E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Invasive Fungal Infection |
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E.1.1.1 | Medical condition in easily understood language |
Invasive Fungal Infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017533 |
E.1.2 | Term | Fungal infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
1. To estimate the pharmacokinetics (PK) of posaconazole (POS) intravenous (IV) and powder for oral suspension (PFS) in participants <2 years of age (Panels A and B). |
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E.2.2 | Secondary objectives of the trial |
1. To compare the exposures to POS in neonates and infants <2 years of age to those from adult and older pediatric population (Panel B only). 2. To evaluate the safety and tolerability of POS in participants <2 years of age (Panels A and B separately). 3. To evaluate all-cause mortality at Day 28 in participants treated with POS (Panel B only). 4. To evaluate the need for additional antifungal therapy (Panel B only).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Panel A Participants Only 1. Is undergoing treatment for possible, probable, or proven IFI known or suspected to be caused by fungal pathogens against which POS has demonstrated activity (which can include candidiasis) per the modified EORTC/MSG consensus criteria Panel B Participants Only 2. Has a diagnosis of possible, probable, or proven IFI known or suspected to be caused by fungal pathogens against which POS has demonstrated activity (and cannot include candidiasis) per the modified 2008 EORTC/MSG consensus criteria Panel A and Panel B Participants 3. If enrolled with a possible or probable IFI diagnosis, has one or more of the following host factors as per the modified 2008 EORTC/MSG consensus criteria: - Recent history of neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3]) within 30 days before screening - Receipt of an allogeneic HSCT - Prolonged use of corticosteroids for >3 weeks (average minimum dose of 0.3 mg/kg/day of prednisone equivalent) - Treatment with other recognized T-cell immune suppressants, including cyclosporine, TNF-α blockers, specific monoclonal antibodies (such as alemtuzumab), or nucleoside analogues during the past 90 days - Inherited severe immunodeficiency (including but not limited to chronic granulomatous disease or severe combined immunodeficiency) 4. If enrolled with a possible or probable IFI diagnosis, meets the following criteria, as per the modified 2008 EORTC/MSG consensus criteria: - Possible IFI includes participants with clinical and host factor criteria. - Probable IFI includes participants with a host factor, a clinical criterion, and a mycological criterion providing evidence of a fungal infection by direct or indirect testing. 5. If enrolled with a proven IFI diagnosis, sampling of normally sterile tissue has shown fungal elements (by cytology or microscopy), or sampling of normally sterile tissue or blood has yielded a positive culture for a fungal pathogen as per the modified 2008 EORTC/MSG consensus criteria 6. Has clinical symptoms consistent with an acute episode of IFI, defined as duration of clinical syndrome of <30 days 7. Has a central line (eg, central venous catheter, peripherally inserted central catheter) in place or planned to be in place before beginning IV study intervention 8. Is male or female, from birth to <2 years of age at the time of first dose of study intervention 9. Has a body weight of ≥500 g 10. The participant (or legally acceptable representative) has provided documented informed consent for the study |
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E.4 | Principal exclusion criteria |
Panel A and B Participants 1. Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis 2. Has known or suspected active COVID-19 infection. 3. Has chronic (≥30 days' duration) IFI, relapsed/recurrent IFI, or refractory IFI that has not responded to prior antifungal treatment 4. Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study intervention used 5. Has any known history of torsade de pointes, unstable cardiac arrhythmia or proarrhythmic conditions, a history of recent myocardial infarction, congenital or acquired QT prolongation, or cardiomyopathy in the context of cardiac failure within 90 days of first dose of study intervention 6. Has known or suspected Gilbert disease 7. Has any condition that, in the opinion of the investigator, may interfere with optimal participation in the study
Panel B Participants Only 8. Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. 9. Has invasive candidiasis.
Panel A Participants Only 10. Has received any treatment specifically listed in the protocol within the specified time period before the start of study intervention
Panel B Participants Only 11.Has received any treatment specifically listed in the protocol within the specified time period before the start of study intervention.
Panel A and Panel B Participants 12. Has enrolled previously in the current study and been discontinued 13. Has QTc prolongation (based on either Fridericia or Bazett's correction) at screening >500 msec 14. Has significant liver dysfunction at screening, defined as: - Total bilirubin >1.5 × ULN and AST or ALT >3 × ULN with normal alkaline phosphatase 15. Has calculated creatinine clearance <20 mL/min/1.73 m2 (modified Schwartz formula) at screening 16. Is hemodynamically unstable, exhibits hemodynamic compromise, or is not expected to survive at least 5 days 17. Has an immediate family member (eg, parent/legal guardian, sibling) who is investigational site or Sponsor staff directly involved with this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Average concentration (Cavg) of single-dose IV POS (Panel A) 2. Maximum concentration (Cmax) of single-dose IV POS (Panel A) 3. Time to maximum concentration (Tmax) of single-dose IV POS (Panel A) 4. Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A) 5. Clearance (CL) of single-dose IV POS (Panel A) 6. Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A) 7. Cavg of multiple-dose IV POS (Panel B) 8. Cmax of multiple-dose IV POS (Panel B) 9. Tmax of multiple-dose IV POS (Panel B) 10. AUC0-24 of multiple-dose IV POS (Panel B) 11. CL of multiple-dose IV POS (Panel B) 12. AUC0-∞ of multiple-dose IV POS (Panel B) 13. Cavg of multiple-dose PFS (Panel B) 14. Cmax of multiple-dose PFS (Panel B) 15. Tmax of multiple-dose PFS (Panel B) 16. AUC0-24 of multiple-dose PFS (Panel B) 17. CL of multiple-dose PFS (Panel B) 18. AUC0-∞ of multiple-dose PFS (Panel B) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Day 1 and Day 2 2. Day 1 and Day 2 3. Day 1 and Day 2 4. Day 1 and Day 2 5. Day 1 and Day 2 6. Day 1 and Day 2 7. Weeks 1, 2, 4, 6, 9, and 12 8. Weeks 1, 2, 4, 6, 9, and 12 9. Weeks 1, 2, 4, 6, 9, and 12 10. Weeks 1, 2, 4, 6, 9, and 12 11. Weeks 1, 2, 4, 6, 9, and 12 12. Weeks 1, 2, 4, 6, 9, and 12 13. Weeks 1, 2, 4, 6, 9, and 12 14. Weeks 1, 2, 4, 6, 9, and 12 15. Weeks 1, 2, 4, 6, 9, and 12 16. Weeks 1, 2, 4, 6, 9, and 12 17. Weeks 1, 2, 4, 6, 9, and 12 18. Weeks 1, 2, 4, 6, 9, and 12 |
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E.5.2 | Secondary end point(s) |
1. Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B only) 2. Percentage of participants with ≥1 adverse events (AEs) (Panels A and B) 3. Percentage of participants with ≥1 drug-related AEs (Panels A and B) 4. Percentage of participants discontinuing from study treatment due to AE(s) (Panels A and B) 5. Percentage of participants with all-cause mortality (Panel B) 6. Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period [Panel B] |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Day 1 and Day 2 2. Up to 98 days 3. Up to 98 days 4. Up to 84 days 5. Up to Day 28 6. Up to 84 days |
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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 | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 15 |
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 |
Peru |
Belgium |
Greece |
Israel |
Poland |
Russian Federation |
United Kingdom |
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 | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |