Clinical Trials Register

Summary
EudraCT Number:	2011-000499-32
Sponsor's Protocol Code Number:	FSJD-ABELNEB-2010
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2011-06-30
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
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

Spain - AEMPS

A.2

EudraCT number

2011-000499-32

A.3

Full title of the trial

A PHASE II CLINICAL TRIAL TO EVALUATE THE SAFETY AND TOLERABILITY OF AMPHOTERICIN B LIPID COMPLEX (ABELCET®) FOR THE PROPHYLAXIS OF INVASIVE PULMONARY ASPERGILLOSIS DURING PROLONGED NEUTROPENIA IN PAEDIATRIC PATIENTS WITH ACUTE LEUKAEMIA

ENSAYO CLÍNICO DE FASE II PARA EVALUAR LA SEGURIDAD Y LA TOLERABILIDAD DE AMFOTERICINA B COMPLEJO LIPÍDICO (ABELCET®) NEBULIZADO PARA LA PROFILAXIS DE LA ASPERGILOSIS PULMONAR INVASIVA DURANTE LA NEUTROPENIA PROLONGADA EN LOS PACIENTES PEDIÁTRICOS CON LEUCEMIA AGUDA

A.3.1

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

A.4.1

Sponsor's protocol code number

FSJD-ABELNEB-2010

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	FUNDACIÓ SANT JOAN DE DEU
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Ministerio de Sanidad y Política Social.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FUNDACIÓ SANT JOAN DE DEU
B.5.2	Functional name of contact point	FUNDACIÓ SANT JOAN DE DEU
B.5.3	Address:
B.5.3.1	Street Address	C/ Santa Rosa 39-57
B.5.3.2	Town/ city	Esplugues de Llobregat-Barcelona
B.5.3.3	Post code	08950
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3493600 97 51
B.5.5	Fax number	+3493600 97 71
B.5.6	E-mail	rmorales@fsjd.org

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	Yes
D.2.1.1.1	Trade name	ABELCET 5 mg/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Cephalon Pharma, S.L.U.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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.3.4	Pharmaceutical form	Suspension for infusion
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.3.9.1	CAS number	1397-89-3
D.3.9.3	Other descriptive name	AMPHOTERICIN B
D.3.9.4	EV Substance Code	SUB05486MIG
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	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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Invasive pulmonary aspergillosis in patients with acute myeloblastic or lymphoblastic leukaemia.

Aspergilosis pulmonar invasiva en pacientes con leucemia aguda, mieloblástica o linfoblástica.

E.1.1.1

Medical condition in easily understood language

Invasive pulmonary infection due to aspergillus fungus in patients with acute myeloblastic or lymphoblastic leukaemia.

Infección pulmonar invasiva por hongo Aspergillus en pacientes con leucemia aguda, mieloblástica o linfoblástica.

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10022881
E.1.2	Term	Invasive bronchopulmonary aspergillosis
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the overall tolerability of the drug, defined as any adverse event that results in the interruption of treatment, during primary prophylaxis with nebulized ABLC, in paediatric patients with acute leukaemia (AL) undergoing intensive chemotherapy.

Evaluar la tolerabilidad global del fármaco, definida como cualquier acontecimiento adverso que suponga la interrupción del tratamiento, durante la profilaxis primaria con ABCL nebulizado, en pacientes pediátricos con leucemia aguda (LA) tratados con quimioterapia intensiva.

E.2.2

Secondary objectives of the trial

1.To evalute the efficacy of primary prophylaxis with nebulized ABLC on the incidence of invasive pulmonary aspergillosis (IPA) in paediatric patients with LA undergoing intensive chemotherapy.
2.To determine the IPA-related mortality during primary prophylaxis with ABLC in paediatric patients with (AL) undergoing intensive chemotherapy.

1.Evaluar la eficacia de la profilaxis primaria con ABCL nebulizado sobre la incidencia de aspergilosis pulmonar invasiva (API) en pacientes pediátricos con LA tratados con quimioterapia intensiva.
2.Evaluar la mortalidad relacionada a la API durante la profilaxis primaria con ABCL nebulizado en pacientes pediátricos con LA tratados con quimioterapia intensiva.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age: patients between 3 and 18 years.
2. Diagnosis of myeloblastic or lymphoblstic AL during intensive chemotherapy.
3. Informed consent of parents/guardians and/or assent of the patient has been obtained.

1.Edad: pacientes menores de entre 3 y 18 años.
2.Diagnóstico de LA mieloblástica o linfoblástica en fase de tratamiento con quimioterapia intensiva.
3.Obtención del consentimiento informado de padres/tutores y/o asentimiento del paciente.

E.4

Principal exclusion criteria

1.Probable or proven invasive pulmonary fungal infection before entering the trial.
2.Previous chronic renal impairment or baseline serum creatinine > 2.5 mg /dL
3.Severe hepatic impairment.
4.Moderate-severe asthma being treated pharmacologically.
5.Antifungal treatment for filamentous fungi in the last 4 weeks.
6.Participating or have participated in a clinical trial during the last 4 weeks.
7.Mentally retarded
8.Known allergy or hypersensitivity to the active ingredient of the study drug or to any of its excipients.
9.Any serious concomitant disease that in the investigator?s opinion could compromise the completion of the trial or affect the patient?s tolerability to this treatment.
10.Pregnancy (in women of fertile age).
11.Breast-feeding.

Patients are defined as having probable IFI when their radiological image is suggestive of fungal infection and they have positive antigenemia for Aspergillus. IFI would be proven when the presence of Aspergillus is confirmed in aspirate culture or by lung biopsy.

1.Infección fúngica invasiva pulmonar (IFI) probable o probada antes de entrar en el ensayo.
2.Insuficiencia renal crónica previa o creatinina sérica basal > 2,5 mg /dl
3.Insuficiencia hepática grave.
4.Asma moderado-grave en tratamiento farmacológico.
5.Tratamiento con antifúngicos contra hongos filamentosos en las últimas 4 semanas.
6.Participar o haber participado en un ensayo clínico durante las últimas 4 semanas.
7.Retraso mental.
8.Alergia o hipersensibilidad conocida al principio activo del fármaco en investigación, o a cualquiera de sus excipientes.
9.Cualquier enfermedad concomitante grave que en la opinión del investigador pueda comprometer completar el estudio o afectar la tolerancia del paciente para este tratamiento.
10.Embarazo (en las mujeres en edad fértil).
11.Lactancia.

Se define como IFI probable aquella en los que el paciente presenta una imagen radiológica sugestiva de infección fúngica y antigenemia positiva por Aspergillus. La IFI quedaría probada cuando se confirmara la presencia de Aspegillus en cultivo de aspirado o por biopsia pulmonar

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable will be the proportion of patients who discontinue prophylactic treatment with ABLC due to an adverse event that is related or not to the study drug or for intolerability to it.

La variable primaria de eficacia será la proporción de pacientes que discontinúan el tratamiento profiláctico con ABCL por un acontecimiento adverso relacionado o no con el fármaco en estudio o por intolerancia al mismo.

E.5.1.1

Timepoint(s) of evaluation of this end point

They will be analysed by homogeneity tests comparing the results with those of a historical cohort. The hypothesis tests and confidence intervals will be calculated by exact methods given the low sample size.

Se analizarán mediante pruebas de homogeneidad comparando los resultados observados respecto a la cohorte histórica. Las pruebas de hipótesis e intervalos de confianza se calcularán por métodos exactos dado el bajo tamaño de la muestra.

E.5.2

Secondary end point(s)

The secondary variables to be obtained are the following:

-Proportion of discontinued drug administrations due to a treatment-related adverse event or intolerability to treatment (number of discontinued administrations/ number of administrations started)
-Total number of IPA cases
-Incidence of IPA during the ABLC (Abelcet®) prophylactic treatment period (number of patients with IPA/number of patients on prophylaxis).
-IPA incidence rate during the ABLC prophylactic treatment period (number of patients with aspergillosis/time on prophylaxis of study patients).
-Mortality due to IPA
-Percentage of deaths during the prophylactic treatment period and cause of death.

Se recogerán las siguientes variables secundarias:
-Proporción de administraciones del fármaco que discontinúan por un acontecimiento adverso relacionado con el tratamiento o intolerancia al mismo (nº administraciones interrumpidas/nº administraciones iniciadas )
-Número total de casos de API
-Incidencia de API durante el período de tratamiento profiláctico con ABLC (Abelcet®) (nº de pacientes con API/nº de pacientes en profilaxis).
-Tasa de incidencia de API durante el período de tratamiento profiláctico con ABCL (nº pacientes con aspergilosis/tiempo en profilaxis de los pacientes en estudio)
-Mortalidad por API
-Porcentaje de fallecidos durante el tratamiento profiláctico y causa de fallecimiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

For the analysis of patients who died due to IPA or other causes a Kaplan-Meier survival analysis will be performed. The median survival time and the % of cumulative survival will be estimated with their respective 95% confidence intervals.
The 95% confidence interval (95% CI) will be calculated for the presence/absence of toxicity and toxicity severity (CTCAE grades 1 to 4) variable. All the adverse events will be listed giving their severity and relation to the study drug. The categorical variables will be will be summarised by frequency distributions whilst the central tendency and dispersion will be given for the quantitative variables and, if appropriate, their 95% confidence intervals (95% CI).

Para el análisis de pacientes fallecidos por API u otras causas se realizará un análisis de supervivencia mediante el método de Kaplan-Meier. Se estimarán la mediana del tiempo de supervivencia y el % de supervivencia acumulada, con sus intervalos de confianza respectivos al 95%.
En la variable presencia/ausencia de toxicidad y gravedad de toxicidad (grados CTCAE 1 a 4) se calculará su intervalo de confianza (IC95%). Se listarán todos los acontecimientos adversos considerando su gravedad y su relación con el fármaco en estudio. Las variables categóricas se resumirán mediante distribuciones de frecuencias mientras que, para las variables cuantitativas, se informará de tendencia central y dispersión y, si es apropiado, se presentará su intervalo de confianza al 95% (IC95%).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

No aplica

Not applicable

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

Last patient last visit will be the end of the trial

El final del ensayo coincide con la última visita del último sujeto
reclutado en el ensayo

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

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

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)

F.1.3

Elderly (>=65 years)

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2011-06-30.

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Infants less than 11 years old.

Niños menores de 11 años de edad.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

Not applicable

No aplica

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

2011-09-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-29

P. End of Trial
P.	End of Trial Status	Ongoing

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