Clinical trial NCT04218851: Posaconazole (MK-5592) Intravenous and Oral in Children With Invasive Aspergillosis (IA) (MK-5592-104)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Invasive Aspergillosis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-01-06
Enrollment: 31
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Experience One or More Treatment-related Adverse Events (AEs)
timeFrame: Up to 14 days after treatment (up to Day 102)
Secondary outcomes:
measure: Percentage of Participants Who Have a Favorable Global Clinical Response Through Week 6
timeFrame: Up to week 6
measure: Percentage of Participants Who Have a Favorable Global Clinical Response Through Week 12
timeFrame: Up to Week 12
measure: Percentage of Participants Who Have a Relapse of Invasive Aspergillosis (IA) at Any Point After Achieving Favorable Global Clinical Response
timeFrame: Up to 28 days post-treatment (up to Day 116)
measure: Average Plasma Concentration (Cavg) of POS by Age Cohorts
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Minimum Plasma Concentration (Cmin) of POS by Age Cohorts
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Maximum Plasma Concentration (Cmax) of POS by Age Cohorts
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Area Under the Concentration Time Curve Over the Dosing Interval (AUCtau) of POS by Age Cohorts
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Time to Reach Cmax (Tmax) of POS by Age Cohorts
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Average Plasma Concentration (Cavg) of POS by Formulation
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Minimum Plasma Concentration (Cmin) of POS by Formulation
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Maximum Plasma Concentration (Cmax) of POS by Formulation
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Area Under the Concentration Time Curve Over the Dosing Interval (AUCtau) of POS by Formulation
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Time to Reach Cmax (Tmax) of POS by Formulation
timeFrame: Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
measure: Percentage of Participants With Different Categories of Palatability After First Day of Treatment With the POS PFS Formulation
timeFrame: First day of PFS treatment (Day 8)
measure: Percentage of Participants With Different Categories of Palatability After Last Day of Treatment With the POS PFS Formulation
timeFrame: Last day of PFS treatment (Day 85)
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County ( Site 1409)
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital-San Diego ( Site 1401)
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1402)
state: Illinois
city: Saint Louis
country: United States
facility: Washington University ( Site 1403)
state: Missouri
city: Brussels
country: Belgium
facility: UCL St Luc ( Site 1000)
state: Bruxelles-Capitale, Region De
city: Gent
country: Belgium
facility: UZ Gent ( Site 1002)
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven ( Site 1001)
state: Vlaams-Brabant
city: Athens
country: Greece
facility: Athens Childrens Hospital Aglaia Kyriakou ( Site 1052)
state: Attiki
city: Thessaloniki
country: Greece
facility: University General Hospital of Thessaloniki "AHEPA" ( Site 1053)
state: Kentriki Makedonia
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "Ippokrateio" ( Site 1050)
city: Miskolc
country: Hungary
facility: BAZ Megyei Korhaz. Klinikai Onkologia es Sugarterapias Centrum ( Site 1101)
state: Borsod-Abauj-Zemplen
city: Budapest
country: Hungary
facility: Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 1103)
city: Budapest
country: Hungary
facility: Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet ( Site 1102)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 1125)
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hebrew University Medical Center ( Site 1127)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 1126)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1128)
city: Torino
country: Italy
facility: Ospedale Regina Margherita ( Site 1150)
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata ( Site 1151)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 1326)
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 1325)
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"-Infectologia ( Site 1204)
state: Nuevo Leon
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria ( Site 1200)
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplásicas ( Site 1251)
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins ( Site 1250)
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre ( Site 1284)
state: Leningradskaya Oblast
city: Moscow
country: Russian Federation
facility: Dmitry Rogachev National Research Center ( Site 1275)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Institute of Invasive Mycosis ( Site 1282)
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Institute of Child Hematology and Transpl n.a.R.M.Gorbacheva ( Site 1281)
state: Sankt-Peterburg
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: