Clinical Trial Page

Summary
EudraCT Number:2019-003842-34
Sponsor's Protocol Code Number:MK-5592-127
Clinical Trial Type:Outside EU/EEA
Date on which this record was first entered in the EudraCT database:2020-10-15
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED
A. Protocol Information
A.2EudraCT number2019-003842-34
A.3Full title of the trial
A Phase 2, Open-Label, Single-Arm, Sequential-Panel Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Posaconazole (POS, MK-5592) Intravenous and Powder for Oral Suspension Formulations in Pediatric Participants From Birth to <2 Years of Age With Possible, Probable, or Proven Invasive Fungal Infection
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Posaconazole (MK-5592) IV and oral in children <2 years of age with invasive fungal infection
A.3.2Name or abbreviated title of the trial where available
Posaconazole (MK-5592) IV and oral in children (<2 years) with IFI
A.4.1Sponsor's protocol code numberMK-5592-127
A.5.4Other Identifiers
Name:INDNumber:51,316; 75,061; 125,097
A.7Trial is part of a Paediatric Investigation Plan Yes
A.8EMA Decision number of Paediatric Investigation PlanP/101/2020
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
B.1.3.4CountryUnited States
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc
B.4.2CountryUnited States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2Functional name of contact pointRandi Leavitt
B.5.3 Address:
B.5.3.1Street AddressOne Merck Drive P.O. Box 100
B.5.3.2Town/ cityWhitehouse Station, New Jersey
B.5.3.3Post code08889-0100
B.5.3.4CountryUnited States
B.5.4Telephone number+1 267 305-7518
B.5.6E-mailrandi_leavitt@merck.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Noxafil® (posaconazole)
D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNPOSACONAZOLE
D.3.9.3Other descriptive namePOSACONAZOLE
D.3.9.4EV Substance CodeSUB20322
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number18
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product namePosaconazole
D.3.2Product code MK-5592
D.3.4Pharmaceutical form Powder for oral suspension
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNPOSACONAZOLE
D.3.9.2Current sponsor codeMK-5592
D.3.9.3Other descriptive namePOSACONAZOLE
D.3.9.4EV Substance CodeSUB20322
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number30
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Invasive Fungal Infection
E.1.1.1Medical condition in easily understood language
Invasive Fungal Infection
E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10017533
E.1.2Term Fungal infection
E.1.2System Organ Class 10021881 - Infections and infestations
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
1. 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).
E.2.2Secondary objectives of the trial
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).
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
Panel A Participants Only
1. Is undergoing treatment for IFI (and can include candidiasis)

Panel B Participants Only
2. Has a diagnosis of possible, probable, or proven IFI (and cannot include candidiasis) per the modified 2008 EORTC/MSG consensus criteria
3. If enrolled with a possible or probable IFI diagnosis, has one or more of the following risks as per the modified 2008 EORTC/MSG consensus criteria:
- Recent history of neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3]) within 30 days before screening
- Receipt of an allogeneic HSCT
- Prolonged use of corticosteroids for >3 weeks (average minimum dose of 0.3 mg/kg/day of prednisone equivalent)
- Treatment with other recognized T-cell immune suppressants, including cyclosporine, TNF-α blockers, specific monoclonal antibodies (such as alemtuzumab), or nucleoside analogues during the past 90 days
- Inherited severe immunodeficiency (including but not limited to chronic granulomatous disease or severe combined immunodeficiency)
4. If enrolled with a possible or probable IFI diagnosis, meets mycologic and clinical criteria as per the modified 2008 EORTC/MSG consensus criteria:
- Possible IFI includes participants with clinical criteria, with the anticipation that further diagnostic workup is in progress and is anticipated to result in a diagnosis of probable IFI
- Probable IFI includes participants with clinical criteria, along with mycological criteria for mold/yeasts including, evidence of a fungal infection by histology or microscopy, or positive culture for a fungal infection of a specimen taken by nonsterile sampling of an infected site. A probable infection will also include participants with positive fungal serology
5. If enrolled with a proven IFI diagnosis, has shown fungal elements (by cytology or microscopy) or positive culture for a fungal pathogen obtained by sterile sampling of diseased tissue as per the modified 2008 EORTC/MSG consensus criteria
6. Has clinical symptoms consistent with an acute episode of IFI, defined as duration of clinical syndrome of <30 days

Panel A and Panel B Participants
7. 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
8. Is male or female, from birth to <2 years of age at the time of first dose of study intervention
9. Has a body weight of ≥500 g
10. The participant’s legally acceptable representative provides written informed consent for the study
E.4Principal exclusion criteria
Panel B Participants Only
1. Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis
2. Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
3. Is on artificial ventilation or receiving acute CPAP/BPAP at the time of first dose of study intervention
4. Has chronic (≥30 days’ duration) IFI, relapsed/recurrent IFI, or refractory IFI that has not responded to prior antifungal treatment
5. Has invasive candidiasis

Panel A and Panel B Participants
6. Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study intervention used
7. 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 first dose of study intervention
8. Has known or suspected Gilbert disease
9. Has any condition that, in the opinion of the investigator, may interfere with optimal participation in the study

Panel A Participants Only
10. Has received POS within 30 days before Day 1

Panel A and Panel B Participants
11. Has received any treatment specifically listed in the protocol within the specified timeframes before the start of study intervention
12. Has enrolled previously in the current study and been discontinued
13. Has QTc prolongation (based on either Fridericia or Bazett’s correction) at screening >500 msec
14. Has significant liver dysfunction at screening, defined as:
- Total bilirubin >1.5 × ULN and AST or ALT >3 × ULN with normal alkaline phosphatase
or
- ALT or AST >5 × ULN
15. Has calculated creatinine clearance <20 mL/min/1.73 m2 (modified Schwartz formula) at screening
16. Is hemodynamically unstable, exhibits hemodynamic compromise, or is not expected to survive at least 5 days
17. Has an immediate family member (eg, parent/legal guardian, sibling) who is investigational site or Sponsor staff directly involved with this study
E.5 End points
E.5.1Primary end point(s)
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. AUC0-∞ of multiple-dose IV POS (Panel B)
13. Cavg of multiple-dose PFS (Panel B)
14. Cmax of multiple-dose PFS (Panel B)
15. Tmax of multiple-dose PFS (Panel B)
16. AUC0-24 of multiple-dose PFS (Panel B)
17. CL of multiple-dose PFS (Panel B)
18. AUC0-∞ of multiple-dose PFS (Panel B)
E.5.1.1Timepoint(s) of evaluation of this end point
1. Day 1 and Day 2
2. Day 1 and Day 2
3. Day 1 and Day 2
4. Day 1 and Day 2
5. Day 1 and Day 2
6. Day 1 and Day 2
7. Weeks 1, 2, 4, 6, 9, and 12
8. Weeks 1, 2, 4, 6, 9, and 12
9. Weeks 1, 2, 4, 6, 9, and 12
10. Weeks 1, 2, 4, 6, 9, and 12
11. Weeks 1, 2, 4, 6, 9, and 12
12. Weeks 1, 2, 4, 6, 9, and 12
13. Weeks 1, 2, 4, 6, 9, and 12
14. Weeks 1, 2, 4, 6, 9, and 12
15. Weeks 1, 2, 4, 6, 9, and 12
16. Weeks 1, 2, 4, 6, 9, and 12
17. Weeks 1, 2, 4, 6, 9, and 12
18. Weeks 1, 2, 4, 6, 9, and 12
E.5.2Secondary end point(s)
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 (Panel B)
6. Percentage of participants with need for antifungal concomitant and posttreatment therapy (Panel B)
E.5.2.1Timepoint(s) of evaluation of this end point
1. Day 1 and Day 2
2. Up to 98 days
3. Up to 98 days
4. Up to 84 days
5. Up to Day 28
6. Up to 84 days
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis Yes
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy No
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other Yes
E.8.1.7.1Other trial design description
Sequential-panel
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial1
E.8.3 Will this trial be conducted at a single site globally? No
E.8.4 Will this trial be conducted at multiple sites globally? Yes
E.8.6 Trial involving sites outside the EEA
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3Specify the countries outside of the EEA in which trial sites are planned
Israel
Peru
Russian Federation
Ukraine
United States
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.2In all countries concerned by the trial months30
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 40
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Yes
F.1.1.2.1Number of subjects for this age range: 10
F.1.1.3Newborns (0-27 days) Yes
F.1.1.3.1Number of subjects for this age range: 10
F.1.1.4Infants and toddlers (28 days-23 months) Yes
F.1.1.4.1Number of subjects for this age range: 20
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) No
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations No
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception No
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.2 For a multinational trial
F.4.2.2In the whole clinical trial 40
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
None
G. Investigator Networks to be involved in the Trial
H.4 Third Country in which the Trial was first authorised
H.4.1Third Country in which the trial was first authorised: Russian Federation

Sponsors and Collaborators

Medical Conditions

Drug Interventions

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