Last updated
- 4 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Benjamin DK Jr, Kaufman DA, Hope WW, Smith PB, Arrieta A, Manzoni P, Kovanda LL, Lademacher C, Isaacson B, Jednachowski D, Wu C, Kaibara A, Walsh TJ. A Phase 3 Study of Micafungin Versus Amphotericin B Deoxycholate in Infants With Invasive Candidiasis. Pediatr Infect Dis J. 2018 Oct;37(10):992-998. doi: 10.1097/INF.0000000000001996.
PubMed 29596222
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00815516
- Acronym / sponsor ID
- MAGIC-2 / 9463-CL-2303
- Conditions
- Candidiasis
- Keywords
- candidiasis, candida, Neonate, candidemia, Micafungin, Mycamine, amphotericin B deoxycholate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: It was decided to discontinue the study due to insufficient recruitment.
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 30 Dec 2008 (estimated)
- Results
- Posted 15 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Neonates and young infants will be stratified by estimated gestational age and by world region
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Micafungin | Experimental | Drug: micafunginInfants 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. |
| Amphotericin B deoxycholate | Active comparator | Drug: amphotericin B deoxycholateInfants 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. |
Who may qualify
- Ages
- 48 hours to 120 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| micafunginAlso: Mycamine, FK463Administered by intravenous infusion | Drug | Micafungin |
| amphotericin B deoxycholateAlso: Fungizone, Conventional amphotericin B (CAB), Amphotericin B for injectionAdministered by intravenous infusion | Drug | Amphotericin B deoxycholate |
Primary outcome
Fungal-free Survival
Time frame: One week after the last dose of study drug (maximum of 49 days)
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.
12 secondary outcomes
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)
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
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)
Percentage of Participants With Emergent Fungal Infections
Time frame: Up to 30 days after the last dose of study drug (maximum of 72 days)
Percentage of Participants With Recurrent Fungal Infections
Time frame: Up to 30 days after the last dose of study drug (maximum of 72 days)
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)
Clinical Response at the End of Study Drug Therapy
Time frame: Baseline and end of study drug therapy; maximum of 42 days
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)
Mycological Response at End of Study Drug Therapy
Time frame: End of study drug therapy; maximum of 42 days
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)
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)
Plasma Micafungin Concentration
Time frame: 15 minutes post intravenous infusion (IV), 4-8 hours post IV and 15-24 hours post IV
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29596222Benjamin DK Jr, Kaufman DA, Hope WW, Smith PB, Arrieta A, Manzoni P, Kovanda LL, Lademacher C, Isaacson B, Jednachowski D, Wu C, Kaibara A, Walsh TJ. A Phase 3 Study of Micafungin Versus Amphotericin B Deoxycholate in Infants With Invasive Candidiasis. Pediatr Infect Dis J. 2018 Oct;37(10):992-998. doi: 10.1097/INF.0000000000001996.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Senior Medical Director study director
Astellas Pharma Global Development
17 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing micafungin and amphotericin B deoxycholate in people with Candidiasis, run by Astellas Pharma Global Development, Inc. at 17 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Brazil, Bulgaria, Canada, Colombia and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fungal-free Survival (time frame: One week after the last dose of study drug (maximum of 49 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00815516, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2015.