E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Fungal infection in the neonate |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy and safety of Micafungin in comparison to amphotericin B deoxycholate (CAB) in the treatment of proven neonatal candidiasis
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E.2.2 | Secondary objectives of the trial |
To further evaluate the pharmacokinetics of micafungin as well as CAB in this patient population |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
In the United States of America, billing information and data on length of stay will be obtained from each infant’s hospitalization during the study for a health economic assessment for those infants where consent is specifically obtained. |
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E.3 | Principal inclusion criteria |
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Infant greater than 48 hours of life up to DOL 120 at the time of culture acquisition.
3. Diagnosis of invasive candidiasis by one of the following (see Appendix 1 for Site-Specific Diagnostic Criteria):
a. Proven Candidemia: One positive blood culture collected within 4 days prior to the first dose of study drug.
b. Proven Candiduria: One positive urine fungal culture obtained within 4 days prior to the first dose of study drug by I/O catheterization or suprapubic aspiration. A fungal culture obtained from an indwelling catheter is acceptable only if the culture was obtained at the time the catheter was placed. Positive fungal culture must show greater than or equal to 1000 CFU/mL in a single urine culture collected via I/O catheterization or greater than or equal to 100 CFU/mL in a single urine culture collected via suprapubic aspiration.
c. Proven Candida Meningitis: The presence of Candida species in CSF culture obtained within +/- 4 days from the first dose of study drug.
d. Candida – Other focus:
i. Positive tissue biopsy or positive culture from a normally sterile body fluid obtained within 4 days prior to the first dose of study drug, or
ii. Positive culture for Candida (or yeast) that was taken from a new drain either at the time of drain placement or within 24 hours after placement from a normally sterile site. The drain must have been placed within 7 days prior to the first dose of study drug. NB: Culture results to confirm Candida species may be pending at the time of enrollment if the following criteria are met:
- For candidemia, staining/microscopy of the blood culture sample reveals preliminary evidence of yeast.
- For invasive candidiasis other than candidemia, histology/cytology reveals findings consistent with yeast.
NB: All Candida organisms must be speciated.
4. Infant must have sufficient venous access to permit administration of study medication and monitoring of safety variables.
5. Subject's parent or legal guardian agrees not to allow subject to participate in another study with another investigational drug while on treatment.
NB: Waivers to the inclusion criteria will NOT be allowed. |
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E.4 | Principal exclusion criteria |
Subject will be excluded from participation if any of the following apply:
1. Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or systemic amphotericin B product.
2. Infant who has received more than 48 hours of systemic antifungal therapy prior to the first dose of study drug for treatment of the current Candida infection. Cumulative doses must not exceed 2 mg/kg of CAB. For systemic antifungal therapy not specifically stated here,
infants with more than 2 therapeutic daily doses within the 48 hours prior to the first dose of study drug will not be eligible.
3. Infant who has a breakthrough systemic fungal infection while receiving an amphotericin B product or an echinocandin as prophylaxis.
NB: Infants with a breakthrough fungal infection while receiving azole prophylaxis will be eligible for enrollment.
4. Infant who has failed prior systemic antifungal therapy for this episode of invasive candidiasis, including recurrence of the same Candida infection within 2 weeks of completing systemic antifungal therapy.
5. Infant with a concomitant medical condition, whose participation, in the opinion of the Investigator and/or medical advisor, may create an unacceptable additional risk.
6. Infant previously enrolled in this study.
7. Infant who is co-infected with a non-Candida fungal organism.
8. Infant whose positive yeast cultures are solely from an indwelling bladder catheter (unless obtained at the time the indwelling catheter was placed) or sputum.
NB: Waivers to the exclusion criteria will NOT be allowed. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is fungal free survival at one week following the last dose of study drug.
Fungal free survival is defined as alive at one week following the last dose of study drug and eradication (fungal free) with no requirement for alternative systemic antifungal therapy for continued treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
One week following the last dose of study drug |
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E.5.2 | Secondary end point(s) |
- Time to mycological clearance of invasive candidiasis.
- Fungal free survival in infants with end-organ dissemination at end of
study drug therapy and one week after last dose of study drug.
- Overall incidence of emergent and recurrent fungal infections through the end of study.
- Time to positive clinical response (complete or partial).
- Clinical response (complete, partial, stabilization, progression) at the end of study drug therapy and one week after last dose of study drug.
- Mycological response at end of study drug therapy and one week after
last dose of study drug.
- Status of follow-up imaging and exams (improved, stable, worse) for
infants with end-organ assessments.
- Model parameters such as clearance and volume of distribution. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At end of study drug therapy and/or one week after last dose of study drug. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
Greece |
Croatia |
Romania |
Argentina |
Brazil |
Chile |
Colombia |
Ecuador |
Hungary |
Lebanon |
Spain |
Thailand |
Israel |
Mexico |
Peru |
Philippines |
South Africa |
Taiwan |
Turkey |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |