Clinical Trials Register

Summary
EudraCT Number:	2017-003516-39
Sponsor's Protocol Code Number:	BUL-3/EER
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:	2021-06-14
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

2017-003516-39

A.3

Full title of the trial

Double-blind, randomized phase III trial in adult and adolescent patients with eosinophilic esophagitis to prove superiority compared to placebo of an episodic and/or a continuous 48-week treatment with budesonide orodispersible tablets for maintaining clinico-histological remission

Ensayo de fase III, aleatorizado, doble ciego en pacientes adultos y adolescentes con esofagitis eosinofílica para demostrar la superioridad en comparación con placebo de un tratamiento ocasional y/o continuo de 48 semanas con comprimidos bucodispersables de budesonida para el mantenimiento de una remisión clínico-histológica

A.3.1

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

A phase III clinical study in adult and adolescent patients with eosinophilic inflammation of the gullet to prove superiority compared to placebo of an episodic and/or a continuous 48-week treatment with budesonide orodispersible tablets for maintaining remission

Un ensayo clínico fase III en pacientes adultos y adolescentes con inflamación eosinofílica del esófago para demostrar la superioridad en comparación con placebo de un tratamiento ocasional y/o continuo de 48 semanas con comprimidos bucodispersables de budesonida para el mantenimiento de la remisión

A.4.1

Sponsor's protocol code number

BUL-3/EER

A.5.4

Other Identifiers

Name:

EOS-3

Number:

Acronym

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	Dr. Falk Pharma GmbH
B.1.3.4	Country	Germany
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	Dr. Falk Pharma GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SERMES PLANIFICACION S.L
B.5.2	Functional name of contact point	START UP UNIT
B.5.3	Address:
B.5.3.1	Street Address	Calle Rufino González, 14-2º D
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28037
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3491327 50 25
B.5.5	Fax number	+3491754 27 21
B.5.6	E-mail	start-up@sermescro.com

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	Jorveza 1 mg orodispersible tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Dr. Falk Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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/3/13/1181
D.3 Description of the IMP
D.3.1	Product name	Budesonide 1 mg orodispersible tablets
D.3.2	Product code	BUL 1 mg
D.3.4	Pharmaceutical form	Orodispersible tablet
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	BUDESONIDE
D.3.9.1	CAS number	51333-22-3
D.3.9.4	EV Substance Code	SUB05955MIG
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	1
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	Yes
D.2.1.1.1	Trade name	Jorveza 0.5 mg orodispersible tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Dr. Falk Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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/3/13/1181
D.3 Description of the IMP
D.3.1	Product name	Budesonide 0.5 mg orodispersible tablets
D.3.2	Product code	BUL 0.5 mg
D.3.4	Pharmaceutical form	Orodispersible tablet
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	BUDESONIDE
D.3.9.1	CAS number	51333-22-3
D.3.9.4	EV Substance Code	SUB05955MIG
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	0.5
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Orodispersible tablet
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

Maintenance of remission in eosinophilic esophagitis

Mantenimiento de la remisión en la esofagitis eosinofílica

E.1.1.1

Medical condition in easily understood language

Chronic allergic/immune-mediated inflammatory disease of the gullet in its remission phase

Enfermedad inflamatoria crónica alérgica/inmune del esófago en su fase de remisión

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10064220
E.1.2	Term	Eosinophilic esophagitis
E.1.2	System Organ Class	100000004856

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 prove superiority compared to placebo of episodic treatment with 4 cycles of budesonide 0.5 mg orodispersible tablets twice daily (BID) for 4 weeks followed by 8 weeks placebo BID over a total of 48 weeks and/or of continuous 48-week treatment with budesonide 0.5 mg orodispersible tablets BID in adult and adolescent eosinophilic esophagitis (EoE) patients in maintaining clinico-histological remission.

Demostrar la superioridad en comparación con el placebo del tratamiento ocasional con 4 ciclos de comprimidos bucodispersables de 0,5 mg de budesonida dos veces al día (2v/d) durante 4 semanas seguido de 8 semanas de placebo 2v/d durante un total de 48 semanas y/o de 48 semanas de tratamiento continuo con comprimidos bucodispersables de 0,5 mg de budesonida 2v/d en pacientes adultos y adolescentes con esofagitis eosinofílica (EEo) para mantener una remisión clínico-histológica

E.2.2

Secondary objectives of the trial

Double-blind maintenance phase:
• To further assess EoE-associated clinical, endoscopic and histological findings after 48 weeks treatment for maintenance of remission,
• To study safety and tolerability as assessed by adverse events and laboratory parameters,
• To assess patients’ quality of life.

Fase de mantenimiento con doble ciego:
• Evaluar más a fondo los hallazgos clínicos, endoscópicos e histológicos asociados con la EEo después de 48 semanas de tratamiento para el mantenimiento de una remisión,
• Estudiar la seguridad y la tolerabilidad mediante la evaluación de los acontecimientos adversos y los parámetros analíticos,
• Evaluar la calidad de vida de los pacientes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Signed informed consent,
• Male or female patients, 16 to 75 years of age,
• Confirmed clinico-histological diagnosis of EoE according to established diagnostic criteria,
• Clinico-histological remission of EoE,
• Negative pregnancy test in females of childbearing potential at baseline visit

• Consentimiento informado firmado,
• Pacientes masculinos o femeninos, de 16 a 75 años de edad,
• Diagnóstico clínico-histológico confirmado de EEo según los criterios diagnósticos establecidos,
• Remisión clínico-histológica de EEo,
• Prueba de embarazo negativa en mujeres en edad fértil en la visita de seleccíón.

E.4

Principal exclusion criteria

• Gastroesophageal reflux disease (GERD),
• Achalasia, scleroderma esophagus, or systemic sclerosis,
• Clinically evident causes for esophageal eosinophilia other than EoE,
• Any concomitant esophageal disease and relevant active gastrointestinal disease,
• Abnormal laboratory values, presence of or suspected relevant concomitant disease(s), that could affect study-specific assessments and/or their evaluation, or might compromise patient's safety and/or compliance (e.g. severe cardiovascular, renal, endocrine, psychiatric diseases/disorders, relevant infectious diseases associated with clinical signs, liver cirrhosis, portal hypertension, or uncontrolled cardiovascular disease, diabetes mellitus, osteoporosis, active peptic ulcer disease, glaucoma, cataract,
• History of cancer, recent upper gastrointestinal bleeding, esophageal surgery, esophageal dilation procedures or need for an immediate endoscopic intervention due to a stricture
• Diagnosis of chickenpox, herpes zoster, or measles within the last 3 months prior to baseline,
• Treatment with medication, that could compromise/influence the effects of the study treatment, assessment of the endpoints and/or patients' safety, during or within too narrow timeframe of the clinical trial (e.g. systemic or oral glucocorticosteroids, immunosuppressants, CYP3A4 inhibitors, live vaccination, treatment with proton pump inhibitors, consumption of grapefruit)
• Existing or intended pregnancy or breast-feeding.

• Enfermedad por reflujo gastroesofágico (ERGE),
• Acalasia, esclerodermia esofágica o esclerosis sistémica,
• Causas clínicamente evidentes de eosinofilia esofágica distintas de la EEo,
• Cualquier enfermedad esofágica concomitante y enfermedad gastrointestinal activa relevante,
• Valores de laboratorio anormales, presencia o sospecha de enfermedad(es) concomitante(s) relevante(s), que pueda(n) afectar a las valoraciones específicas del estudio y/o a su evaluación, o que puedan comprometer la seguridad y/o el cumplimiento del paciente (por ejemplo, enfermedades/trastornos cardiovasculares, renales, endocrinos, psiquiátricos graves, enfermedades infecciosas relevantes asociadas a signos clínicos, cirrosis hepática, hipertensión portal, o enfermedad cardioascular no controlada, diabetes mellitus, osteoporosis, úlcera péptica activa, glaucoma, cataratas)
• Antecedentes de cáncer, hemorragia gastrointestinal superior reciente, cirugía esofágica, procedimientos de dilatación esofágica o necesidad de una intervención endoscópica inmediata debido a una estenosis,
• Diagnóstico de varicela, herpes zóster o sarampión en los últimos 3 meses antes del inicio,
• Tratamiento con medicación que pueda comprometer/influir en los efectos del tratamiento del estudio, en la evaluación de los criterios de valoración y/o en la seguridad de los pacientes, durante o dentro de un plazo demasiado estrecho del ensayo clínico (por ejemplo, glucocorticosteroides sistémicos u orales, inmunosupresores, inhibidores del CYP3A4, vacunación viva, tratamiento con inhibidores de la bomba de protones, consumo de pomelo),
• Embarazo o lactancia existente o previsto.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients free of treatment failure after a 48 weeks DB treatment phase

Proporción de pacientes sin fracaso del tratamiento después de una fase de tratamiento DC de 48 semanas

E.5.1.1

Timepoint(s) of evaluation of this end point

after 48 weeks of double-blind phase

Después de 48 semanas de la fase doble ciego

E.5.2

Secondary end point(s)

• Proportion of patients with histological relapse at DB week 48
• Proportion of patients with clinical relapse, or who have experienced a food impaction, which needed endoscopic intervention during the DB treatment phase
• Proportion of patients in clinico-histological remission at DB week 48

• Proporción de pacientes con recidiva histológica en la semana 48 de DC
• Proporción de pacientes con una recidiva clínica, o que hayan sufrido una impactación de alimentos que haya necesitado una intervención endoscópica durante la fase de tratamiento de DC
• Proporción de pacientes en remisión clínico-histológica en la semana 48 de DC

E.5.2.1

Timepoint(s) of evaluation of this end point

after 48 weeks of double-blind phase

Después de 48 semanas de la fase doble ciego

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

Yes

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

Yes

E.8.1.7.1

Other trial design description

Abierto: posibles fases de 6 semanas para la inducción o reinducción de la remisión

Open-label: possible 6-week phases for induction or re-induction of remission

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

Germany

Italy

Spain

Switzerland

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

Ultima 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)

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.4.2.2

In the whole clinical trial

110

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)

Treatment after trial end (i.e., after FU [follow-up visit]) is left to the investigator’s discretion.

El tratamiento después de la finalización del ensayo (es decir, después de la visita de seguimiento) se deja a discreción del investigador.

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

2021-07-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-30

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

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