Posaconazole (MK-5592) Intravenous and Oral in Children With Invasive Aspergillosis (IA) (MK-5592-104)

Study Overview
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Brief Summary
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This study will evaluate the safety, efficacy, and pharmacokinetics of posaconazole (POS) intravenous (IV) and oral formulations in pediatric participants 2 to <18 years of age with invasive aspergillosis (IA).

Official Title
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A Phase 2, Open-Label, Non-Comparative Clinical Trial to Study the Safety and Efficacy of Posaconazole (POS, MK-5592) in Pediatric Participants Aged 2 to Less Than 18 Years With Invasive Aspergillosis

Conditions
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Invasive Aspergillosis

Intervention / Treatment
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* Drug: Posaconazole IV
* Drug: Posaconazole PFS
* Drug: Posaconazole tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a diagnosis of possible, probable, or proven IA per modified 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) disease definitions Has one or more of pre-defined risks as per modified 2008 EORTC/MSG disease definitions Meets pre-defined mycologic and clinical criteria as per modified 2008 EORTC/MSG disease definitions Has demonstrated fungal elements (by cytology or microscopy) or positive culture for Aspergillus obtained by sterile sampling of disease tissue as per modified EORTC/MSG disease definitions Has a central line (e.g., central venous catheter, peripherally-inserted central catheter) in place or planned to be in place prior to beginning IV study treatment. Has clinical symptoms consistent with an acute episode of IA, defined as duration of clinical syndrome of <30 days. Participants weigh at least 10 kg, and may be of any race/ethnicity. During the intervention period and for at least 30 days after the last dose of study treatment, males agree to be abstinent from heterosexual intercourse or use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause). Female is is not pregnant or breastfeeding, and is not a woman of child bearing potential (WOCBP) or is a WOCBP using a highly effective contraceptive method. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. Exclusion Criteria: Has chronic (≥30 days' duration) IA, relapsed/recurrent IA, or refractory IA that has not responded to prior antifungal treatment. Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis. Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study treatment used. 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 time of first dose of study treatment. Has known hereditary fructose intolerance. Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. Is on artificial ventilation at the time of first dose of study treatment. Has received any treatment prohibited by the protocol. Has enrolled previously in the current study and been discontinued. Is not expected, in the opinion of the investigator, to survive for at least 1 month after the initiation of study treatment.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Posaconazole<br>On Day 1 participants receive 2 administrations of posaconazole (POS) 6 mg/kg body weight by intravenous (IV) infusion. On Days 2 through 7, participants receive POS 6 mg/kg body weight once daily by IV infusion. Beginning at Day 8 up to Day 84, participants may transition to receiving an oral formulation, or they may remain on the IV formulation. | Drug: Posaconazole IV<br>* Posaconazole (POS) 6 mg/kg body weight by IV infusion<br>* Other names: Noxafil®;Drug: Posaconazole PFS<br>* POS PFS 6 mg/kg body weight taken orally<br>* Other names: Noxafil®;Drug: Posaconazole tablet<br>* POS tablet 300 mg taken orally<br>* Other names: Noxafil®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with Treatment Related Adverse Events (AEs) | Percentage of participants who experience one or more treatment-related adverse events (AEs) | Up to 14 days after treatment (up to Day 100) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with a favorable global clinical response | Percentage of participants who have a favorable global clinical response | Up to End of Trial (EOT) visit (up to Day 87) | 
| Participants who have a relapse of invasive aspergillosis (IA) | Percentage of participants who have a relapse of invasive aspergillosis (IA) at any point after achieving favorable global clinical response | Up to 28 days post-treatment (up to Day 114) | 
| Average plasma concentration (Cavg) of Posaconazole (POS) | Average plasma concentration (Cavg) of Posaconazole (POS) | Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 | 
| Minimum plasma concentration (Cmin) of POS | Minimum plasma concentration (Cmin) of POS | Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 | 
| Maximum plasma concentration (Cmax) of POS | Maximum plasma concentration (Cmax) of POS | Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 | 
| Area under the concentration-time curve (AUC) of POS | Area under the concentration-time curve (AUC) of POS | Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 | 
| Time to reach Cmax (Tmax) of POS | Time to reach Cmax (Tmax) of POS | Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 | 
| Participants with different categories of palatability | Percentage of participants with different categories of palatability after treatment with the POS PFS formulation | Day 8 and Day 84 |