Clinical Trials Register

Summary
EudraCT Number:	2014-003824-36
Sponsor's Protocol Code Number:	GA29144
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-05-27
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2014-003824-36

A.3

Full title of the trial

A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF
ETROLIZUMAB AS AN INDUCTION AND MAINTENANCE TREATMENT FOR PATIENTS WITH MODERATELY TO SEVERELY ACTIVE CROHN’S DISEASE

A.3.1

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

A Phase III study to assess whether etrolizumab is a safe and effective treatment for patients with moderately to severely active Crohn's disease

A.4.1

Sponsor's protocol code number

GA29144

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	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.5.6	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/F04-02
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	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/F08-02
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	210
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.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 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

Crohn`s Disease

E.1.1.1

Medical condition in easily understood language

A form of inflammatory bowel disease

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011401
E.1.2	Term	Crohn's disease
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Efficacy Objectives
Induction Phase (IP)
• To independently evaluate the efficacy of etrolizumab dose regimens compared with placebo in inducing clinical remission and endoscopic improvement at the end of the Induction Phase (Week 14)

Maintenance Phase (MP)
• To independently evaluate the efficacy of etrolizumab compared with placebo in achieving clinical remission and endoscopic improvement at 1 year of maintenance treatment (Week 66), for patients who achieved a Crohn’s Disease Activity Index (CDAI) 70 response (defined as a decrease of at least 70 points from baseline CDAI) at Week 14

Safety Objectives
• To evaluate the overall safety and tolerability of etrolizumab compared with placebo during Induction and Maintenance Phases of therapy

E.2.2

Secondary objectives of the trial

Evaluate in IP the efficacy of etrolizumab compared with placebo:
•in achieving clinical remission at Week 6
•in achieving an SES-CD ≤4, with no segment having a subcategory score that is >1, at Week 14
• in achieving a reduction of CD signs and symptoms

Evaluate in MP the efficacy of etrolizumab compared with placebo:
•in maintaining clinical remission at Week 66 for patients who achieved clinical remission at Week 14
•in achieving corticosteroid-free clinical remission at Week 66
•in maintaining endoscopic improvement at Week 66 for patients who achieved endoscopic improvement at Week 14
•in achieving a SES CD ≤4, with no segment having a subcategory score that is >1, at Week 66
•in achieving durable clinical remission during 1 year of maintenance therapy
•in change of CD signs and symptoms from baseline to Week 66
•corticosteroid-free clinical remission at Week 66 in patients who were receiving corticosteroids at baseline

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

The main protocol contains all details of the sub-study. There are no separate documents (with title, date and version) for the substudy. The objective of the substudy is to determine the relationship between etrolizumab exposure and receptor occupancy in peripheral blood in patients with CD. To achieve this objective, it is planned to enroll approximately 150 patients in the substudy. Blood sampling for the PK/PD substudy will continue in the Maintenance Phase. Patients in all cohorts will provide blood samples for population PK analysis and PD characterization.

E.3

Principal inclusion criteria

- 18-80 years of age (inclusive)
- Moderately to severely active Crohn's disease as determined by the Crohn's Disease Activity Index (CDAI), patient reported outcomes and endoscopically defined disease activity in the ileum and/or colon
- Intolerance, loss of response or failure to respond to corticosteroids (CS) or, immunosuppressants (IS), or TNF inhibitors within the previous 5 years
- Use of effective contraception as defined by the protocol

E.4

Principal exclusion criteria

- A history of, or current conditions affecting the digestive tract, such as ulcerative colitis, indeterminant colitis, abdominal or perianal abscess, adenomatous colonic polyps, colonic mucosal dysplasia, and short bowel syndrome
- Sinus tract with evidence for infection (e.g., Fistula with purulent discharge) in the clinical judgment of the investigator. Fistulas related to Crohn’s disease are not exclusionary
- Planned surgery for CD
- Ileostomy or colostomy
- Has 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, active or latent tuberculosis (patients with prior history of BCG vaccination must pass protocol-defined screening criteria)

E.5 End points

E.5.1

Primary end point(s)

a, Induction Phase
•Clinical remission at Week 14
•Endoscopic improvement at Week 14

b, Maintenance Phase, among patients who achieve CDAI-70 response at Week 14
•Clinical remission at Week 66
•Endoscopic improvement at Week 66

E.5.1.1

Timepoint(s) of evaluation of this end point

a, at Week 14
b, at Week 66

E.5.2

Secondary end point(s)

Induction Phase
a, Clinical remission at Week 6
b, SES CD ≤4 (≤2 for ileal patients), with no segment having a subcategory score that is >1, at Week 14
c, Change in CD signs and symptoms from baseline to Week 14 as assessed by the CD-PRO/SS measure

Maintenance Phase
a, Clinical remission at Week 66 among patients who achieved clinical remission at Week 14
b, Corticosteroid-free clinical remission at Week 66 among patients who were receiving corticosteroids at baseline
c, Endoscopic improvement at Week 66 among patients who achieved endoscopic improvement at Week 14
d, SES CD ≤4 (≤2 for ileal patients), with no segment having a subcategory score that is >1, at Week 66
e, Durable clinical remission
f, Corticosteroid-free clinical remission for 24 weeks at Week 66 among patients who were receiving corticosteroids at baseline
g, Change in CD signs and symptoms from baseline to Week 66 as assessed by the CD-PRO/SS measure

E.5.2.1

Timepoint(s) of evaluation of this end point

Induction Phase
a, At Week 6
b, At Week 14
c, From baseline to Week 14

Maintenance Phase
a to d. at Week 66
e. Baseline, Week 24, 28, 32, 44, 56, and 66
f. Week 24 to Week 66
g. From baseline to Week 66

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

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

Exploratory biomarkers

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

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.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

200

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

Argentina

Australia

Brazil

Canada

Israel

Korea, Republic of

Mexico

New Zealand

Russian Federation

Serbia

South Africa

Turkey

Ukraine

United States

Austria

Belgium

Bulgaria

Croatia

Estonia

France

Germany

Hungary

Italy

Latvia

Lithuania

Netherlands

Poland

Romania

Slovakia

Spain

Sweden

Switzerland

United Kingdom

Czechia

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 meeting one of the following criteria, whichever is later:
-Completion of the 12-week Safety Follow-up Phase for the last patient in the Induction Phase
-The final visit for the last Induction patient transferred to Part 1 (OLE) of Study GA29145
-Completion of the 12-week Safety Follow-up Phase for the last patient in the Maintenance Phase
-The final visit for the last Maintenance patient transferred to Part 1 (OLE) of Study GA29145

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:

1100

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

565

F.4.2.2

In the whole clinical trial

1150

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 enrolled in this study may be eligible to participate in an open-label extension−safety monitoring (OLE-SM) study (GA29145), which consists of two parts: Part 1 (designated OLE [open-label extension]) and Part 2 (designated SM [safety monitoring]).
All of the inclusion and exclsion criteria for the OLE-SM study (GA29145) are listed in section 4.5.9 in the GA29144 protocol.

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

2015-05-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-09-07

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