Clinical Trials Register

Summary
EudraCT Number:	2017-003516-39
Sponsor's Protocol Code Number:	BUL-3/EER
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-08-17
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

Italy - Italian Medicines Agency

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

Studio in doppio cieco, randomizzato di fase III, in pazienti adulti e adolescenti affetti da esofagite eosinofila per comprovare la superiorità confrontata con il placebo di un trattamento episodico e/o continuo di 48 settimane con budesonide compresse orodispersibili per il mantenimento della remissione clinico-istologica

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

Studio clinico di fase III in pazienti adulti e adolescenti affetti da esofagite eosinofila per comprovare la superiorità confrontata con il placebo di un trattamento episodico e/o continuo di 48 settimane con budesonide compresse orodispersibili per il mantenimento della remissione

A.3.2

Name or abbreviated title of the trial where available

Episodic and continuous treatment with budesonide orodispersible tablets versus placebo for maintena

Trattamento episodico e continuo con budesonide compresse orodispersibili versus placebo per il mant

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	Dr. Falk Pharma GmbH
B.5.2	Functional name of contact point	Dept. of Clinic. Res. & Development
B.5.3	Address:
B.5.3.1	Street Address	Leinenweberstr. 5
B.5.3.2	Town/ city	Freiburg
B.5.3.3	Post code	79108
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4976115140
B.5.5	Fax number	+497611514377
B.5.6	E-mail	zentrale@drfalkpharma.de

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 compresse orodispersibili
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	Germany
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 compresse orodispersibili
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.3.9.2	Current sponsor code	Not applicable
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	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: 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 compresse orodispersibili
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	Germany
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 compresse orodispersibili
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.3.9.2	Current sponsor code	Not applicable
D.3.9.4	EV Substance Code	SUB05955MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	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

Mantenimento della remissione della esofagite eosinofila

E.1.1.1

Medical condition in easily understood language

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

Malattia allergica cronica / infiammatoria immunomediata dell'esofago nella sua fase di remissione

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.

comprovare la superiorità, confrontata con il placebo, di un trattamento episodico con 4 cicli di budesonide 0,5 mg compresse orodispersibili due volte al giorno (BID) per 4 settimane, seguiti da 8 settimane di placebo BID, per un totale di 48 settimane, e/o di un trattamento continuo di 48 settimane con budesonide 0,5 mg compresse orodispersibili BID in pazienti adulti e adolescenti affetti da esofagite eosinofila (EoE) per il mantenimento della remissione clinico-istologica

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 di mantenimento in doppio cieco:
• valutare ulteriormente i risultati clinici, endoscopici e istologici associati all’EoE dopo 48 settimane di trattamento per il mantenimento della remissione;
• studiare la sicurezza e la tollerabilità, valutate in base a eventi avversi e parametri di laboratorio;
• valutare la qualità di vita dei pazienti.

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

• consenso informato firmato
• pazienti di sesso maschile o femminile, di età compresa tra 16 e 75 anni
• diagnosi clinico-istologica confermata di EoE, in base a criteri diagnostici stabiliti
• remissione clinico-istologica di EoE
• test di gravidanza negativo per le pazienti di sesso femminile potenzialmente fertili alla visita basale

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.

• malattia da reflusso gastroesofageo (MRGE)
• acalasia, sclerodermia dell’esofago o sclerosi sistemica
• cause con evidenza clinica di eosinofilia esofagea diverse dall’EoE
• malattie esofagee concomitanti e malattia attiva gastrointestinale rilevante
• valori di laboratorio anormali, presenza o sospette malattie concomitanti rilevanti, che potrebbero influenzare le valutazioni specifiche dello studio e / o la loro valutazione, o potrebbero compromettere la sicurezza e / o la compliance del paziente (ad es. Gravi malattie / disturbi cardiovascolari, renali, endocrini, psichiatrici , malattie infettive rilevanti associate a segni clinici, cirrosi epatica, ipertensione portale o malattia cardiovascolare non controllata, diabete mellito, osteoporosi, ulcera peptica attiva, glaucoma, cataratta)
• anamnesi di cancro, recente emorragia del tratto gastrointestinale superiore, chirurgia esofagea, procedure di dilatazione esofagea o necessità di un intervento endoscopico immediato a causa di una stenosi
• diagnosi di varicella, herpes zoster o morbillo nei 3 mesi precedenti alla visita basale
• trattamento con farmaci che potrebbero compromettere / influenzare gli effetti del trattamento in studio, la valutazione degli endpoint e / o la sicurezza dei pazienti, durante o entro un arco di tempo troppo ristretto dello studio clinico (ad es. Glucocorticosteroidi sistemici o orali, immunosoppressori, inibitori del CYP3A4, vaccino vivo attenuato, trattamento con inibitori della pompa protonica, consumo di pompelmo)
• gravidanza e allattamento, in corso o previsti

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

proporzione di pazienti senza fallimento del trattamento dopo una fase di trattamento in doppio cieco di 48 settimane

E.5.1.1

Timepoint(s) of evaluation of this end point

after 48 weeks of double-blind phase

dopo 48 settimane dalla fase in doppio cieco

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

• proporzione di pazienti con recidiva istologica alla settimana 48 in doppio cieco
• proporzione di pazienti con recidiva clinica, o che hanno riferito un’ostruzione da bolo alimentare che ha richiesto intervento endoscopico durante la fase di trattamento in doppio cieco
• proporzione di pazienti in remissione clinico-istologica alla settimana 48 in doppio cieco

E.5.2.1

Timepoint(s) of evaluation of this end point

after 48 weeks of double-blind phase

dopo 48 settimane dalla fase in doppio cieco

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

In aperto: possibili fasi di 6 settimane per la induzione o la re-induzione della remissione

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

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

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

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:

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.

Il trattamento dopo la fine dello studio (cioè dopo FU [visita di follow-up]) è lasciato alla discrezione dello sperimentatore.

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

2021-07-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-29

P. End of Trial
P.	End of Trial Status	Completed

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