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

Invasive Aspergillosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04218851
• Other study ID #: 5592-104
• Secondary ID: MK-5592-1042019-
• Status: Completed
• Phase: Phase 2
• Start date: July 2, 2020
• Est. completion date: December 18, 2023

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 18, 2023
• Est. primary completion date: December 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aspergillosis
• Invasive Aspergillosis

Intervention

Drug:
• Posaconazole IV
Posaconazole (POS) 6 mg/kg body weight by IV infusion
• Posaconazole PFS
POS PFS 6 mg/kg body weight taken orally
• Posaconazole tablet
POS tablet 300 mg taken orally

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Greece,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Peru,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	Minimum plasma concentration (Cmin) of POS	Minimum plasma concentration (Cmin) of POS	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Secondary	Maximum plasma concentration (Cmax) of POS	Maximum plasma concentration (Cmax) of POS	Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information