Posaconazole (MK-5592) IV and oral in children less than 2 years of age with invasive fungal infectio

Phase 1

• Conditions: Invasive Fungal Infection; MedDRA version: 20.0Level: PTClassification code 10017533Term: Fungal infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2019-003842-34-BE
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-11-23
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

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-a 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified