A Study to Assess Whether Etrolizumab is a Safe and Efficacious Treatment for Participants With Moderately to Severely Active Crohn's Disease

Hoffmann-La Roche1,035 enrolled

Overview

This is a multicenter, Phase 3, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of etrolizumab compared with placebo during induction and maintenance treatment of moderately to severely active Crohn's Disease (CD). The target population includes participants with CD who are refractory or intolerant to corticosteroids (CS) and/or immunosuppressant (IS) therapy and who have either not received prior anti-tumor necrosis factor (anti-TNF) therapy (TNF-naive) or who have had prior exposure to anti-TNF therapies and demonstrated inadequate responses or intolerance to anti-TNFs. The study period will consist of a Screening Phase (up to 35 days) plus (+) a 14-week Induction Phase + a 52-week Maintenance Phase + a 12-week Safety Follow-up Phase. At Week 14 (end of Induction Phase), participants achieving a decrease from baseline of at least 70 points in the Crohn's Disease Activity Index (CDAI) score (CDAI-70 response) without the use of rescue therapy will continue to the Maintenance Phase.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

1,035

Conditions

Crohn Disease

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Moderately to severely active Crohn's Disease (CD) as determined by the CDAI, patient reported outcomes and endoscopically defined disease activity in the ileum and/or colon * Intolerance, refractory disease, or no response to corticosteroids (CS), immunosuppressants (IS), or anti-TNF therapy within 5 years from screening. Participants who have not previously demonstrated inadequate response or intolerance to one or more anti-TNF therapies are eligible to participate in the study provided they are intolerant or refractory to CS or IS therapy * Use of effective contraception as defined by the protocol Exclusion Criteria: * A history of, or current conditions affecting the digestive tract, such as ulcerative colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess, adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel syndrome * 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) * Any prior treatment with ustekinumab within 14 weeks prior to randomization * Chronic hepatitis B or C infection, human immunodeficiency virus (HIV), active or latent tuberculosis (participants with prior history of Bacillus Calmette-Guérin \[BCG\] vaccination must pass protocol-defined screening criteria) * Sinus tract with evidence for infection (e.g., purulent discharge) in the clinical judgment of the investigator. Fistulas related to CD are not exclusionary * Any prior treatment with anti-adhesion molecules (e.g., anti-mucosal addressin cell adhesion molecule \[anti-MAdCAM-1\]) * Any major episode of infection requiring treatment with intravenous antibiotics ≤8 weeks prior to screening or oral antibiotics ≤4 weeks prior to screening. Treatment with antibiotics as adjunctive therapy for CD in the absence of documented infection is not exclusionary * Hospitalization (other than for elective reasons) within 4 weeks prior to randomization

Locations (327)

Valley Gastroenterology Consultants

Arcadia, California, United States

University of California San Diego Medical Center

La Jolla, California, United States

VA Long Beach Healthcare System

Long Beach, California, United States

Digestive Care Associates, A Medical Corporation

San Carlos, California, United States

SDG Clinical Research

San Diego, California, United States

Outcomes

Primary Outcomes

Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14

Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.

Time frame: Week 14

Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14

Time frame: Week 14

Induction Phase: Cohort 1: Percentage of Participants With Endoscopic Improvement at Week 14

Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.

Time frame: Week 14

Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14

Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn's Disease (SES-CD) score.

Time frame: Week 14

Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66

Time frame: Baseline and Week 66

Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66

Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. Maintenance phase participants were evaluated.

Time frame: Week 66

Secondary Outcomes

Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 6

Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.

Time frame: Week 6

Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6

Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit.

Time frame: Week 6

Induction Phase: Cohort 1: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14

Endoscopic Remission is defined as SES-CD total score \<=4 (\<=2 for ileal only patients), with no segment having a subcategory score \>1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity.

Time frame: Week 14

Induction Phase: Cohort 2 and 3: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score Greater Than (>)1, at Week 14

Time frame: Week 14

Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14

CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available.

Induction Phase: Cohort 2 and 3: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14

Time frame: Baseline and Week 14

Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, Among Those Who Achieved Clinical Remission at Week 14

Time frame: Baseline, Weeks 14 and 66

Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline

Time frame: Baseline and Week 66

Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 Among Participants Who Achieved Endoscopic Improvement at Week 14

Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. Induction Phase Cohorts are not included

Time frame: Baseline, Weeks 14 and 66

Maintenance Phase: Percentage of Participants With SES-CD Score ≤4 (≤2 for Ileal Participants), With No Segment Having a Subcategory Score >1, at Week 66

Time frame: Week 66

Maintenance Phase: Percentage of Participants With Durable Clinical Remission

Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Durable clinical remission was defined as clinical remission at ≥4 of the 6 in-clinic assessment visits conducted during the Maintenance Phase at Weeks 24, 28, 32, 44, 56, and 66. Induction Phase Cohorts are not included

Time frame: Week 14 up to Week 66 (assessed at Weeks 24, 28, 32, 44, 56, and 66)

Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline

Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Percentage of participants with clinical remission who will be off corticosteroids for at least 24 weeks prior to Week 66 will be reported. Induction Phase Cohorts are not included

Time frame: Baseline and from Week 14 up to Week 66

Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66

Time frame: Baseline and Week 66

Overall Number of Participants Who Experienced 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)

Investigator text for AEs is coded using MedDRA version 24.0. For participants counts, multiple occurrences of AEs in the same category for an individual are counted only once. For event counts, multiple occurrences of AEs in the same category for an individual are counted separately. Severity Grades from 1 to 5.