Phase 3
N=1,035
A Study to Assess Whether Etrolizumab is a Safe and Efficacious Treatment for Participants With Moderately to Severely Active Crohn's Disease
Crohn Disease
Bottom Line
View on ClinicalTrials.gov: NCT02394028 ↗Enrolled (actual)
1,035
Serious AEs
11.7%
Results posted
Nov 2022
Primary outcome: Primary: Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14 — 11.9; 20.00; 27.3 Percentage of Particiapnts
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Etrolizumab (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Sep 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 14 |
11.9; 20.00; 27.3 | — |
| PRIMARY Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 14 |
29.5; 29.3; 29.2; 30.1; 33.1 | 0.8508 |
| PRIMARY Induction Phase: Cohort 1: Percentage of Participants With Endoscopic Improvement at Week 14 |
3.4; 19.5; 16.8 | — |
| PRIMARY Induction Phase: Cohort 2 and 3: Percentage of Participants With Endoscopic Improvement at Week 14 |
20.8; 22.2; 21.6; 26.2; 27.4 | 0.7908 |
| PRIMARY Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66 |
24.00; 35.00 | 0.0088 sig |
| PRIMARY Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 |
12.2; 23.6 | 0.0026 sig |
| SECONDARY Induction Phase: Cohort 1: Percentage of Participants With Clinical Remission at Week 6 |
5.1; 15.0; 24.8 | — |
| SECONDARY Induction Phase: Cohort 2 and 3: Percentage of Participants With Clinical Remission at Week 6 |
20.5; 21.3; 20.8; 23.8; 23.4 | 1 |
| SECONDARY 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 |
1.7; 13.8; 8.3 | — |
| SECONDARY 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 |
9.9; 12.3; 8.7; 10.2; 15.3 | 1 |
| SECONDARY Induction Phase: Cohort 1: Change From Baseline in Crohn's Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 |
-0.7; -1.4; -1.6; -0.7; -1.5; -1.3 | 0.3110 |
| SECONDARY 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 |
-2.0; -2.3; -1.9; -1.6; -1.9; -2.3 | 1 |
| SECONDARY Maintenance Phase: Percentage of Participants With Clinical Remission at Week 66, Among Those Who Achieved Clinical Remission at Week 14 |
39.2; 56.5 | 0.0677 |
| SECONDARY Maintenance Phase: Percentage of Participants With Corticosteroid-Free Clinical Remission at Week 66, Among Those Who Were Receiving Corticosteroids at Baseline |
11.0; 29.0 | 0.0480 sig |
| SECONDARY Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 66 Among Participants Who Achieved Endoscopic Improvement at Week 14 |
25.3; 37.5 | 0.1210 |
| SECONDARY 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 |
5.9; 12.1 | 0.0480 sig |
| SECONDARY Maintenance Phase: Percentage of Participants With Durable Clinical Remission |
19.8; 30.9 | 0.0677 |
| SECONDARY 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 |
9.9; 25.8 | 0.0035 sig |
| SECONDARY Maintenance Phase: Change From Baseline in CD-PRO/SS Score at Week 66 |
-1.7; -2.0; -1.4; -1.7 | 0.4009 |
| SECONDARY 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) |
50; 83; 82; 120; 115; 51 | — |
| SECONDARY Overall Number of Participants With Adverse Events Leading to Study Drug Discontinuation |
2; 4; 1; 2; 5; 2 | — |
| SECONDARY Overall Number of Participants Who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 |
8; 10; 16; 38; 21; 8 | — |
| SECONDARY Overall Number of Participants Who Experienced at Least One Infection-Related Serious Adverse Event |
2; 4; 1; 2; 5; 1 | — |
| SECONDARY Overall Number of Participants Who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0 |
4; 7; 3; 10; 8; 1 | — |
| SECONDARY Overall Number of Participants Who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0 |
0; 0; 1; 2; 1; 0 | — |
| SECONDARY Overall Number of Participants Who Develop Malignancies |
0; 1; 1; 0; 1; 0 | — |
| SECONDARY Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab |
4.1; 2.8; 2.8; 5.6; 2.8; 0 | — |
| SECONDARY Observed Trough Serum Concentration (Ctrough) of Etrolizumab |
9.39; 25.1; 10.3; 25.7; 9.78; 25.5 | — |
Summary
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02394028). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.