Clinical Trials Register

Summary
EudraCT Number:	2013-004282-14
Sponsor's Protocol Code Number:	GA29103
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-08-06
Trial results	View 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

2013-004282-14

A.3

Full title of the trial

PHASE III, RANDOMIZED, MULTICENTER DOUBLE-BLIND, DOUBLE-DUMMY STUDY TO EVALUATE THE EFFICACY AND SAFETY OF
ETROLIZUMAB COMPARED WITH INFLIXIMAB IN PATIENTS WITH MODERATE TO SEVERE ACTIVE ULCERATIVE COLITIS WHO ARE NAIVE TO TNF INHIBITORS

ESTUDIO DE FASE III, ALEATORIZADO, MULTICÉNTRICO, DOBLE CIEGO, CON DOBLE SIMULACIÓN, PARA EVALUAR LA EFICACIA Y SEGURIDAD DE ETROLIZUMAB COMPARADO CON INFLIXIMAB EN PACIENTES CON COLITIS ULCEROSA ACTIVA ENTRE MODERADA E INTENSA QUE NO HAN RECIBIDO TRATAMIENTO PREVIO CON INHIBIDORES DEL TNF

A.3.1

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

A study of the effectiveness (efficacy) and safety of etrolizumab compared with infliximab in ulcerative colitis patients who have not previously received TNF inhibitors

ESTUDIO PARA EVALUAR LA EFICACIA Y SEGURIDAD DE ETROLIZUMAB COMPARADO CON INFLIXIMAB EN PACIENTES CON COLITIS ULCEROSA QUE NO HAN RECIBIDO TRATAMIENTO PREVIO CON INHIBIDORES DEL TNF

A.4.1

Sponsor's protocol code number

GA29103

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02136069

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	Roche Farma S.A. en nombre de F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	34 91 3257 300
B.5.6	E-mail	global.rochegenentechtrials@roche.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	Etrolizumab
D.3.2	Product code	Ro 549-0261/F04
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	Etrolizumab
D.3.9.1	CAS number	1044758-60-2
D.3.9.2	Current sponsor code	RO5490261
D.3.9.3	Other descriptive name	ETROLIZUMAB
D.3.9.4	EV Substance Code	SUB75320
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	105
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	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	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	Humanized monoclonal antibody
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	Remicade
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen Biologics B.V., The Netherlands
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLIXIMAB
D.3.9.1	CAS number	170277-31-3
D.3.9.2	Current sponsor code	RO6897845
D.3.9.4	EV Substance Code	SUB02681MIG
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	100
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	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	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
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ulcerative Colitis

Colitis ulcerosa

E.1.1.1

Medical condition in easily understood language

A form of inflammatory bowel disease

Un tipo de enfermedad inflamatoria intestinal

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	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of etrolizumab compared with infliximab for sustained remission at Weeks 10, 30, and 54 in patients with ulcerative colitis

Evaluar la eficacia de etrolizumab en comparación con infliximab para la remisión sostenida en las semanas 10, 30 y 54 en pacientes con colitis ulcerosa

E.2.2

Secondary objectives of the trial

? To evaluate remission at Week 10.
? To evaluate remission at Week 54.
? To evaluate sustained clinical remission at Weeks 10, 30, and 54.
? To evaluate clinical response at Week 10.
? To evaluate sustained clinical response at Weeks 10, 30 and 54.
? To evaluate clinical remission at Week 54.
? To evaluate the overall safety and tolerability of etrolizumab over a period of 54 weeks.

? Evaluar la remisión en la semana 10.
? Evaluar la remisión en la semana 54.
? Evaluar la remisión clínica sostenida en las semanas 10, 30 y 54.
? Evaluar la respuesta clínica en la semana 10.
? Evaluar la respuesta clínica sostenida en las semanas 10, 30 y 54
? Evaluar la remisión clínica en la semana 54
? Evaluar la seguridad y tolerabilidad generales de etrolizumab durante un período de 54 semanas

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- 18-80 years of age, inclusive.
- Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
- Naive to treatment with any anti-TNF therapy
- An inadequate response to or intolerance of prior corticosteroid and/or immunosuppressant treatment
- Background regimen for UC may include oral 5-ASA, oral corticosteroids, budenoside MMX, probiotics, AZA, 6-MP, or MTX if doses have been stable during the screening period
- Use of highly effective contraception as defined by the protocol

? Tener entre 18 y 80 años de edad, ambos inclusive
? Diagnóstico de CU activa entre moderada e intensa, según lo determinado mediante una MCS
? No haber recibido ningún tratamiento previo contra el TNF
? Los pacientes deben haber tenido una respuesta inadecuada, una pérdida de respuesta o una intolerancia a un tratamiento previo con inmunosupresores y/o corticoesteroides.
? El tratamiento previo contra la CU puede incluir 5-ASA, corticoesteroides por vía oral, MMX de budesonida, probióticos, AZA, 6-MP o MTX, siempre que las dosis se hayan mantenido estable durante el periodo de screening
? Uso de método anticonceptivo de alta eficacia según se define en el protocolo

E.4

Principal exclusion criteria

- A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic colitis,
radiation colitis, or microscopic colitis, Crohn's disease, fistulas or abdominal abscesses, colonic mucosal dysplasia, intestinal obstruction, toxic megacolon, or unremoved adenomatous colonic polyps
- Prior or planned surgery for UC.
- Past or present ileostomy or colostomy.
- Have received non-permitted inflammatory bowel disease (IBD) therapies (including natalizumab, vedolizumab, and efalizumab) as stated in the protocol
- Chronic hepatitis B or C infection, HIV or tuberculosis (active or latent).

? Antecedentes o condición y enfermedades actuales que afecten al tracto digectivo, como colitis indeterminada, sospecha de colitis isquémica, colitis por radiación, o colitis microscopica, enfermedad de Crohn, fístula o absceso abdominal, displasia de la mucosa del colon, alguna constricción (estenosis) del colon, megacolon tóxico, o pólipos
adenomatosos del colon que no se han eliminado
? Operación quirúrgica anterior o prevista para la CU
? Ileostomía o colostomía anterior o presente
? Haber recibido tratamiento no permitido para la enfermedad inflamatoria intestinal incluidos natalizumab, vedolizumab y efalizumab) tal como se describe en el protocolo
? Infección por hepatitis B o C crónica, VIH, o tuberculosis (activa o latente)

E.5 End points

E.5.1

Primary end point(s)

Sustained clinical remission as determined by Mayo clinic score (MCS)

Remisión clínica sostenida determinada mediante la puntuación de la clínica Mayo (MCS)

E.5.1.1

Timepoint(s) of evaluation of this end point

At Weeks 10, 30, and 54

Semanas 10, 30 y 54

E.5.2

Secondary end point(s)

1) Remission
2) Clinical remission
3) Sustained clinical remission
4) Sustained clinical response
5) Clinical response

1) Remisión
2) Remisión clínica
3) Remisión clínica sostenida
4) Respuesta clínica sostenida
5) Respuesta clínica

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Weeks 10 and 54
2) week 54
3) Weeks 10, 30 and 54
4) Weeks 10, 30 and 54
5) week 10

1) Semanas 10 y 54
2) Semana 54
3) Semanas 10, 30 y 54
4) Semanas 10, 30 y 54
5) Semana 10

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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability, exploratory biomarkers

Tolerabilidad , biomarcadores exploratorios

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

doble enmascaramiento

Double-dummy

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

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

130

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

Belgium

Canada

Czech Republic

Germany

Hungary

Israel

Italy

Korea, Republic of

Netherlands

Norway

Philippines

Portugal

Romania

Singapore

South Africa

Spain

Sweden

Switzerland

United Kingdom

Vietnam

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

The end of the study is defined as the last patient last safety follow-up visit in this protocol, or last patient enrolled in to the OLE-SM study, whichever is later.

El final del estudio se define como la última visita de seguimiento de la seguridad del último paciente de este protocolo o, si ocurre más tarde, el último paciente inscrito en el estudio de OLE-SM.

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

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:

698

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

481

F.4.2.2

In the whole clinical trial

720

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)

Patients with disease worsening, patients who receive defined rescue treatment, patients who complete 54 wks of the study, will transfer to the Open Label Extension (OLE, Part 1) of the OLE-Safety Monitoring (SM) study where, if eligible, they receive OL etrolizumab treatment.
Patients not enrolling to Part 1 of OLE-SM study will enter a 12 wk safety FU phase after the last dose of study medication. They will then enroll into the SM (Part 2) of the OLE-SM for FU for PML for additional 92 wks.

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

2014-11-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-06-23

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