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

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.

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.

Study Overview

• Status: Terminated
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Drug: Voriconazole

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital, Pediatric Oncology Office
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno
  • Brno, Czechia, 62500
    • Fakultni nemocnice Brno
• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • UMC St. Radboud
• Poland
  • Wroclaw, Poland, 50-345
    • Klinika Transplantacji Szpiku, Onkologii i Hematologii Dzieciecej
• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hospital
  • Singapore, Singapore, 119074
    • National University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall d'Hebron
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron. Servicio de Farmacia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28041
    • HOSPITAL UNIVERSITARIO 12 DE OCTUBRE Servicio de Farmacia
• Thailand
  • Bangkok
    • Bangkok noi, Bangkok, Thailand, 10700
      • Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University
    • Patumwan, Bangkok, Thailand, 10330
      • Department of Pediatrics, Faculty of Medicine, Chulalongkorn University
    • Rajathevee, Bangkok, Thailand, 10400
      • Department of Pediatrics, Phramongkutklao hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center Oakland (CHRCO)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23298
      • Pediatric Hematology and Oncology, Virginia Commonwealth University Health System
    • Richmond, Virginia, United States, 23219
      • Children's Pavilion, Virginia Commonwealth University Health System
    • Richmond, Virginia, United States, 23298-0042
      • Virginia Commonwealth University Health System, Hospital Pharmacy
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/MCV Clinical Pathology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Martin JM, Macias-Parra M, Mudry P, Conte U, Yan JL, Liu P, Capparella MR, Aram JA. Safety, Efficacy, and Exposure-Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis. Pediatr Infect Dis J. 2017 Jan;36(1):e1-e13. doi: 10.1097/INF.0000000000001339.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2009
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: February 3, 2009
• First Submitted That Met QC Criteria: February 3, 2009
• First Posted (Estimate): February 4, 2009

Study Record Updates

• Last Update Posted (Actual): June 16, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Pediatrics voriconazole invasive fungal infection invasive aspergillosis immunocompromized
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Aspergillosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Voriconazole
• Other Study ID Numbers: A1501080; 2008-005275-10 (EudraCT Number)