A study to investigate the effectiveness (efficacy) and safety of etrolizumab treatment in maintaining disease remission in ulcerative colitis patients who have not previously been treated with TNF inhibitors

• Register: EUCTR
• Last refreshed on: 19 April 2021
• Main ID: EUCTR2013-004280-31-DE
• Date of registration: 30/07/2014
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A study to investigate the effectiveness (efficacy) and safety of etrolizumab treatment in maintaining disease remission in ulcerative colitis patients who have not previously been treated with TNF inhibitors
• Scientific title: PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY (MAINTENANCE OF REMISSION) AND SAFETY OF ETROLIZUMAB COMPARED WITH PLACEBO IN PATIENTS WITH MODERATE TO SEVERE ACTIVE ULCERATIVE COLITIS WHO ARE NAIVE TO TNF INHIBITORS - LAUREL
• Date of first enrolment: 24/11/2014
• Target sample size: 350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004280-31
• 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: 10 wks open label induction treatment; 52 wks double-blind maintenance treatment; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; 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

Brazil, Canada, Czech Republic, Denmark, Germany, Hungary, Israel, Italy, Mexico, Poland, Slovakia, South Africa, Ukraine, 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.
- 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 therapy
-Patients must have an inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment
- Background regimen for UC may include oral 5-aminosalicylic acid (5-ASA), oral corticosteroids, budesonide, probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
- Use of highly effective contraception as defined by the protocol
- Must have 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 339
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

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.
- Any prior treatment with anti-adhesion molecules (e.g., anti-MAdCAM-1)
- Any prior treatment with rituximab
- Any treatment with tofacitinib during screening
- Congenital or acquired immune deficiency, chronic hepatitis B or C infection, Human Immunodeficiency Virus (HIV) positive, or history of tuberculosis (active or latent)
- Evidence of or treatment for Clostridium difficile within 60 days prior to Day 1 or other intestinal pathogens within 30 days prior to Day 1
- History of recurrent opportunistic infections, severe disseminated viral infections and organ transplant
- Any major episode of infection requiring treatment with intravenous (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 (UC)
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

Primary Outcome(s)

Secondary Objective: To evaluate
• Maintenance of clinical remission and remission at W 62 for patients in clinical remission and remission at W 10
• Clinical remission at W 62
• Remission at W62 among patients in remission at W10
• Improvement in endoscopic appearance of the mucosa at W 62
• Endoscopic remission at W 62
• Histologic remission at W 62
• Onset of action, defined as change from baseline in rectal bleed and stool frequency subscore at W 6
• Corticosteroid free clinical remission and remission at W 62 in patients who were receiving corticosteroids at baseline
• Change from baseline to W 62 in UC bowel movement signs and abdominal symptoms, as assessed by UC Patient-Reported Outcome
(PRO) Signs and Symptoms measure
• Change from baseline to W 62 in patient-reported health-related quality of life (QOL), as assessed by Inflammatory Bowel Disease
Questionnaire (IBDQ) score
• Etrolizumab serum concentration
• Overall safety and tolerability of etrolizumab over a period of 62 weeks

Main Objective: • To evaluate the efficacy of etrolizumab compared with placebo for remission at Week (W) 62 among patients with a clinical response at W10

Primary end point(s): Remission at W 62 among patients with a clinical response at W 10 as determined by MCS and concomitant treatment

Timepoint(s) of evaluation of this end point: Week 62

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-6) W 62
7-8) Baseline (Day 1) to W 6
9) W 62
10-12) Baseline to W 62
13-19) Up to W 62
20).W 0, W 4, W 12, W 24, W 44, W 62, unscheduled visit and at early withdrawal from treatment visit
21) From W 12 to W 62
22) At W 62

Secondary end point(s): 1) Proportion of patients in clinical remission at W 62 among patients in clinical remission at W 10
2) Proportion of patients in clinical remission at W 62
3) Proportion of patients in remission at W 62 among patients in remission at W 10
4) Proportion of patients with Improvement in endoscopic appearance of the mucosa at W 62
5) Proportion of patients in Endoscopic remission at W 62
6) Proportion of patients in Histologic remission at W 62
7) Change from baseline in rectal bleed subscore at W 6
8) Change from baseline in stool frequency subscore at W 6
9) Proportion of patients in Corticosteroid free clinical remission at W 62 in patients who are receiving corticosteroids at baseline
10) Change from baseline to W 62 in UC bowel movement signs and symptoms as assessed by the UC PRO/SS measure
11) Change from baseline to W 62 in UC abdominal symptoms as assessed by the UC PRO/SS measure
12) Change from baseline to W 62 in patients' health related QOL as assessed by the overall score of the IBDQ score
13) Incidence and severity of adverse events and serious adverse events
14) Incidence and severity of infection and serious infection-related adverse events
15) Incidence and severity of injection site reactions
16) Incidence of adverse events leading to study drug discontinuation
17) Incidence and severity of hypersensitivity reaction events
18) Incidence of laboratory abnormalities
19) Incidence of malignancies
20) Incidence of ATAs to etrolizumab
21) Serum trough concentration at steady state during the dosing period from W 12 to W 62
22) Serum concentration at primary endpoint time (W 62)

Secondary ID(s)

NCT02165215

2013-004280-31-CZ

GA29102

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 24/11/2014
Contact:

Results

• Results available: Yes
• Date Posted: 15/04/2021
• Date Completed: 06/04/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004280-31/results