A Study of the Efficacy and Safety of Etrolizumab Treatment in Maintenance of Disease Remission in Ulcerative Colitis (UC) Participants Who Are Naive to Tumor Necrosis Factor (TNF) Inhibitors

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02165215
• Date of registration: 13/06/2014
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of the Efficacy and Safety of Etrolizumab Treatment in Maintenance of Disease Remission in Ulcerative Colitis (UC) Participants Who Are Naive to Tumor Necrosis Factor (TNF) Inhibitors LAUREL
• 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
• Date of first enrolment: August 12, 2014
• Target sample size: 359
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02165215
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Brazil, Canada, Czech Republic, Czechia, Denmark, Germany, Hungary, India, Israel, Italy, Mexico, Poland, Slovakia, South Africa, Ukraine, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of ulcerative colitis (UC) established at least 3 months prior to Day 1 by
clinical and endoscopic evidence

- Moderately to severely active UC as determined by an MCS of 6-12 with an endoscopic
subscore greater than or equal to (=)2 as determined by the central reading procedure
(endoscopy to be performed 4-16 days prior to Day 1), a rectal bleeding subscore =1,
and a stool frequency subscore =1 during the screening period (prior to Day 1)

- Evidence of UC extending a minimum of 20 centimeters (cm) from the anal verge as
determined by baseline endoscopy (flexible sigmoidoscopy or colonoscopy) performed
during screening, 4-16 days prior to Day 1

- Naive to treatment with any anti-TNF therapy

- Participants must have had an inadequate response, loss of response, or intolerance to
prior corticosteroid and/or immunosuppressant treatment

- Background regimen for UC may include oral 5-aminosalicylate (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

- Must have received a colonoscopy within the past year or be willing to undergo a
colonoscopy in lieu of a flexible sigmoidoscopy at screening

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

- Any prior treatment with etrolizumab or other anti-integrin agents (including
natalizumab, vedolizumab, and efalizumab) as stated in the protocol

- Any prior treatment with anti-adhesion molecules (such as mucosal addressin cell
adhesion molecule [MAdCAM-1])

- Any prior treatment with rituximab

- Any treatment with tofacitinib during screening

- Cogenital 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 and/or severe disseminated viral
infections

- History of 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: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Colitis, Ulcerative

Intervention(s)

Drug: Etrolizumab

Drug: Placebo

Primary Outcome(s)

Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants with a Clinical Response at Week 10, as Determined by the Mayo Clinic Score (MCS) [Time Frame: Week 62]

Secondary Outcome(s)

Maintenance Phase: Percentage of Participants with Corticosteroid-Free Remission at Week 62 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [Time Frame: Baseline, Week 62]

Induction Phase: Change from Baseline to Week 6 in MCS Stool Frequency Subscore [Time Frame: Baseline, Week 6]

Maintenance Phase: Change from Baseline to Week 62 in UC Abdominal Symptoms, as Assessed by the UC-PRO/SS Questionnaire [Time Frame: Baseline, Week 62]

Number of Participants with Malignancies [Time Frame: From Baseline up to Week 74]

Maintenance Phase: Change from Baseline to Week 62 in UC Bowel Movement Signs and Symptoms, as Assessed by the Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Questionnaire [Time Frame: Baseline, Week 62]

Etrolizumab Serum Trough Concentration [Time Frame: Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62]

Maintenance Phase: Change from Baseline to Week 62 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ) [Time Frame: Baseline, Week 62]

Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission at Week 62 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [Time Frame: Baseline, Week 62]

Maintenance Phase: Percentage of Participants with Endoscopic Remission at Week 62, as Determined by the MCS Endoscopic Subscore [Time Frame: Week 62]

Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Etrolizumab [Time Frame: Baseline, Weeks 4, 12, 24, 44, and 62, and and Early Termination/End of Safety Follow-Up (up to Week 74)]

Number of Participants with at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v4.0) [Time Frame: From Baseline up to Week 74]

Induction Phase: Change from Baseline to Week 6 in MCS Rectal Bleed Subscore [Time Frame: Baseline, Week 6]

Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants in Remission at Week 10, as Determined by the MCS [Time Frame: Week 62]

Maintenance Phase: Percentage of Participants Who Maintained Clinical Remission at Week 62 Among Randomized Participants in Clinical Remission at Week 10, as Determined by the MCS [Time Frame: Week 62]

Maintenance Phase: Percentage of Participants with Improvement from Baseline in Endoscopic Appearance of the Mucosa at Week 62, as Determined by the MCS Endoscopic Subscore [Time Frame: Baseline, Week 62]

Number of Participants with Adverse Events Leading to Study Drug Discontinuation [Time Frame: From Baseline up to Week 74]

Number of Participants with Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0 [Time Frame: From Baseline up to Week 74]

Number of Participants with Injection-Site Reactions by Severity, According to NCI-CTCAE v4.0 [Time Frame: From Baseline up to Week 74]

Number of Participants with Serious Infection-Related Adverse Events [Time Frame: From Baseline up to Week 74]

Maintenance Phase: Percentage of Participants in Clinical Remission at Week 62, as Determined by the MCS [Time Frame: Week 62]

Maintenance Phase: Percentage of Participants with Histologic Remission at Week 62, as Determined by the Nancy Histological Index [Time Frame: Week 62]

Number of Participants with Hypersensitivity Reaction Events by Severity, According to NCI-CTCAE v4.0 [Time Frame: From Baseline up to Week 74]

Secondary ID(s)

GA29102

2013-004280-31

Source(s) of Monetary Support

Please refer to primary and secondary sponsors