| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| invasive candidiasis, including candidemia (ICC) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10064954 |
| E.1.2 | Term | Invasive candidiasis |
|
| 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 assess the safety and tolerability of anidulafungin when used to treat children with invasive candidiasis, including candidemia. |
|
| E.2.2 | Secondary objectives of the trial |
| . To assess the efficacy of anidulafungin, as measured by global response, at the following time points: EOIVT, EOT, 2-week FU visit and 6-week FU visit; To explore pharmacokinetic parameters of anidulafungin in children aged 1 month to <2 years following IV infusion of anidulafungin (area under curve over dosing interval (AUC24) and peak concentration (Cmax)); To explore the exposure-response (safety and efficacy endpoints) relationship of anidulafungin using a nonlinear mixed effects approach as appropriate, including exploring the association between PK-PD index (eg, AUC/MIC) and efficacy endpoints; To assess rates of relapse at the Week 2 and Week 6 FU visits; To assess rates of new infection at the Week 2 and Week 6 FU visits; To assess all-cause mortality during study therapy and FU visits. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Diagnosis of ICC from a blood culture or a culture of a specimen from a normally sterile site taken within 96 hours before study entry. Diagnosis will be based on presence of at least one of the following: Candidemia: at least one blood culture positive for yeast (in the absence of other demonstrated foci of infection) or; Other forms of invasive candidiasis: positive culture for yeast from a specimen from a normally sterile site with or without a positive blood culture; positive yeast culture from a newly-placed drain in a normally sterile site; or any positive blood culture for yeast plus ophthalmic examination consistent with Candida endophthalmitis. NOTE: Positive yeast cultures from sputum (including those obtained by bronchoalveolar lavage or an endotracheal aspirate) will not qualify as a positive culture. AND At least one of the following: A fever defined as an oral/tympanic temperature &#8805;100.4F (38.0C), rectal temperature &#8805;101.4F (38.6C) or an axillary temperature &#8805;99.4F (37.4C); Hypothermia defined as a temperature less than 96.8F (36.0C); A systolic blood pressure of less than 100% for age and gender norms (per National High Blood Pressure Education Program (NHBPEP) Working Group on Children and Adolescents guidelines5); Signs or symptoms of candidemia/invasive candidiasis which may include the following: feeding intolerance, bloody stools, abdominal distension, thrombocytopenia, lethargy, color change, hyperglycemia, glycosuria, unexplained metabolic acidosis.2. Male or female between the ages of 1 month and <18 years. Females of childbearing potential must have adequate contraception as determined by the Investigator for the duration of the trial. 3. For each subject, parent or legal guardian must be willing and able to provide signed and dated written informed consent documentation. Assent from the child or adolescent will be obtained as appropriate. This is to be obtained prior to enrollment. 4. Will be available for the duration of the study and be able to abide by the study restrictions. |
|
| E.4 | Principal exclusion criteria |
| 1. Premature neonates born at gestation of less than 36 weeks (unless the sum of gestational age plus chronological age is at least 44 weeks). Note: Rounding to the closest week is round up one week if birth occurred on days 4 to 6 of the week and round down one week if birth occurred on days 1 to 3 of the week. 2. Known history of allergy, hypersensitivity or serious reaction to echinocandin antifungals. 3. Female subjects who are pregnant or lactating, or planning a pregnancy during the course of the study. 4. Subjects who have received more than 48 hours of systemic antifungal therapy for the Candida infection for which their enrollment is being considered. 5. Subjects who have failed antifungal therapy with any systemic antifungal for this episode of candidiasis/candidemia. Recurrence within 2 weeks is considered failure of previous therapy. 6. Subjects with any of the following abnormal laboratory values: Total bilirubin, AST or ALT >5 times the upper limit of normal (ULN). 7. Subjects who require continued treatment with another systemic antifungal agent [oral nonabsorbable azoles (eg, clotrimazole troches) will be permitted]. Exception: the first 6 subjects enrolled who are between 1 month to <2 years of age may receive a second systemic antifungal agent at the investigator’s discretion. 8. Subjects with poor venous access that would preclude IV drug delivery or multiple blood draws.9. Subjects who have participated in a study of an investigational drug or device (without any FDA and EMEA approved indications) within four weeks of study entry. The investigational use of licensed agents are permitted if the subject is on a stable regimen for four weeks prior to study start, and expected to remain on the stable regimen for the duration of the trial. 10. Life expectancy <72 hours. 11. Subjects with suspected Candida osteomyelitis, endocarditis, or meningitis. 12. Subjects with prosthetic devices at a suspected site of infection are to be excluded, unless the device is removed at study entry. [Hemodialysis shunts (AV fistulae) may remain in situ).] 13. Subjects with a prosthetic heart valve or vascular graft suspected to be the site of the Candida infection and positive blood cultures. 14. Other severe acute or chronic medical or psychiatric condition, electrocardiogram (ECG) abnormalities, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint will be an assessment of the safety and tolerability of anidulafungin. |
|
| 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 | No |
| 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 | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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