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CompletedNCT03421002Updated Nov 18, 2024

Determination of Levels of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis

A Phase 2 interventional study of Micafungin in Candidiasis, Systemic and Candida Meningitis, sponsored by Astellas Pharma Global Development, Inc.. Completed at 2 sites in Italy. Open to participants aged 1 Day to 180 Days. Per ClinicalTrials.gov, last updated 2024-11-18.

Sponsored by Astellas Pharma Global Development, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
35
Allocation
Not applicable
Ages
1 Day to 180 Days
Sex
All
01

Study summary

The primary purpose of this study is to evaluate the pharmacokinetic profile of micafungin administered to neonates suffering from systemic candidiasis. This study will also evaluate the proportion of success and of failure of the therapy with micafungin among treated neonates and will identify a conversion factor to relate plasma levels of micafungin into capillary and venous blood measured through blood samples from the heel and from a peripheral vein, collected simultaneously. Safety of micafungin in neonates will also be assessed.

02

Conditions studied

  • Candidiasis, Systemic
  • Candida Meningitis

Keywords

  • candida meningitis
  • Mycamine
  • candidiasis, systemic
  • micafungin
03

Who can participate

Ages eligible
1 Day to 180 Days
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Infection by systemic candidiasis Systemic candidiasis is diagnosed in case of worsening of clinical conditions while on therapy with antibiotics, in case of isolation of candida from at least one sample collected from a normally sterile site (Blood, CSF, Urine, Peritoneal Fluid) and/or from at least two non contiguous sites (tracheal aspirate, gastric aspirate, faeces) and/or positivity to candida through polymerase chain reaction (PCR)(Septifast test), associated with at least one clinical symptom (fever or hypothermia, mottled skin, feeding difficulties, muscular hypotonia or hypertonia, apnoea crisis, bradycardia, tachycardia, hypotension, dyspnea, polypnea, desaturation) and one laboratory symptom (white blood cell [WBC] ≤5000/mm3 or WBC ≥20.000/mm3, immature to total neutrophil ratio [I/T ratio] >2, Platelet count ≤100.000/mm3, C-reactive Protein >0,5 mg/dL, Standard Base Excess >-7 mmol/L, CSF pleocytosis-cells ≥ 6) and/or positivity to test Enzyme Linked Immuno-Sorbent Assay (ELISA) for the mannan antigen (≥125 pg/ml).
  • Neonates affected by candida meningitis and/or hydrocephalus due to candida infection and/or bearing external ventricular derivation, until enrollment of at least 4 subjects with this characteristics.
  • Parents of neonates, or legal representative, able to consent and comply with protocol requirements.
  • Survival expectation not inferior to 3 days.

Exclusion criteria

Exclusion Criteria:

  • Acute hepatopathy (ammonium > 200 µg/dL) or chronic hepatopathy.
  • Known allergy or hypersensitivity to echinocandins or any of the excipients present in the formulation of the investigational product.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
35 participants (actual)

Study arms

  • Experimental
    Micafungin

    Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour. Micafungin will be administered for a minimum of 14 days until 1 of the following conditions applied: •Negative results (absence of Candida growth) from at least 2 consecutive blood cultures and/or resolution of clinical and laboratory symptoms and reduction of mannan antigen blood level (\< 125 pg/mL) are obtained. •In case of meningitis, hydrocephalus and external ventricular derivation, negative results (absence of Candida growth) from at least 2 consecutive cerebral spinal fluid (CSF) cultures associated with resolution of clinical and laboratory symptoms. •Interruption (including addition or switch to another antifungal agent or dosage change of micafungin) due to demonstration of therapy failure.

    Drug: Micafungin

Interventions

  • DrugMicafungin

    Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour.

    Also known as: Mycamine

05

What researchers measure

Primary outcomes

  1. Concentration of Micafungin in Blood

    Concentration will be determined from the pharmacokinetic (PK) blood samples collected via capillary micro-method (draws from the heel).

    Time frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10

  2. Concentration of Micafungin in Cerebral Spinal Fluid (CSF)

    Concentration will be determined from the from the CSF samples collected.

    Time frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10

Secondary outcomes

  1. Percentage of Participants with a Response at End of Treatment (EOT) - Success of Therapy (SOT)

    For systemic candidiasis (SC) participants, SOT will be determined by survival associated with negative Candida test results of 2 consecutive blood cultures, completed at start of treatment, or resolution of clinical \& laboratory symptoms together with reduction of mannan antigen blood level (MABL) (\<125 pg/ml). For Candida meningitis (CM), SOT will be determined by survival associated with negative Candida test results of at least 2 consecutive CSF cultures, completed at start of treatment and resolution of clinical and lab symptoms. For hydrocephalus due to Candida infection (CI) and/or external ventricular derivation (EVD), SOT will be determined by survival associated with negative Candida test results of at least 2 consecutive CSF cultures, completed at start of treatment.

    Time frame: Up to day 14

  2. Percentage of Participants with A Response at EOT - Failure of Therapy (FOT)

    For SC participants, FOT will be determined by death due to Candida sepsis, by confirmation of persistence of positive Candida test results from 1 blood culture completed by need to add/switch to another antifungal agent (AA) and/or change of micafungin dose for resolution of infection at any time or by the persistence of Candida colonization in different indicated sites associated with persistence of clinical and lab symptoms and with high (MABL) (≥ 125 pg/ml). For CM, FOT will be determined by death due to CM, by persistence of CI from confirmation of positive CSF culture or by need to add/switch to another AA or dose change of micafungin for resolution of CI at any time. For hydrocephalus due to CI and/or EVD, FOT will be determined by death due to CI, by need to add/switch to another AA or dose change of micafungin for resolution of CI at any time or by persistence of CI from confirmation of positive CSF culture.

    Time frame: Up to day 14

  3. Number of Participants with Adverse Events (AEs)

    An adverse event (AE) will be defined as any untoward medical occurrence in a participant administered a study drug or who will undergo study procedures which may not necessarily have a causal relationship with this treatment. This includes abnormal laboratory tests, vital signs, electrocardiogram data or physical examinations that are defined as AEs if the abnormality will induce clinical signs or symptoms, require active intervention, interruption or discontinuation of study drug or may be clinically significant in the investigator's opinion. The following standard with 3 grades will be used to measure the severity of AEs, including abnormal clinical laboratory values: ● Mild: No disruption of normal daily activities ● Moderate: Affected normal daily activities ● Severe: Inability to perform daily activities. A treatment-emergent adverse event (TEAE) will be defined as an AE observed after starting administration of the test drug/comparative drug.

    Time frame: From the first dose of study drug administration up 72 hours after the last dose, up to 17 days

  4. Comparison of Capillary and Venous Plasma Concentrations of Micafungin

    Micafungin concentrations will be determined from the PK blood samples collected via both capillary micro-method (draws from the heel) and venous methods.

    Time frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10

06

Study locations

2 sites
  • Site IT39001
    Rome, 00146, Italy
  • Site IT39002
    Rome, 00186, Italy
07

References and documents

Publications

  • Auriti C, Goffredo BM, Ronchetti MP, Piersigilli F, Cairoli S, Bersani I, Dotta A, Bagolan P, Pai MP. High-Dose Micafungin in Neonates and Young Infants with Invasive Candidiasis: Results of a Phase 2 Study. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02494-20. doi: 10.1128/AAC.02494-20. Print 2021 Mar 18. PubMed 33558294 ↗

Individual participant data

Plan to share: No — Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

08

Registry details

Key details

Study ID
NCT03421002
Lead sponsor
Astellas Pharma Global Development, Inc.
Collaborators
IRCCS, Ospedale Pediatrico Bambino Gesu
Responsible party
Sponsor
First posted
Feb 5, 2018
Start date
May 30, 2015
Primary completion
Apr 10, 2018
Completion
Apr 10, 2018
Last update
Nov 18, 2024

Study contacts

Executive Medical Director
study director · Astellas Pharma Global Development, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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