Posaconazole (MK-5592) IV and oral in children (less than 2 years) with IFI

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

28 Apr 2021 → ongoing

Decision date (initial)

2024-04-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-505613-24-00

EudraCT number

2019-003842-34

ClinicalTrials.gov

NCT04665037

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety

To estimate the pharmacokinetics (PK) of posaconazole (POS) intravenous (IV) and powder for oral suspension (PFS) in participants <2 years of age (Panels A and B).

Secondary objectives 4

1. To compare the exposures to POS in neonates and infants <2 years of age to those from adult and older pediatric population (Panel B only).
2. To evaluate the safety and tolerability of POS in participants <2 years of age (Panels A and B separately).
3. To evaluate all-cause mortality at Day 28 in participants treated with POS (Panel B only).
4. To evaluate the need for additional antifungal therapy (Panel B only)

Conditions and MedDRA coding

Fungal infection

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000468-PIP02-12

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Panel A: Is undergoing treatment for possible, probable, or proven invasive fungal infection (IFI) known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (which can include candidiasis)
2. Panel B: has an investigator-assessed diagnosis of possible, probable, or proven IFI known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (and cannot include candidiasis)
3. Has a central line (eg, central venous catheter, peripherally-inserted central catheter) in place or planned to be in place before beginning IV study intervention
4. Has a body weight of ≥500 g
5. The participant (or legally acceptable representative) has provided documented informed consent for the study.

Exclusion criteria 13

1. Has received POS within 30 days before Day 1
2. Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
3. Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
4. Has known or suspected active COVID-19 infection
5. Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study intervention used
6. Has any known history of torsade de pointes, unstable cardiac arrhythmia or proarrhythmic conditions, a history of recent myocardial infarction, congenital or acquired QT interval (QT) prolongation, or cardiomyopathy in the context of cardiac failure within 90 days of first dose of study intervention
7. Has received any listed prohibited medications within the specified timeframes before the start of study intervention
8. Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (Panel B)
9. Has suspected/proven invasive candidiasis (Panel B)
10. Has enrolled previously in the current study and been discontinued
11. Has QTc prolongation at screening >500 msec
12. Has significant liver dysfunction
13. Is hemodynamically unstable, exhibits hemodynamic compromise, or is not expected to survive at least 5 days

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 14

1. Average concentration (Cavg) of single-dose IV POS (Panel A)
2. Maximum concentration (Cmax) of single-dose IV POS (Panel A)
3. Time to maximum concentration (Tmax) of single-dose IV POS (Panel A)
4. Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A)
5. Clearance (CL) of single-dose IV POS (Panel A)
6. Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A)
7. Cavg of multiple-dose IV POS (Panel B)
8. Cmax of multiple-dose IV POS (Panel B)
9. Tmax of multiple-dose IV POS (Panel B)
10. AUC0-24 of multiple-dose IV POS (Panel B)
11. CL of multiple-dose IV POS (Panel B)
12. Cavg of multiple-dose PFS (Panel B)
13. Cmax of multiple-dose PFS (Panel B)
14. AUC0-24 of multiple-dose PFS (Panel B)

Secondary endpoints 6

1. Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B only)
2. Percentage of participants with ≥1 adverse events (AEs) [Panels A and B]
3. Percentage of participants with ≥1 drug-related AEs (Panels A and B)
4. Percentage of participants discontinuing from study treatment due to AE(s) (Panels A and B)
5. Percentage of participants with all-cause mortality through 28 days (Panel B)
6. Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period [Panel B]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Stephen Holden

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Stephen Holden

Third parties 3

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications