Clinical Trials Register

Summary
EudraCT Number:	2020-001314-37
Sponsor's Protocol Code Number:	BUL-8/EEA
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-02-12
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

Portugal - INFARMED

A.2

EudraCT number

2020-001314-37

A.3

Full title of the trial

Double-blind, double-dummy, randomized, parallel-group, non-inferiority phase III trial on the efficacy and tolerability of 2 mg once daily vs. 1 mg twice daily budesonide orodispersible tablets for induction of histological remission in adults with eosinophilic esophagitis

Ensaio duplo-cego, duplo simulado, randomizado, grupo paralelo, não-inferioridade fase III sobre a eficácia e tolerabilidade de 2 mg uma vez pordia contra 1 mg duas vezes por dia de orodispersíveis de budesonida paraindução de remissão histológica em adultos com esofagite eosinofílica

A.3.1

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

Clinical study to show equal clinical efficacy of two dosing regimen of budesonid orodispersible tablets (twice daily vs. once daily) for treatment of inflammation of the esophagus

Estudo clínico para mostrar igual eficácia clínica de dois regimes de dosagem de orodispersíveis de budesonida (duas vezes por dia vs. uma vez por dia) para o tratamento da inflamação do esófago

A.3.2

Name or abbreviated title of the trial where available

Once daily versus twice daily budesonide orodispersible tablets for induction of remission in EoE

Comprimidos orodispersíveis de budesonida 1 ou 2 vezes por dia para indução de remissão em EoE

A.4.1

Sponsor's protocol code number

BUL-8/EEA

A.5.4

Other Identifiers

Name:

Acronym by sponsor

Number:

EOS-4

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 Clinical R&D
B.5.3	Address:
B.5.3.1	Street Address	Leinenweberstraße 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	+497611514193
B.5.5	Fax number	+497611514377
B.5.6	E-mail	sarah.burrack@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	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/3/13/1181
D.3 Description of the IMP
D.3.1	Product name	Budesonide 2 mg orodispersible tablets (BUL 2 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	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	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	Comparator
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.3.4	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.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

eosinophilic esophagitis

esofagite eosinofílica

E.1.1.1

Medical condition in easily understood language

allergy-like, chronic inflammation of the esophagus

inflamação crónica e alérgica do esófago

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	PT
E.1.2	Classification code	10064212
E.1.2	Term	Eosinophilic oesophagitis
E.1.2	System Organ Class	10017947 - Gastrointestinal 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

To prove the non-inferiority of 1 x 2 mg/d vs. 2 x 1 mg/d budesonide orodispersible tablets for the induction of histological remission in adult patients with active eosinophilic esophagitis (EoE)

Provar a não-inferioridade de 1 x 2 mg/d vs. 2 x 1 mg/d comprimidos orodispersíveis de budesonida para a indução da remissão histológica em doentes adultos com esofagite eosinófila activa (EoE)

E.2.2

Secondary objectives of the trial

- To further assess EoE-associated clinical, endoscopic, and histological findings after 6 weeks treatment with budesonide orodispersible tablets,
- To study safety and tolerability as assessed by adverse events and laboratory parameters,
- To assess patients’ quality of life

- Avaliar melhor os resultados clínicos, endoscópicos e histológicos associados à EoE após 6 semanas de tratamento com comprimidos orodispersíveis de budesonida,
- Estudar a segurança e tolerabilidade avaliada por eventos adversos e parâmetros laboratoriais,
- Avaliar a qualidade de vida dos doentes

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Signed informed consent,
- Man or woman 18 to 75 years of age,
- Confirmed diagnosis of eosinophilic esophagitis (EoE)
- Active symptomatic and histological EoE
- At least 4 points in Patient’s Global Assessment (PatGA) concerning the severity of EoE symptoms at baseline visit,

- Consentimento informado assinado,
- Homem ou mulher dos 18 aos 75 anos de idade,
- Diagnóstico confirmado de esofagite eosinófila (EoE)
- EoE activo sintomático e histológico
- Pelo menos 4 pontos na Avaliação Global do Paciente (PatGA) relativamente à gravidade dos sintomas da EoE na visita de base

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 gastro-intestinal 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 organic or psychiatric diseases/disorders, infectious diseases associated with clinical signs, liver cirrhosis, portal hypertension, cardiovascular disease, diabetes mellitus, osteoporosis, active peptic ulcer disease
- History of cancer, 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. immunosuppressants, CYP3A4 inhibitors, live vaccination, non-stable treatment with proton pump inhibitors)
- Exiting or intended pregnancy or breast-feeding

- Doença do refluxo gastroesofágico (DRGE),
- Achalasia, esclerodermia esofágica, ou esclerose sistémica,
- Causas clinicamente evidentes para a eosinofilia esofágica que não a EoE
- Qualquer doença concomitante do esófago e doença gastro-intestinal activa relevante
- Valores laboratoriais anormais, presença ou suspeita de doença(s) concomitante(s) relevante(s), que possam afectar avaliações específicas do estudo e/ou a sua avaliação, ou que possam comprometer a segurança e/ou a conformidade do doente (por exemplo, doenças/perturbações orgânicas ou psiquiátricas graves, doenças infecciosas associadas a sinais clínicos, cirrose hepática, hipertensão portal, doença cardiovascular, diabetes mellitus, osteoporose, úlcera péptica activa
- História de cancro, hemorragia gastrointestinal, cirurgia do esófago, procedimentos de dilatação esofágica ou necessidade de uma intervenção endoscópica imediata devido a uma estricção
- Diagnóstico de varicela, herpes zoster, ou sarampo nos últimos 3 meses antes da linha de base,
- Tratamento com medicamentos, que poderia comprometer/influenciar os efeitos do tratamento em estudo, avaliação dos pontos finais e/ou segurança dos pacientes, durante ou dentro de um prazo demasiado curto do ensaio clínico (por exemplo, imunossupressores, inibidores de CYP3A4, vacina viva, tratamento não estável com inibidores de bomba de protões)
- Gravidez ou amamentação em curso ou prevista

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with histological remission

Proporção de pacientes com remissão histológica

E.5.1.1

Timepoint(s) of evaluation of this end point

week 6

semana 6

E.5.2

Secondary end point(s)

1. Change in the peak eos/mm2 hpf from baseline to week 6 (LOCF),

2. Change in the severity of dysphagia

3. Change in the severity of odynophagia

4. Change of overall severity of EoE symptoms

5. Change in the total weekly Eosinophilic Esophagitis Activity Index

1. Alteração do pico eos/mm2 hpf da linha de base para a semana 6 (LOCF),

2. Alteração da gravidade da disfagia

3. Mudança na severidade da odinofagia

4. Alteração da gravidade geral dos sintomas da EoE

5. Mudança no índice semanal total de actividade de esofagite eosinófila

E.5.2.1

Timepoint(s) of evaluation of this end point

week 6 (for secondary endpoints 1 - 5)

semana 6 (para os pontos finais secundários 1 - 5)

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)

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)

Yes

E.8.2.2

Placebo

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

Yes

E.8.4

The trial involves multiple sites in the 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

Switzerland

Canada

Russian Federation

Austria

Germany

Portugal

Spain

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

UVUP

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

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

196

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

202

F.4.2.2

In the whole clinical trial

242

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)

The sponsor will provide the trial medication for compassionate use.

O promotor fornecerá o medicamento experimental para uso compassivo.

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

2021-06-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-26

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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