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

• Register: EUCTR
• Last refreshed on: 28 September 2020
• Main ID: EUCTR2013-004282-14-DE
• Date of registration: 18/07/2014
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A study to evaluate the effectiveness (efficacy) and safety of etrolizumab compared with infliximab in patients with moderate to severe ulcerative colitis who have not previously received TNF inhibitors
• Scientific title: 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 - GARDENIA
• Date of first enrolment: 10/11/2014
• Target sample size: 390
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004282-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Double-dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Netherlands, Norway, Portugal, Romania, Singapore, South Africa, Spain, Sweden, Switzerland, United Kingdom

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.
- Diagnosis of UC established at least 3 months Prior to Day 1 by clinical and endoscopic evidence
- Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
- Evidence of UC extending a minimum of 20 cm from the anal verge as determined by baseline endoscopy
- Naive to treatment with any anti-TNF inhibitor therapy
- An inadequate response to, loss of response to, or intolerance to prior corticosteroid and/or immunosuppressant treatment
- Background regimen for UC may include oral 5-aminosalicylic acid (5-ASA), oral corticosteroids, budenoside, probiotics, azathioprine (AZA), 6-
mercaptopurine(6-MP), or methotrexate (MTX) if doses are stable, as defined by the protocol
- Use of highly effective contraception as defined by the protocol
- Received a colonoscopy within the past year or be willing to undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening
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 370
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
- Prior extensive colonic resection, subtotal or total colectomy, or planned surgery for UC
- A history of or current conditions and diseases affecting the digestive tract, such as ileostomy or colostomy 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
- Have received non-permitted inflammatory bowel disease (IBD) therapies (including etrolizumab or other anti-integrin agents such as natalizumab, vedolizumab, and efalizumab), as stated in the protocol
- Any prior treatment with anti-adhesion molecules (e.g., anti-MAdCAM-1)
- Any prior treatment with rituximab
- Any treatment with tofacitinib during screening
- History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies, fusion proteins,
or murine proteins or hypersensitivity to etrolizumab or any of the excipients
- Neurologic conditions or diseases that may interfere with monitoring for PML
- History of demyelinating disease
- Clinically significant abnormalities on screening neurologic examination (PML Objective/Subjective Checklists)
- History of cancer, including hematologic malignancy, solid tumors, and carcinoma in situ, within 5 years before screening, as defined by the
protocol
- Congenital or acquired immune deficiency, chronic hepatitis B or C infection, HIV positive or history of tuberculosis (active or latent)
- Evidence of or treatment for Clostridium difficile (as assessed by C. difficile toxin testing) within 60 days prior to Day 1 or other intestinal
pathogens within 30 days prior to Day 1.
- Evidence of or treatment for clinically significant cytomegalovirus (CMV) colitis within 60 days prior to Day 1.
- History of recurrent opportunistic infections and/or history of severe disseminated viral infections, or organ transplant
- Any serious opportunistic infection within the last 6 months
- Any major episode of infection requiring treatment with IV antibiotics within 8 weeks prior to screening or oral antibiotics within 4 weeks prior
to screening
- Received a live attenuated vaccine within 4 weeks prior to Day 1


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

Health Condition(s) or Problem(s) studied

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

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: Etrolizumab
Product Code: Ro 549-0261/F04
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

Trade Name: Remicade
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Current Sponsor code: RO6897845
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Both clinical response at W10 and clinical remission at W54 in patients with ulcerative colitis as determined by MCS

Main Objective: To evaluate the efficacy of etrolizumab compared with infliximab in achieving both clinical response at Week (W) 10, and clinical Remission at W54 in patients with ulcerative colitis as determined by the Mayo Clinic Score (MCS)

Secondary Objective: To evaluate:
• Clinical remission at W10, W54
• Clinical remission achieved at both W10 and W54
• Clinical remission at W54 among patients with a clinical response at W10
• Improvement in endoscopic appearance of the mucosa at W10, W54
• Improvement in endoscopic appearance of the mucosa achieved at both W10 and W54
• Endoscopic remission at W54
• Clinical response at W10
• Clinical response achieved at both W10 and W54
• Corticosteroid-free clinical remission at W54 (off corticosteroids for at least 24 weeks prior to W54) in patients who were receiving corticosteroids at baseline
• Change from baseline in patient-reported health-related QOL at W10, 30, and 54
• The overall safety and tolerability of etrolizumab over a period of 54 weeks
• Incidence and the clinical significance of anti-therapeutic antibodies to etrolizumab, or if necessary, infliximab
• Etrolizumab serum concentration at the time of primary endpoint evaluation and at a predose timepoint W12

Timepoint(s) of evaluation of this end point: W10 and 54

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) W10
2) W54
3) W10, and 54
4) W 54 among W10
5) W10
6) W54
7) W10, and 54
8) W54
9) W10
10) At W10, and 54
11) Baseline and W54
12) Baseline W10, 30, and 54
13-16) Baseline up to end of study (up to W66)
17, 18) W0 to W52
19) Baseline up to W54
20) Baseline up to end of study (up to W66)10) At baseline and Week 54
21) Baseline, W10 and W54
22) Baseline up to end of study (up to W66)
23) W2, W12 to W54
24) W10, 30 and 54.

Secondary end point(s): 1) Clinical remission at W10
2) Clinical remission at W54
3) Clinical remission achieved at both W10 and W54
4) Clinical remission at W54 among patients with a clinical response at W10
5) Improvement in endoscopic appearance of the mucosa at W10
6) Improvement in endoscopic appearance of the mucosa at W54
7) Improvement in endoscopic appearance of the mucosa achieved at both W10 and W54
8) Endoscopic remission at W54
9) Clinical response at W10
10) Clinical response achieved at both W10 and W54
11) Corticosteroid-free clinical remission at W54 in patients who were receiving corticosteroids at baseline
12) Change from baseline in patient-reported health-related QOL at W10, 30, and 54, as assessed by the Inflammatory Bowel Disease
Questionnaire
13) Incidence and severity of adverse events
14) Incidence of serious adverse events
15) Incidence and severity of infection-related adverse events
16) Incidence of serious infection-related adverse events
17) Incidence and severity of injection-site reactions
18) Incidence of adverse events leading to study drug discontinuation
19) Incidence of laboratory abnormalities
20) Incidence of malignancies
21) Incidence of Anti-Therapeutic Antibodies (ATAs) to etrolizumab, or if necessary, infliximab
22) Incidence and severity of hypersensitivity reaction events
23) Serum concentration 2 weeks after the first dose and at steady state during the dosing period from W12 to W54
24) Serum concentration at timepoints W10, 30, and 54

Secondary ID(s)

NCT02136069

GA29103

2013-004282-14-GB

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 10/11/2014
Contact: