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

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

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).

Study Overview

• Status: Completed
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Drug: Posaconazole IV; Drug: Posaconazole tablet; Drug: Posaconazole PFS

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-Capitale, Region De
    • Brussels, Bruxelles-Capitale, Region De, Belgium, 1200
      • UCL St Luc ( Site 1000)
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent ( Site 1002)
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • UZ Leuven ( Site 1001)
• Greece
  • Thessaloniki, Greece, 546 42
    • General Hospital of Thessaloniki "Ippokrateio" ( Site 1050)
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • Athens Childrens Hospital Aglaia Kyriakou ( Site 1052)
  • Kentriki Makedonia
    • Thessaloniki, Kentriki Makedonia, Greece, 546 36
      • University General Hospital of Thessaloniki "AHEPA" ( Site 1053)
• Hungary
  • Budapest, Hungary, 1089
    • Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 1103)
  • Budapest, Hungary, 1097
    • Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet ( Site 1102)
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3526
      • BAZ Megyei Korhaz. Klinikai Onkologia es Sugarterapias Centrum ( Site 1101)
• Israel
  • Haifa, Israel, 3525408
    • Rambam Medical Center ( Site 1125)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Karem Hebrew University Medical Center ( Site 1127)
  • Ramat Gan, Israel, 5262100
    • Chaim Sheba Medical Center ( Site 1126)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 1128)
• Italy
  • Torino, Italy, 10126
    • Ospedale Regina Margherita ( Site 1150)
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata ( Site 1151)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 1326)
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 1325)
• Mexico
  • Mexico City, Mexico, 04530
    • Instituto Nacional de Pediatria ( Site 1200)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"-Infectologia ( Site 1204)
• Peru
  • Lima, Peru, 15038
    • Instituto Nacional de Enfermedades Neoplásicas ( Site 1251)
  • Lima, Peru, 15072
    • Hospital Nacional Edgardo Rebagliati Martins ( Site 1250)
• Russian Federation
  • Leningradskaya Oblast
    • Saint Petersburg, Leningradskaya Oblast, Russian Federation, 197341
      • Almazov National Medical Research Centre ( Site 1284)
  • Moskva
    • Moscow, Moskva, Russian Federation, 117198
      • Dmitry Rogachev National Research Center ( Site 1275)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 194291
      • Institute of Invasive Mycosis ( Site 1282)
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197022
      • Institute of Child Hematology and Transpl n.a.R.M.Gorbacheva ( Site 1281)
• United States
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County ( Site 1409)
    • San Diego, California, United States, 92123
      • Rady Children's Hospital-San Diego ( Site 1401)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1402)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University ( Site 1403)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a diagnosis of possible, probable, or proven IA per modified 2008/2020 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
• 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 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 or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Posaconazole; 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; Posaconazole (POS) 6 mg/kg body weight by IV infusion; Other Names: SCH 056592; MK-5592; Noxafil®; Drug: Posaconazole tablet; POS tablet 300 mg taken orally; Other Names: SCH 056592; MK-5592; Noxafil®; Drug: Posaconazole PFS; Dosing based on weight-band taken orally; Other Names: SCH 056592; MK-5592; Noxafil®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experience One or More Treatment-related Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Treatment-related AEs were determined by the investigator to be related to the drug. The 95% confidence interval (CI) was based on the exact binomial method by Clopper- Pearson.	Up to 14 days after treatment (up to Day 102)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Have a Favorable Global Clinical Response Through Week 6	A global clinical response is assessed by the investigator as favorable if the participant is alive and has a complete response (CR) or partial response (PR). CR is defined as survival within the prespecified period of observation, resolution of all attributable symptoms and signs of disease, resolution of radiological lesion(s), and documented clearance of infected sites that are accessible to repeated sampling. PR is defined as survival within the prespecified period of observation, improvement in attributable symptoms and signs of disease, improvement of radiological lesion(s), and evidence of clearance of infected sites that are accessible to repeated sampling.	Up to week 6
Percentage of Participants Who Have a Favorable Global Clinical Response Through Week 12	A global clinical response is assessed by the investigator as favorable if the participant is alive and has a complete response (CR) or partial response (PR). CR is defined as survival within the prespecified period of observation, resolution of all attributable symptoms and signs of disease, resolution of radiological lesion(s), and documented clearance of infected sites that are accessible to repeated sampling. PR is defined as survival within the prespecified period of observation, improvement in attributable symptoms and signs of disease, improvement of radiological lesion(s), and evidence of clearance of infected sites that are accessible to repeated sampling.	Up to Week 12
Percentage of Participants Who Have a Relapse of Invasive Aspergillosis (IA) at Any Point After Achieving Favorable Global Clinical Response	In participants who achieved favorable global clinical response, relapse of IA is defined as the re-emergence of clinical, radiographic, or other relevant abnormalities indicating IA.	Up to 28 days post-treatment (up to Day 116)
Average Plasma Concentration (Cavg) of POS by Age Cohorts	Steady state Cavg was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 Cavg parameter values (1 for IV dosing, 1 for oral dosing).	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Minimum Plasma Concentration (Cmin) of POS by Age Cohorts	Steady state Cmin was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 Cmin parameter values (1 for IV dosing, 1 for oral dosing).	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Maximum Plasma Concentration (Cmax) of POS by Age Cohorts	Steady state Cmax was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 Cmax parameter values (1 for IV dosing, 1 for oral dosing).	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Area Under the Concentration Time Curve Over the Dosing Interval (AUCtau) of POS by Age Cohorts	Steady state AUCtau was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 AUCtau parameter values (1 for IV dosing, 1 for oral dosing).	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Time to Reach Cmax (Tmax) of POS by Age Cohorts	Steady state Tmax was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 Tmax parameter values (1 for IV dosing, 1 for oral dosing).	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Average Plasma Concentration (Cavg) of POS by Formulation	Steady-state Cavg was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N > 2.	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Minimum Plasma Concentration (Cmin) of POS by Formulation	Steady-state Cmin was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N > 2.	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Maximum Plasma Concentration (Cmax) of POS by Formulation	Steady-state Cmax was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N > 2.	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Area Under the Concentration Time Curve Over the Dosing Interval (AUCtau) of POS by Formulation	Steady-state AUCtau was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N > 2.	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Time to Reach Cmax (Tmax) of POS by Formulation	Steady-state Tmax was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N > 2.	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Percentage of Participants With Different Categories of Palatability After First Day of Treatment With the POS PFS Formulation	Palatability was categorized on the first day (Day 8) on PFS based on responses by participants to a palatability questionnaire. Per protocol participants were pooled into a single treatment group. Palatability categories for taste are as follows: Very good; Good; Very bad; Neither good nor bad.	First day of PFS treatment (Day 8)
Percentage of Participants With Different Categories of Palatability After Last Day of Treatment With the POS PFS Formulation	Palatability was categorized on the last day (Day 85) on PFS based on responses by participants to a palatability questionnaire. Per protocol participants were pooled into a single treatment group Palatability categories for taste are as follows: Very good; Good; Very bad; Neither good nor bad.	Last day of PFS treatment (Day 85)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2020
• Primary Completion (Actual): December 18, 2023
• Study Completion (Actual): December 18, 2023

Study Registration Dates

• First Submitted: January 3, 2020
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Aspergillosis; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: 5592-104; MK-5592-104 (Other Identifier: MSD); 2019-002267-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No