A Study To Evaluate The Safety Of Voriconazole As Treatment Of Invasive Aspergillosis (Fungal Infection) And Other Rare Molds In Children

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety profile of voriconazole (an antifungal drug) when used in children who have invasive aspergillosis (IA) and other rare systemic fungal infections.

Official Title
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A Prospective, Open-label, Non-randomized, Multi-center Study To Investigate The Safety And Tolerability Of Voriconazole As Primary Therapy For Treatment Of Invasive Aspergillosis And Molds Such As Scedosporium Or Fusarium Species In Pediatric Patients.

Conditions
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Invasive Aspergillosis

Intervention / Treatment
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* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Immunocompromised with clinically compatible illness. Diagnosis of proven or probable or possible Invasive Aspergillosis (based on a modified version of the revised EORTC/MSG consensus definitions). Diagnosis of infection due to Scedosporium or Fusarium species. Male and female from 2 to 17 years of age. Females with childbearing potential must have negative pregnancy test and be using appropriate contraception. Exclusion Criteria: Allergy or hypersensitivity to the azole drugs. Female subjects who are pregnant or lactating. Patients who received more than four days of antifungal drugs to treat the current episode of invasive aspergillosis or rare mold infection. Received within 24 hours prior to enrollment drugs that may cause QT interval prolongation. Significant liver, kidney or heart dysfunction. Not expected to survive for at least 5 days.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 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
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Children from 2 to 17 years who have possible, probable or proven invasive aspergillosis, or other rare mold infection (eg, Scedosporium and Fusarium). | Drug: Voriconazole<br>* All subjects will receive voriconazole for a minimum of 6 weeks and a maximum of 12 weeks. All subjects must receive intravenous (IV) voriconazole for the first week of therapy. Group 1: Subjects 2 to 11 years old and subjects 12 to 14 years old with low body weight (<50 kg) will receive 9 mg/kg IV every 12 hours (q12h) on day 1, then 8 mg/kg IV q12h starting day 2. If there is a significant clinical improvement after the first week of IV therapy, subjects may be switched to the step-down oral regimen (9 mg/kg PO q12h with a maximum dose of 350 mg PO q12h) at the discretion of the investigator. Group 2: Subjects 12 to 17 years old (excluding 12-14-year-olds weighing <50 kg) will receive 6 mg/kg IV q12h on day 1, then 4 mg/kg IV q12h starting day 2. Similar to Group 1, subjects may be switched to the step-down oral regimen (200 mg PO q12h) at the discretion of the investigator. Oral voriconazole can be administered as tablet or oral suspension.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) |  | Baseline, daily while hospitalized, Days 7, 14, 28, 42, 84, and 114, at end of treatment, and up to 1 month post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Global Response of Success | Percentage of participants with global response of success at Weeks 6 and at EOT (up to Week 12). Global response of success was defined as a participant who achieved a complete or partial global response per the investigator. Complete response was defined as resolution of all clinical signs and symptoms PLUS resolution of 90 percent (%) or more of the lesions visible on radiological studies and attributed to invasive aspergillosis (IA) at Baseline. Partial response was defined as clinical improvement PLUS 50% to <90% resolution of the radiological lesions attributed to IA at Baseline. | Weeks 6 and End of Treatment (EOT; up to Week 12) | 
| All-Cause Mortality - Number of Participant Deaths | Number of participant deaths reported at Week 6 and at EOT (up to Week 12). | Week 6 and EOT (up to Week 12) | 
| Attributable Mortality - Number of Participant Deaths | Number of participant deaths attributable to study drug reported at Week 6 and at EOT (up to Week 12). | Weeks 6 and EOT (up to Week 12) | 
| Time to Death |  | Baseline up to 1 month post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatrics voriconazole invasive fungal infection invasive aspergillosis immunocompromized