Clinical Trials Register

Summary
EudraCT Number:	2019-002408-42
Sponsor's Protocol Code Number:	ASPER-III-19-1
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-01-22
Trial results	View 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
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-002408-42

A.3

Full title of the trial

A Phase 3, Double-Blind, Multicentric, Randomised, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of Itraconazole Dry Powder for Inhalation for the Prevention of Invasive Mould Disease in Patients with Acute Leukaemia and Neutropaenia

Studio di fase 3, in doppio cieco, multicentrico, randomizzato, controllato con placebo per valutare l’efficacia, la sicurezza e la tollerabilità di itraconazolo in polvere asciutta per inalazione per la prevenzione delle micosi invasive in pazienti con leucemia acuta e neutropenia

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study aiming at proving the efficacy, safety and tolerability of inhaled Itraconazole in the prevention of Invasive Mould Disease (infections of the lungs by fungi) in patients with Acute Leukaemia and Neutropaenia (abnormally low concentration of neutrophils in the blood)

Studio con lo scopo di valutare l’efficacia, la sicurezza e la tollerabilità di Itraconazolo inalato nella prevenzione delle micosi invasive (infezioni dei polmoni causate da funghi) in pazienti con leucemia acuta e neutropenia (anormale riduzione della concentrazione di neutrofili nel sangue)

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

ASPER-III-19-1

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	LABORATOIRES SMB S.A
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	LABORATOIRES SMB S.A
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	LABORATOIRES SMB S.A
B.5.2	Functional name of contact point	CLINICAL DEPARTMENT
B.5.3	Address:
B.5.3.1	Street Address	26-28 Rue de la Pastorale
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1080
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003224114828
B.5.5	Fax number	003224112828
B.5.6	E-mail	Dpt_Clinique@smb.be

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/18/2024
D.3 Description of the IMP
D.3.1	Product name	ITRACONAZOLE 4.8 mg
D.3.2	Product code	[ITRACONAZOLE 4.8 mg]
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ITRACONAZOLE
D.3.9.1	CAS number	84625-61-6
D.3.9.2	Current sponsor code	ITRACONAZOLE
D.3.9.4	EV Substance Code	SUB08353MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fungolon 50 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Actavis EAD, Bulgaria
D.2.1.2	Country which granted the Marketing Authorisation	Bulgaria
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fluconazole 50 mg
D.3.2	Product code	[Fluconazole 50 mg]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fluconazole
D.3.9.1	CAS number	86386-73-4
D.3.9.2	Current sponsor code	Fluconazole
D.3.9.4	EV Substance Code	SUB07674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fungolon 100 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Actavis EAD, Bulgaria
D.2.1.2	Country which granted the Marketing Authorisation	Bulgaria
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fluconazole 100 mg
D.3.2	Product code	[Fluconazole]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fluconazole
D.3.9.1	CAS number	86386-73-4
D.3.9.2	Current sponsor code	fluconazole
D.3.9.4	EV Substance Code	SUB07674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Diflazon 2 mg/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	KRKA, d.d.
D.2.1.2	Country which granted the Marketing Authorisation	Slovenia
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fluconazole 2 mg/ml
D.3.2	Product code	[Fluconazole 2 mg/ml]
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fluconazole
D.3.9.1	CAS number	86386-73-4
D.3.9.2	Current sponsor code	Fluconazole
D.3.9.4	EV Substance Code	SUB07674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder, hard capsule
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

prevention of invasive mould disease

prevenzione delle micosi invasive

E.1.1.1

Medical condition in easily understood language

Infection of the lungs by fungi

Infezione dei polmoni da funghi

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10003488
E.1.2	Term	Aspergillosis
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate whether prophylaxis with ITZ DPI can reduce the incidence rate of IMD in patients with acute leukaemia undergoing remission induction chemotherapy

Indagare se la profilassi con ITZ DPI possa ridurre il tasso di incidenza delle micosi invasive (IMD) in pazienti con leucemia acuta sottoposti a chemioterapia di induzione della remisione

E.2.2

Secondary objectives of the trial

-To investigate the safety and tolerability of ITZ DPI in patients with acute leukaemia undergoing remission-induction chemotherapy
-To evaluate the PK of ITZ DPI in patients with acute leukaemia undergoing remission induction chemotherapy

- Indagare la sicurezza e la tollerabilità di ITZ DPI in pazienti con leucemia acuta sottoposti a chemioterapia di induzione della remissione
- Valutare la farmacocinetica (PK) di ITZ DPI in pazienti con leucemia acuta sottoposti a chemioterapia di induzione della remissione

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male or female patients =12 years of age
2.Patients with new or relapsed ALL or AML who cannot receive posaconazole for any reason and who are to undergo remission-induction chemotherapy
3.Current neutropaenia resulting from the diagnosis of new or relapsed acute leukaemia or patients with expected neutropaenia for at least 10 days (an absolute neutrophil count <500 cell/mm3 or 0.5 x 109 cell/L) following remission-induction chemotherapy
4.Able to have all Screening tests performed quickly to ensure results can be obtained and evaluated before randomisation, so that the first dose of study drug for the prevention of IMD can be administered as soon as possible within 5 days of the start of remission induction chemotherapy. In ALL patients, as soon as possible within 5 days of the start of remission-induction chemotherapy means as soon as possible within 5 days of the start of high dose steroid therapy.
5.Able to comply with all study procedures, including the use of inhalers
6.If patient is a female of childbearing potential (FOCP), patient must agree to use an effective means of birth control (oral contraceptives, intrauterine device [IUD], condoms and spermicides, vaginal ring, hormonal patch, implants), as determined by the Investigator from the first dose of study drug until 100 days following the last dose of study drug. Female patients of childbearing potential must also provide a negative blood pregnancy test at the Screening Visit. Male patients must be vasectomised, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and also agree not to donate sperm from the first dose of study drug until 100 days following the last dose of study drug.

1. Pazienti maschi o femmine di età =12 anni
2. Pazienti con LAL o LAM di nuova insorgenza o recidivante che non possono ricevere posaconazolo per qualsiasi motivo e che sono in procinto di sottoporsi a chemioterapia di induzione della remissione
3. Attuale neutropenia conseguente alla diagnosi di leucemia acuta di nuova insorgenza o recidivante oppure neutropenia prevista per almeno 10 giorni (conta assoluta dei neutrofili <500 cellule/mm3 o 0,5 x 109 cellule/l) dopo la chemioterapia di induzione della remissione
4. Possibilità di effettuare tutti gli esami di screening rapidamente per garantire che i risultati possano essere ottenuti e valutati prima della randomizzazione, così da permettere di somministrare la prima dose di farmaco dello studio per la prevenzione delle IMD il prima possibile entro 5 giorni dall’avvio della chemioterapia di induzione della remissione. Nei pazienti con LAL, il prima possibile entro 5 giorni dall’avvio della chemioterapia di induzione della remissione significa il prima possibile entro 5 giorni dall’inizio della terapia con steroidi ad alte dosi
5. Capacità di attenersi a tutte le procedure dello studio, compreso l’uso di inalatori
6. Qualora la paziente sia una donna in età fertile (FOCP), consenso all’uso di metodi contraccettivi efficaci (contraccettivi orali, dispositivo intrauterino [IUD], preservativi e spermicidi, anello vaginale, cerotto ormonale, impianti), come stabilito dallo sperimentatore, dalla prima dose di farmaco dello studio fino a 100 giorni dopo l’ultima dose di farmaco dello studio. Le pazienti in età fertile devono inoltre disporre di un test di gravidanza sul sangue negativo alla visita di screening. I pazienti di sesso maschile devono essere vasectomizzati, astenersi dai rapporti sessuali o acconsentire all’uso di una contraccezione barriera (preservativo con spermicida), nonché a non donare sperma dalla prima dose di farmaco dello studio fino a 100 giorni dopo l’ultima dose di farmaco dello studio

E.4

Principal exclusion criteria

1.Proven, probable, or possible IMD (according to the most recent European Organisation for Research and Treatment of Cancer/National Institute of Allergy and Infectious Diseases Mycoses Study Group [EORTC/MSG] criteria) at Screening or in the patient's medical history
2.Pulmonary complications or infiltrates assessed by a chest CT
3.Patients with ventricular dysfunction defined as ejection fraction <55% at Screening
4.Concomitant or previous treatment with a mould-active antifungal drug within 30 days, unless the plasma level is below the limit of detection or =5 half-lives of the antifungal has elapsed since the treatment was given.
5.Participating in another clinical trial with exposure to any investigational drug within 30 days prior to Screening, with the exception of the current anti-leukemic treatment
6.Pregnant or nursing females
7.Any severe co-morbidity other than underlying haematological disease that may interfere with study procedures or affect the patient's safety
8.Grade 3 liver function test results, including aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), or total bilirubin >5 times the upper limit of normal (ULN)
9.Any contraindication or hypersensitivity to the use of fluconazole or ITZ or the excipient (mannitol) in the study drug and placebo formulations
10.Co-administration of astemizole, atorvastatin, bepridil, cisapride, dihydroergotamine, dofetilide, eletriptan, ergometrine (erginovine), ergotamine, erythromycin, levacetylmethadol (levomethadyl), lovastatin, methylergometrine (methylergonovine), midazolam, mizolastine, nisoldipine, pimozide, quinidine, sertindole, simvastatin, terfenadine and triazolam.
11.Abnormal QT interval corrected by Fridericia (QTcF): males >450 ms and females >470 ms

1. IMD dimostrata, probabile o possibile (secondo i criteri più recenti dell’Organizzazione europea per la ricerca e il trattamento del cancro/Istituto nazionale di allergologia e infettivologia - Gruppo di studio sulle micosi [EORTC/MSG]) allo screening o nell’anamnesi medica del paziente
2. Complicanze o infiltrati polmonari valutati mediante TC del torace
3. Disfunzione ventricolare, definita come frazione di eiezione <55% allo screening
4. Trattamento concomitante o precedente, entro 30 giorni, con un farmaco antimicotico attivo contro le muffe, a meno che il livello plasmatico non sia al di sotto del limite di rilevabilità o non siano trascorse =5 emivite dell’antimicotico dalla somministrazione del trattamento
5. Partecipazione a un’altra sperimentazione clinica con esposizione a qualsiasi farmaco sperimentale entro 30 giorni prima dello screening, con l’eccezione dell’attuale trattamento antileucemico
6. Gravidanza o allattamento
7. Qualsiasi comorbilità grave al di fuori della malattia ematologica di base che possa interferire con le procedure dello studio o compromettere la sicurezza del paziente
8. Risultati dei test di funzionalità epatica di grado 3, tra cui livelli di aspartato aminotransferasi (AST), alanina aminotransferasi (ALT) o bilirubina totale >5 volte il limite superiore della norma (ULN)
9. Qualsiasi controindicazione o ipersensibilità all’uso di fluconazolo o ITZ, oppure all’uso dell’eccipiente (mannitolo) contenuto nelle formulazioni di farmaco dello studio e di placebo
10. Co-somministrazione di astemizolo, atorvastatina, bepridil, cisapride, diidroergotamina, dofetilide, eletriptan, ergometrina (ergonovina), ergotamina, eritromicina, levacetilmetadolo (levometadil), lovastatina, metilergometrina, (metilergonovina), midazolam, mizolastina, nisoldipina, pimozide, chinidina, sertindolo, simvastatina, terfenadina e triazolam
11. Anomalie dell’intervallo QT corretto mediante Fridericia (QTcF) (>450 ms negli uomini, >470 ms nelle donne)

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the:
Proportion of patients with proven or probable IMD at EOT. Diagnoses of proven or probable IMD will be evaluated according to the most recent EORTC/MSG criteria, as assessed by the Independent Data Review Board
(IDRB) that will be blinded to treatment assignment.

Percentuale di pazienti con IMD dimostrata o probabile all’EOT. Le diagnosi di IMD dimostrata o probabile saranno valutate secondo i criteri EORTC/MSG più recenti dal Comitato indipendente di revisione dei dati (IDRB), che sarà in cieco rispetto all’assegnazione del trattamento

E.5.1.1

Timepoint(s) of evaluation of this end point

End of treatment

fine del tratamento

E.5.2

Secondary end point(s)

The secondary efficacy endpoints are:
•Treatment success at EOT (success defined as patients who completed treatment without developing a proven, probable, or possible IMD, without requiring systemic mould-active antifungal treatment, without
discontinuation from the study due to an adverse event [AE], and who are alive).
•The proportion of patients:
o with proven, probable, or possible IMD at EOT and EOS
o who had neutropaenia =10 days and with proven, probable, or possible IMD at EOT and EOS
o with radiographic pulmonary infiltrates according to the central image reader at EOT and EOS
o with bronchopulmonary aspergillosis at EOT and EOS
o with fungal sinusitis at EOT and EOS
o with proven or probable or possible IA at EOT and at EOS
o with candidemia/candidiasis at EOT and EOS
o requiring systemic mould-active antifungal treatment at EOT and EOS to treat a breakthrough fungal infection
o alive at EOT and EOS
o who died at EOT and EOS due to IMD or IA
o in complete remission of their underlying malignancy at EOT and EOS
•The proportion of pathogenic moulds causing proven and probable IMDs at EOT and EOS
•Time to:
o diagnosis of proven, probable, or possible IMD
o diagnosis of IA
o the onset of systemic mould-active antifungal treatment for a breakthrough fungal infection
o death of any cause

• Successo del trattamento all’EOT (successo definito come pazienti che hanno completato il trattamento senza sviluppare una IMD dimostrata, probabile o possibile, senza richiedere un trattamento antimicotico attivo contro le muffe di tipo sistemico e senza dover interrompere lo studio a causa di un evento avverso [EA] e che sono in vita)
• Percentuale di pazienti:
o con IMD dimostrata, probabile o possibile all’EOT e all’EOS
o che hanno manifestato neutropenia di durata =10 giorni e con IMD dimostrata, probabile o possibile all’EOT e all’EOS
o con infiltrati polmonari visibili radiograficamente secondo il lettore centrale delle immagini all’EOT e all’EOS
o con aspergillosi broncopolmonare all’EOT e all’EOS
o con sinusite fungina all’EOT e all’EOS
o con aspergillosi invasiva (AI) dimostrata o probabile o possibile all’EOT e all’EOS
o con candidemia/candidosi all’EOT e all’EOS
o con necessità di trattamento antimicotico attivo contro le muffe di tipo sistemico all’EOT e all’EOS per la gestione di un’infezione fungina intercorrente
o vivi all’EOT e all’EOS
o deceduti all’EOT e all’EOS in seguito a IMD o IA
o in remissione completa dalla neoplasia di base all’EOT e all’EOS
• Percentuale di muffe patogene responsabili di IMD dimostrate e probabili all’EOT e all’EOS
• Tempo:
o alla diagnosi di IMD dimostrata, probabile o possibile
o alla diagnosi di IA
o all’avvio di un trattamento antimicotico attivo contro le muffe di tipo sistemico per un’infezione fungina intercorrente
o al decesso per qualsiasi causa

E.5.2.1

Timepoint(s) of evaluation of this end point

End of treatment and end of study

Fine del tratamento e fine dello studio

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Russian Federation

Serbia

Ukraine

Belgium

Bulgaria

Greece

Italy

Poland

Romania

Spain

E.8.7

Trial 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.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

339

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

281

F.4.2.2

In the whole clinical trial

462

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

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-04-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-20

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-05-27

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