Clinical Trials Register

Summary
EudraCT Number:	2022-001294-31
Sponsor's Protocol Code Number:	D5244C00001
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:	2022-09-19
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

2022-001294-31

A.3

Full title of the trial

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Patients with Eosinophilic Esophagitis (CROSSING)

Ensayo de fase III aleatorizado, doble ciego, de grupos paralelos, controlado con placebo, para evaluar la eficacia y seguridad de Tezepelumab en pacientes con Esofagitis Eosinofílica (CROSSING)

A.3.1

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

Efficacy and Safety of Tezepelumab in Patients with Eosinophilic Esophagitis

Eficacia y seguridad de Tezepelumab en pacientes con Esofagitis Eosinofílica

A.3.2

Name or abbreviated title of the trial where available

CROSSING

A.4.1

Sponsor's protocol code number

D5244C00001

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	AstraZeneca AB
B.1.3.4	Country	Sweden
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	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca Farmacéutica Spain, S.A.
B.5.2	Functional name of contact point	Unidad de Investigación Clínica
B.5.3	Address:
B.5.3.1	Street Address	C/ Serrano Galvache, 56; Parque Norte, Ed. Álamo
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28033
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34900200444
B.5.6	E-mail	informacionEECC-Spain@astrazeneca.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	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	Tezepelumab via APFS
D.3.2	Product code	MEDI9929 anti-TSLP mAb (AMG157)
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tezepelumab
D.3.9.1	CAS number	1572943-04-4
D.3.9.2	Current sponsor code	MEDI9929
D.3.9.3	Other descriptive name	AMG 157
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	99 to 121
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal Antibody

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	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous 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 (EoE) is a rare, chronic inflammatory disorder triggered by an immune response to foods and aeroantigens and characterized by a combination of esophageal dysfunction and eosinophilic infiltration of the esophagus

La esofagitis eosinofílica (EoE) es un trastorno inflamatorio crónico raro desencadenado por una respuesta inmunitaria a los alimentos y aeroantígenos y caracterizado por una combinación de disfunción esofágica e infiltración eosinofílica del esófago.

E.1.1.1

Medical condition in easily understood language

Eosinophilic esophagitis (EoE)
Allergic Esophagitis

Esofagitis eosinofílica (EoE)
Esofagitis alérgica

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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

1. To evaluate the effect of tezepelumab on the histologic response in adult and adolescent participants with symptomatic and histologically active EoE
2. To evaluate the effect of tezepelumab on symptom improvement in adult and adolescent participants with symptomatic and histologically active EoE

1. Evaluar el efecto de tezepelumab sobre la respuesta histológica en participantes adultos y adolescentes con EoE sintomática e
histológicamente activa.
2. Evaluar el efecto de tezepelumab sobre la mejoría de los síntomas en participantes adultos y adolescentes con EoE sintomática e
histológicamente activa.

E.2.2

Secondary objectives of the trial

1. To evaluate the effect of tezepelumab on the centrally-read EoE EREFS
2. To evaluate the effect of tezepelumab on the centrally-read EoE-HSS
3. To evaluate the long-term effect of tezepelumab on the histologic response
4. To evaluate the long-term effect of tezepelumab on symptom improvement
5. To evaluate the long-term effect of tezepelumab on the centrally-read EoE EREFS
6. To evaluate the effect of tezepelumab on achievement of clinico-histological remission
7. To evaluate the effect of tezepelumab on peak eosinophil count
8. To evaluate the effect of tezepelumab on EoE symptoms in adolescents
9. To evaluate the long-term effect of tezepelumab

1. Evaluar el efecto de tezepelumab sobre la EREFS de la EoE de lectura centralizada.
2. Evaluar el efecto de tezepelumab sobre el EoE-HSS de lectura centralizada.
3. Evaluar el efecto a largo plazo de tezepelumab sobre la respuesta histológica.
4. Evaluar el efecto a largo plazo de tezepelumab sobre la mejoría de los síntomas.
5. Evaluar el efecto a largo plazo de tezepelumab en la EREFS de la EoE de lectura centralizada.
6. Evaluar el efecto de tezepelumab sobre el logro de la remisión clínico-histológica.
7. Evaluar el efecto de tezepelumab sobre el recuento máximo de eosinófilos.
8. Evaluar el efecto de tezepelumab sobre los síntomas de la EoE en adolescentes.
9. Evaluar el efecto a largo plazo de tezepelumab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent.

2. Weight ≥ 40 kg at Visit 1

3. Established diagnosis of EoE with a previous EGD and esophageal biopsy confirming a diagnosis of EoE.

4. Participants who have symptomatic EoE as defined by a history of on average at least 2 episodes of dysphagia (any severity of food going down slowly or being stuck in the throat) per week in the 4 weeks prior to Visit 1.

5. Must remain on a stabilized diet for at least 8 weeks prior to Visit 1 and during the course of the study (stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups).

6. May be on any background PPI and/or STC, during the course of the study, as long as background medications have been stable for at least 8 weeks prior to the screening/run-in period (Visit 1) and there is agreement not to change background medication or dosage unless medically indicated, during the screening/run-in and treatment period.

7. Participants currently leukotriene inhibitors and/or steroid treatments for asthma or allergies that are inhaled or administered intranasally, must report a stable dose for at least 4 weeks prior to the screening/run-in period (Visit 1).

8. If a medication for EoE (including PPI and/or STC) is discontinued prior to the screening/run-in, there should be a washout period of at least 8 weeks prior to Visit 1. Discontinuation of any marketed biologic (monoclonal or polyclonal antibody) should have a washout period of 4 months or 5 half-lives prior to Visit 1, whichever is longer.

9. Participants must have previously documented standard of care treatment, which could include PPI and/or STC and/or diet.

1. El participante debe tener entre 12 y 80 años en el momento de firmar/asentir el consentimiento informado.

2. Peso ≥ 40 kg en la visita 1.

3. Diagnóstico establecido de EoE con una EGD (esofagogastroduodenoscopia) y biopsia esofágica previas que confirmen un diagnóstico de EoE.

4. Participantes que tienen EoE sintomática definida por un promedio de al menos 2 episodios de disfagia (cualquier nivel de gravedad de lentitud a la hora de tragar los alimentos o de que estos se queden atascados en la garganta) por semana en las 4 semanas anteriores a la visita 1.

5. Deben mantener una dieta estable durante al menos 8 semanas antes de la visita 1 y durante el transcurso del estudio (la dieta estable se define como la ausencia de inicio de dietas de eliminación de uno o múltiples grupos de alimentos o la reintroducción de grupos de alimentos previamente eliminados).

6. Puede estar en tratamiento de base con cualquier IBP (inhibidor de la bomba de protones) y/o CTD (corticoesteroide tópico deglutido) durante el transcurso del estudio, siempre que el tratamiento de base se haya mantenido estable durante al menos 8 semanas antes del período de selección/rodaje (visita 1) y haya un acuerdo de no cambiar la medicación de base ni la dosis, a menos que esté médicamente indicado, durante el período de selección/rodaje y tratamiento.

7. Los participantes que actualmente reciban tratamiento con inhibidores de leucotrienos y/o esteroides para el asma o las alergias que se inhalan o administran por vía intranasal deben informar de estar recibiendo una dosis estable durante al menos 4 semanas antes del período de selección/rodaje (visita 1).

8. Si se interrumpe el tratamiento con un medicamento para la EoE (incluidos IBP y/o CTD) antes de la selección/rodaje, debe haber un período de reposo farmacológico de al menos 8 semanas antes de la visita 1. La interrupción del tratamiento con cualquier producto biológico comercializado (anticuerpo monoclonal o policlonal) debe tener un período de reposo farmacológico de 4 meses o 5 semividas antes de la visita 1, lo que sea mayor.

9. Los participantes deben documentar haberse sometido previamente al tratamiento de referencia, que podría incluir IBP y/o CTD y/o dieta.

E.4

Principal exclusion criteria

1. Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, celiac disease, eosinophilic enteritis, colitis, diverticulitis, irritable bowel syndrome, or other clinically significant gastrointestinal conditions as per Investigator discretion.
2.Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening.
3. Use of a feeding tube, or having a pattern of not eating solid food daily.
4. Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count > 1500 eosinophils/μL
5. EGPA vasculitis
6. Esophageal dilation performed within 8 weeks prior to screening.

1. Otros trastornos gastrointestinales, como infección activa por Helicobacter pylori, antecedentes de acalasia, varices esofágicas, enfermedad de Crohn, colitis ulcerosa, enfermedad inflamatoria intestinal, celiaquía, enteritis eosinofílica, colitis, diverticulitis, síndrome del intestino irritable u otras afecciones gastrointestinales clínicamente significativas a juicio del investigador.

2.Estenosis esofágica que impide el paso fácil de un endoscopio estándar o cualquier estenosis esofágica crítica que requiera dilatación en la selección.

3. Uso de una sonda de alimentación o tener un patrón de no comer alimentos sólidos a diario.

4. Síndrome hipereosinofílico, definido por afectación de múltiples órganos y recuento persistente de eosinófilos en sangre >1500 eosinófilos/µl.

5. Vasculitis de tipo EGPA.

6. Dilatación esofágica realizada en las 8 semanas anteriores a la selección.

E.5 End points

E.5.1

Primary end point(s)

1. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels at Week 24
2. Change from baseline in DSQ score at Week 24

1. Respuesta histológica de recuento máximo de eosinófilos esofágicos por HPF de ≤6 en todos los niveles esofágicos disponibles en la semana 24.
2. Variación respecto al inicio en la puntuación DSQ en la semana 24.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Week 24
2. Week 24

1. Semana 24
2. Semana 24

E.5.2

Secondary end point(s)

1. Change from baseline in EoE EREFS at Week 24 and Week 52

2. Change from baseline in EoE-HSS grade score at Week 24 and Week 52

3. Change from baseline in EoE-HSS stage score at Week 24 and Week 52

4. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels at Week 52

5. Change from baseline in DSQ score at Week 52

6. Response of achieving clinico-histological remission at Week 24 and Week 52

7. Change from baseline in peak esophageal eosinophil count (EOS/HPF) at Week 24 and Week 52

8. Changes from baseline in PEESS Module at Week 24 and Week 52 (adolescents only)

1. Variación respecto al inicio en la escala EREFS de EoE en la semana 24 y la semana 52.

2. Variación respecto al inicio en la puntuación del grado HSS de EoE en la semana 24 y la semana 52.

3. Variación respecto al inicio en la puntuación del estadio HSS de EoE en la semana 24 y la semana 52.

4. Respuesta histológica de recuento máximo de eosinófilos esofágicos por HPF de ≤6 en todos los niveles esofágicos disponibles en la semana 52.

5. Variación respecto al inicio en la puntuación DSQ en la semana 52.

6. Respuesta para lograr la remisión clínico-histológica en la semana 24 y la semana 52.

7. Variación respecto al inicio en el recuento máximo de eosinófilos esofágicos (EOS/HPF) en la semana 24 y la semana 52.

8. Variación respecto al inicio en el módulo PEESS en la semana 24 y la semana 52 (solo adolescentes).

E.5.2.1

Timepoint(s) of evaluation of this end point

Varies depending on the endpoint/objective

Varía en función del criterio de valoración / objetivo

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

Yes

E.6.7

Pharmacodynamic

Yes

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

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

Australia

Brazil

Canada

China

Israel

Japan

New Zealand

United States

Austria

Finland

Sweden

Netherlands

Spain

Czechia

Germany

Greece

Italy

Belgium

Denmark

Norway

Slovakia

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

LSLV

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:

314

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

211

F.4.2.2

In the whole clinical trial

360

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)

After completion of the treatment period, participants will be eligible to participate in an active treatment extension period (lasting for a minimum of 24 weeks), followed by a 12-week off-treatment safety follow-up period. Participants who will not participate in the extension period will participate in a 12-week off-treatment safety follow-up period following completion of the 52-week treatment period

Tras completar el periodo de tratamiento, los pacientes podrán ser elegidos para participar en un periodo de extensión del tratamiento (con una duración mínima de 24 semanas), seguido de un período de seguimiento de la seguridad de 12 semanas sin tratamiento. Los participantes que no participen en el período de ampliación participarán en un período de seguimiento de la seguridad de 12 semanas sin tratamiento después de completar el período de tratamiento de 52 semanas.

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

2023-01-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-26

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

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