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

• Register: EUCTR
• Last refreshed on: 21 March 2022
• Main ID: EUCTR2014-003824-36-SE
• Date of registration: 27/01/2015
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Phase III study to assess whether etrolizumab is a safe and effective treatment for patients with moderately to severely active Crohn's disease
• Scientific title: 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
• Date of first enrolment: 12/08/2015
• Target sample size: 1250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003824-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 8
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Czech Republic, Estonia, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Mexico, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

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

Are the trial subjects under 18? no
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 1200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

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)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Crohn`s Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Etrolizumab
Product Code: Ro 549-0261/F04-02
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Etrolizumab
CAS Number: 1044758-60-2
Current Sponsor code: RO5490261
Other descriptive name: ETROLIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 105-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: Etrolizumab
Product Code: Ro 549-0261/F08-02
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Etrolizumab
CAS Number: 1044758-60-2
Current Sponsor code: RO5490261
Other descriptive name: ETROLIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 210-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: a, at Week 14

b, at Week 66

Primary end point(s): a, Induction Phase
• Clinical remission at Week 14
• Endoscopic improvement at Week 14

b, Maintenance Phase
• Clinical remission at Week 66
• Endoscopic improvement at Week 66

Main Objective: 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
• To evaluate the efficacy of etrolizumab compared 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

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

Secondary Outcome(s)

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. From baseline to Week 66
f. At Week 66
g. From baseline to Week 66

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
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
g, Change in CD signs and symptoms from baseline to Week 66 as assessed by the CD-PRO/SS measure

Secondary ID(s)

GA29144

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 12/08/2015
Contact: