Clinical Trials Register

Summary
EudraCT Number:	2013-003714-40
Sponsor's Protocol Code Number:	HCQinpediatricILD
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-11-05
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

2013-003714-40

A.3

Full title of the trial

Hydroxychloroquine in pediatric ILD START randomized controlled in parallel-group, then switch placebo to active drug, and STOP randomized controlled in parallel-group
to evaluate the efficacy and safety of hydroxychloroquine (HCQ)

Hidroxicloroquina en EPI pediátrica. START aleatorizado, controlado, de grupos paralelos, con cambio de placebo a fármaco activo, y STOP aleatorizado, controlado, de grupos paralelos, para evaluar la eficacia y seguridad de hidroxicloroquina (HCQ)

A.3.1

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

HCQ in pediatric ILD

HCQ en EPI pediátrica

A.3.2

Name or abbreviated title of the trial where available

HCQ in pediatric ILD

HCQ en EPI pediátrica

A.4.1

Sponsor's protocol code number

HCQinpediatricILD

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02615938

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	Klinikum der Universität München
B.1.3.4	Country	Germany
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	EUROPEAN COMMISSION DIRECTORATE-GENERAL FOR RESEARCH & INNOVATION
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fundación Hospital Universitari Vall d'Hebron - Institut de recerca
B.5.2	Functional name of contact point	ARO -ACADEMIC RESEARCH ORGANIZATION
B.5.3	Address:
B.5.3.1	Street Address	Passeig de la Vall d'Hebron, 119-129
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08035
B.5.3.4	Country	Spain
B.5.4	Telephone number	349348930002702
B.5.6	E-mail	aro@vhir.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	No
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	hydrochloroquine
D.3.4	Pharmaceutical form	Capsule
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	HYDROXYCHLOROQUINE
D.3.9.1	CAS number	118-42-3
D.3.9.4	EV Substance Code	SUB08077MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6.5
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.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	No
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	hydrochloroquine
D.3.4	Pharmaceutical form	Capsule
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	HYDROXYCHLOROQUINE
D.3.9.1	CAS number	118-42-3
D.3.9.4	EV Substance Code	SUB08077MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

interstitial lung disease

enfermedad pulmonar intersticial de la infancia (chILD, children´s interstitial lung disease)

E.1.1.1

Medical condition in easily understood language

interstititial lung disease

enfermedad pulmonar intersticial de la infancia (chILD, children´s interstitial lung disease)

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	PT
E.1.2	Classification code	10022611
E.1.2	Term	Interstitial lung disease
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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

START HCQ block
To evaluate the efficacy of HCQ after 28 days of treatment in chILD compared to placebo.

STOP HCQ block
To evaluate the efficacy of HCQ after 84 days of treatment in chILD compared to Placebo

Bloque START:
Evaluar la eficacia de HCQ en chILD a los 28 días de tratamiento en comparación con placebo.

Bloque STOP:
Evaluar la eficacia de HCQ en chILD a los 84 días de tratamiento en comparación con placebo.

E.2.2

Secondary objectives of the trial

START HCQ block
- To evaluate the efficacy of HCQ after 56 days of treatment in chILD compared to 28 days.
- To evaluate the safety of HCQ after 28 and 56 days of treatment in chILD.
- To evaluate blood levels of HCQ after 28 and 56 days of treatment in chILD.

STOP HCQ block
- To evaluate the efficacy of chronic (> 3 months) HCQ treatment in chILD compared to placebo.
- To evaluate the safety of HCQ after > 3 months of treatment in chILD.
- To evaluate blood levels of HCQ before and after treatment in chILD

- Evaluar la eficacia de HCQ en chILD a los 56 días de tratamiento y compararla con los resultados a los 28 días de tratamiento.

- Evaluar la seguridad de HCQ en chILD a los 28 y 56 días de tratamiento.

- Evaluar los niveles sanguíneos de HCQ en chILD a los 28 y 56 días de tratamiento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Patients should be clinically stable during baseline (between Visit 1 and 2) for inclusion into the study
a) To determine this, attending physicians can use SpO2 in room air for patients on room air or on O2-supplement; the absolute difference on SpO2 is expected not to be ≥ 5% between Visit 1 and 2. For patients on respiratory support, the summary key parameters should not change ≥ 20% between Visit 1 and 2
and
b) No major changes in other medications between Visit 1 and 2
2)Mature newborn ≥ 37 weeks of gestation, age ≥ 3 wks and < 2y
or
Infants and children (≥ 2 y and < 18 y)
or
Adults (≥18 and ≤30 y)
or
Previously preterm (≤ 37 weeks of gestation) babies or children and adults of all ages if chILD genetically diagnosed (see inclusion criterion 3.)
3) Diagnosis of chronic (≥ 3 wks of duration) diffuse parenchymal lung disease (DPLD = chILD), defined in at least one of the following ways:
a) chILD genetically diagnosed
Surfactant dysfunction disorders including patients with mutations in SFTPC, SFTPB, ABCA3, TTF1 (Nkx2-1), further extremely rare entities with specific mutations, for example in TBX4, NPC2, NPC1, NPB, COPA, LRBA and other genes. In this case, also previously preterm (≤ 37 weeks of gestation) babies or children and adults of all ages can be included into the study.
b) chILD histologically diagnosed
• Chronic pneumonitis of infancy (CPI)
• Desquamative interstitial pneumonia (DIP)
• Lipoid pneumonitis / Cholesterol pneumonia
• Nonspecific interstitial pneumonia (NSIP)
• PAP after the exclusion of mutations in GMCSF-Ra/b and GMCSF autoantibodies*
• Usual interstitial pneumonia (UIP)
• Follicular bronchitis/ bronchiolitis/ Lymphogenic interstitial pneumonia (LIP)
• Storage disease with primary pulmonary involvement (e.g. Nieman Pick)
• Hermansky Pudlak Syndrome
• Idiopathic pulmonary haemorrhage (haemosiderosis)*
• Other histology diagnosing chILD, in particular combination of the above pattern, but not exclusively
4) Start block: no HCQ treatment in the last 12 weeks
Stop block: stable HCQ treatment for at least the last 12 weeks
5) Ability of subject or/and legal representatives to understand character and individual consequences of clinical trial.
6) Signed and dated informed consent of the subject (if the subject has the ability) and the representatives (of underaged children) must be available before start of any specific trial procedures.

1) Los pacientes deberían encontrarse clinicamente estables durante el periodo inicial (entre la visita 1 -2) para la inclusión en el estudio.
a) Para su determinación, los médicos pueden usar SpO2 en pacientes que se encuentren en habitaciones al aire libre o aquellos que necessiten suplementación de oxigeno. La diferencia absoluta para SpO2 no se prevee que sea ≥ 5% entre la visita 1 y 2. Para pacientes con asistencia respiratòria, los parametros claves resuminos no deben cambiar ≥ 20% entre la visita 1 y 2.
Además,
b) Que no existan cambios importante en otras medicaciones entre la visita 1 y 2.

2) Recién nacidos maduros (≥ 37 semanas de gestación, edad ≥ 3 semanas y < de 2 años) o bebes y ninos (≥ 2 años y < 18 años) o adultos (≥18 y ≤30 años).
También, para el caso de bebes pre-términos (≤ 37 semanas de gestación) o ninos y adultos de todas las edades, si han sido diagnosticados geneticamente para chILD (ver criterio de inclusión 3)

3) Diagnostico de Enfermedad pulmonar parenquimatosa difusa (DPLD= chILD) crònica (≥ 3 semanas de duración), descrito en, al menos, una de las siguientes formas:
a) Diagnosticado geneticamente para chILD, definiéndose ello como: mutaciones en SFTPC, SFTPB, ABCA3, TTF1 (Nkx2-1), mutacions específicas en pacientes con enfermedades extremadamente rares (por ejemplo: mutaciones en TBX4, NPC2, NPC1, NPB, COPA, LRBA y otros genes). En este caso, estos pacientes podran ser incuidos dentro del estudio.
b) Historial diagnostico para chILD, a partir de las siguientes afecciones:
• Neumonia crònica infantil (CPI)
• Neumonía insterticial descamativa (DIP)
• Neumonitis lipoidea / Neumonia por colesterol
• Neumonia intersticial no especifica (NSIP)
• PAP después de la exclusión de mutaciones en GMCSF-Ra/b y GMCSF auto-anticuerpos*
• Neumonía intersticial común (UIP)
• Follicular bronchitis/ bronchiolitis/ Lymphogenic interstitial pneumonia (LIP)
• Enfermedad de almacenamiento con pariticipación primaria pulmonar (e.g. Nieman Pick)
• Síndrome Hermansky Pudlak
• Hemorragia pulmonar idiopática (haemosiderosis)*
• otro tipo de historial diagnostico para chILD, a través de la combinación de las afecciones arriba comentada, però no solo exclusivamente por estas.
4) Bloque START: los pacientes no pueden haber sido tratados con HCQ en las últimes 12 semanas.
El bloque STOP: Los pacientes deben de haber tenido un tratamiento estable de HCQ por, al menos, las 12 últimas semanas.
5) Capacidad del sujeto y/o representante legal para entender la naturaleza y las consecuencias del ensayo clínico.
6) Firma y fecha del consentimiento informado por el paciente (si el paciente puede realizar ello) y el representante (en caso de menores de edad) debe ser estar disponible antes de començar cualquier actividad expecífica del procedimiento del ensayo.

E.4

Principal exclusion criteria

Subjects presenting with any of the following criteria will not be included in the trial:
- chILD primarily related to developmental disorders
- chILD primarily related to growth abnormalities reflecting deficient alveolarisation
- hILD related to chronic aspiration
- chILD related to immunodeficiency
- chILD related to abnormalities in lung vessel structure
- chILD related to organ transplantation/organ rejection/GvHD
- chILD related to recurrent infections
- Acute severe infectious exacerbations
- Known hypersensitivity to HCQ, or other ingredients of the tablets (lactose-monohydrate, povidone, maize starch, magnesium stearate, hypromellose, macrogol or titanium dioxide (E 171), silicon dioxide or mannitol), to sucrose-octaacetate or sodium saccharine.
- Proven retinopathy or maculopathy
- Glucose-6-phosphate-dehydrogenase deficiency resulting in favism or hemolytic anemia
- Myasthenia gravis
- Hematopoetic disorders
- Pregnancy and lactation (Women with childbearing potential have to practice a medically accepted contraception during trial and till three months after the end of the treatment with HCQ, and a negative pregnancy test (serum or urine) should be existent on Visit 1, if girls of childbearing age and only if sexual relations are known or probable. It is at the discretion and responsibility of the attending physician to decide, whether a pregnancy test is necessary or not. Reliable contraception are systematic contraceptives (oral, implant, injection). Women that are sterile by surgery can participate in the trial. At the discretion of the investigator, sexual abstinence is also accepted as contraceptive method. Girls after menarche have to receive a counselling about birth control methods in presence of at least one parent, which has to be documented in the patient notes.
- Participation in other clinical trials during the present clinical trial or not beyond the time of 4 half-lives of the medication used, at least one week.
- Hereditary galactose intolerance, lactase deficiency or glucose-galactose-malabsorption
- Renal insufficiency at screening, defined as glomerular filtration rate (GFR)
o < 40 mL/min/1.73 m2 in patients age 3 to 8 weeks
o < 60 mL/min/1.73 m2 in patients ≥ 8 weeks of Age (KDIGO guideline 2012, K/DOQI guideline 2002)
- Liver disease, gastrointestinal disorder, haematological disorder, epilepsy or other neurological disorder, psoriasis, porphyria at the discretion of the treating physician
- Simultaneous prescription of other potentially nephrotoxic or hepatotoxic medication at the discretion of the treating physician

Los sujetos que presenten alguno de los sigueintes criterios no seran incluidos en el ensayo:
1) chILD relacionado primordialmente con trastornos del desarrollo.
2) chILD relacionado primordialmente con anormalidades en el crecimiento reflejado en una deficiència de la alveolarización.
3) chILD relacionado primordialmente con aspiración crònica
4) chILD relacionado primordialmente con inmunodeficiencia
5) chILD relacionado primordialmente con anormalidades en la estructura de los vasos pulmonares
6) chILD relacionado primordialmente con trasplante de órganos/ rechazo de órganos/ GvHD
7) chILD relacionado primordialmente con infección concurrente
8) Exacerbación de una infección aguda grave.
9) Conocimiento de hipersensibilidad a HCQ u otro excipiente de la cápsula a utilizar en el ensayo como HCQ (lactosa-monohidrato, povidona, almidón de maíz, estearato magnésico, hipromelosa, macrogol o dióxido de titanio (E-171), dióxido de silicona o manitol), o también a octoacetato de sacarosa o sacarina sódica.
10) Retinopatía o maculopatía probada.
11) Deficiencia de glucosa-6-fosfato-dihidrogenasa (favism) o anemia hemolítica
12) Miastenia grave
13) Desordenes hematopoyético
14) Embarazo y lactancia (mujeres en edad fértil o potencialmente fértil tienen que aceptar un método anticonceptivo durante el ensayo y hasta 3 meses después de la finalización del tratamiento con HCQ. Además, un resultado negativo en la prueba de embarazo (por serum u orina) debe de existir en la visita 1, en aquellas chicas en edad fértil y que se conozca o sea probable las relaciones sexuales. El uso del test de embarazo queda bajo consideración del médico, si debe usarse o no. Los anticonceptivos más viables son: anticonceptivos sistemáticos (orales, implantados, inyectados). En el caso de mujeres estériles quirúrgicamente pueden participar en el ensayo. El método anticonceptivo de la no práctica sexual de los participante queda bajo consideración del médico si quiere usarse o no. Las niñas después de adquirir la menstruación tienen que recibir asesoramiento sobre métodos de control del embarazo, en presencia de al menos, uno de los padres, quedando ello recogido en la historia clínica del paciente.
15) Participación en otros ensayos clínicos durante el tiempo de este ensayo, o que no haya pasado un tiempo más allá de 4 vidas medias del medicamento que se utilizó en el anterior ensayo (al menos 1 semana).
16) Intolerancia hereditaria a la galactosa, deficiencia de lactosa o mala absorción de glucosa-galactosa.
17) Insuficiencia renal en el screening, definido ello a partir de una tasa de infiltración glomerular (GFR) de: o < 40 mL/min/1.73 m2 en pacientes con una edad de entre 3-8 semanas o < 60 mL/min/1.73 m2 en pacientes ≥ 8 semanas de edad (guía KDIGO 2012, guia K/DOQI 2002)
18) Desorden gastrointestinal, enfemerdad hepàtica, desorden hematologico, epilèpsia u otra ptología neurològica, psoriasis, porfíria considerada por el medico que esté tratando.
19) Prescripción simultanea de otros medicamentos neurotóxicos o hepatotóxicos, a criterio del medico.

E.5 End points

E.5.1

Primary end point(s)

START HCQ block
Relative change trial day 1 (i.e. Visit 2) through day 28 (i.e. Visit 3) and relative change day 28 to day 56, (i.e. Visit 4): change active compound compared to change placebo

STOP HCQ block
Relative change trial day 1 (i.e. Visit 2) through day 84 (i.e. Visit 5): change active compound compared to change placebo

Bloque START HCQ
Cambio relativo desde el día 1 del estudio (Visita 2) hasta el día 28 (Visita 3) y cambio relativo del día 28 al día 56 (Visita 4): cambio observado con tratamiento activo en comparación con el cambio observado con placebo.
Bloque STOP HCQ
Cambio relativo en la oxigenación desde el día 1 (Visita 2) hasta el día 84 (Visita 5): cambio observado con tratamiento activo en comparación con el cambio observado con placebo.

E.5.1.1

Timepoint(s) of evaluation of this end point

28/56 / 84 days

28/56 / 84 días

E.5.2

Secondary end point(s)

- For both, START and STOP HCQ blocks absolute and relative change under the active compound from trial day 1 (i.e. Visit 2), to START block: day 28 (i.e. Visit 3), STOP block: day 84 (i.e. Visit 5) each, will be compared to change under placebo. The following variables will be investigated:

- Oxygen saturation (O2-sat, in room air) (only absolute, as relative already primary outcome)
- Respiratory rate (RR, in room air) (relative and absolute)

- Retractions (yes/no)
- Coughing (yes/no)
- Oxygen demand

- pO2, pCO2 (capillary, in room air)
- Chest x-ray
- Quality-of-life
- Health economics
- Overall survival
- Weight for height
- Cumulative amounts of steroid equivalents. Clinical course of lung disease (since last visit): Healthy/ Sick-better/ Sick-same/ Sick-worse/ Patient died
- Pulmonary exacerbation (since last visit)
If > 5y old (If a child ≤ 5 years is already able to perform the listed investigations (spirometry or bodyplethysmography), these should also be performed and documented at the discretion of the investigator.)
The following lung function parameters will be assessed:
FEV1 % predicted (recorded in L), FEV 1 (L), FVC % predicted (recorded in L), FVC (L); MEF 75 (L/s); MEF 50 (L/s); MEF 25 (L/s); TLC (L); ITGV (L); RV (L); R eff (kPa*s/L); R eff predicted (%).
reference values according to the GLI 2012 lung function regression equations

- 6 minute walking distance (meter)
- O2-saturation before and after 6MWT
- Borg scale

- If ventilated:
Duration (h) of mechanical ventilation
NO (%), ECMO yes/no, if yes VA/VV, double lumen vs. single lumen, Flow-rate.

- Safety monitoring
Adverse events, clinical laboratory values (GOT, Creatinine, gGT, blood count, differential, LDH, potassium, steady state drug level), ECG, ophthalmologic review

Cambio absoluto y cambio relativo, desde el día 1 del estudio (Visita 2) al día 28 para el bloque HCQ START, y desde el día 1 del estudio al día 84 (Visita 5) para el bloque HCQ STOP: cambio observado con tratamiento activo en comparación con el cambio observado con placebo. Se investigará el cambio en los siguientes parámetros:
• Saturación de oxígeno (sólo cambio absoluto, el cambio relativo es el criterio de valoración principal)
• Frecuencia respiratoria
• Retracciones, tos
• Demanda de oxígeno
• pO2, pCO2
• Radiografía de tórax
• Calidad de vida
• Economía de la salud
• Supervivencia global
• Peso por altura
• Cantidades acumulativas de equivalentes de esteroides
• Exacerbaciones pulmonares
Si el paciente tiene > 5 años:
• Parámetros de la espirometría o pletismografía corporal
• Test de la marcha de los 6 minutos (TM6M): distancia y saturación de O2 antes y después del test
• Escala de Borg
Parámetros de seguridad
• Acontecimientos adversos
• Parámetros de laboratorio
• Anormalidades en el ECG
• Anormalidades oftalmológicas

E.5.2.1

Timepoint(s) of evaluation of this end point

56 / 84 days

56 / 84 días

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

Yes

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

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

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

Austria

Italy

Poland

Portugal

Spain

Turkey

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

última visita, último paciente

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

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)

Yes

F.1.2.1

Number of subjects for this age range:

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

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

Subjects in this trial are mostly children, consent of both legally authorized representatives must be sought, Children who are able to understand nature, scope, and possible consequences of the clinical trial must also give their informed consent.

Los paciente son principalmente niños donde el consentimiento de ambos representantes legales debe de ser buscado. Aquellos que puedan entender la naturaleza, objetivo y posibles consecuencias del estudio deben de obtener un consentimiento informado.

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

F.4.2.2

In the whole clinical trial

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)

According to Standard- of-Care

De acuerdo a la práctica clínica habitual

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

2019-01-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-12-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-09-09

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Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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