A study to investigate the effectiveness (efficacy) and safety of etrolizumab in ulcerative colitis patients who have been previously exposed to TNF inhibitors.

• Register: EUCTR
• Last refreshed on: 1 October 2018
• Main ID: EUCTR2013-004278-88-HU
• Date of registration: 10/06/2014
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A study to investigate the effectiveness (efficacy) and safety of etrolizumab in ulcerative colitis patients who have been previously exposed to TNF inhibitors.
• Scientific title: PHASE III, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE EFFICACY AND SAFETY OF ETROLIZUMAB DURING INDUCTION AND MAINTENANCE IN PATIENTS WITH MODERATE TO SEVERE ACTIVE ULCERATIVE COLITIS WHO HAVE BEEN PREVIOUSLY EXPOSED TO TNF INHIBITORS - HICKORY
• Date of first enrolment: 04/08/2014
• Target sample size: 605
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004278-88
• 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: Cohort 1 (open label) and Cohort 2 (blinded); If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Lithuania, Mexico, Netherlands, Poland, Romania, Spain, Switzerland, United Kingdom, 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:
- Treatment within 5 years prior to screening with one or two induction regimens that contain TNF inhibitors (including TNF inhibitor biosimilars)
- 18-80 years of age, inclusive
- Diagnosis of UC established at least 3 months prior to Day 1
- Moderately to severely active UC as determined by the MCS
- Washout of TNF inhibitor therapy for at least 8 weeks preceding Day 1
- 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
- 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 575
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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 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: rhuMAb Beta7, Anti Beta7, PRO145223
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: • Clinical remission at W14 and W66
• Clinical response at W14
• Improvement in endoscopic appearance of the mucosa at W14 and W66
• Endoscopic and histologic remission at W14 and W66
• Change from baseline (BL) in rectal bleed and stool frequency subscore at W6
• Change from BL in UC bowel movement signs and symptoms and abdominal symptoms at W14 and W66, as assessed by Ulcerative Colitis Patient Reported Outcome Signs and Symptoms (UC-PRO/SS)
• Change from BL in Patient Reported health related Quality of Life at W14 and W66, as assessed by Inflammatory Bowel Disease Questionnaire (IBDQ)
• Clinical remission at W66 in patients in clinical remission at W14
• Remission at W66 among patients in remission at W14
• Corticosteroid (CS)-free clinical remission and remission at W66 in patients receiving CSs at BL
• Etrolizumab Serum Concentration
• Percentage of participants with Adverse Events
• Percentage of participants with Anti-Therapeutic Antibodies to Etrolizumab

Timepoint(s) of evaluation of this end point: 1) at week 14
2) at week 66

Main Objective: • To evaluate the efficacy of etrolizumab (105 mg subcutaneous [SC] every 4 weeks [Q4W]) compared with placebo for the induction of remission as determined by the Mayo Clinic Score (MCS) at Week (W) 14.
• To evaluate the efficacy of etrolizumab (105 mg SC Q4W) compared with placebo for remission at W66 among patients with a clinical response at W14, as determined by the MCS

Primary end point(s): 1) Remission at W 14, as determined by the Mayo Clinic Score (MCS)
2) Remission at W 66 among patients with a clinical response at W 14 as determined by MCS

Secondary Outcome(s)

Secondary end point(s): Percentage of participants in/with
1. Clinical remission at W14 and W66, as determined by MCS
2. Clinical response at W14, as determined by MCS
3. Improvement in endoscopic appearance of the mucosa at W14 and W66, as determined by Mayo Endoscopic Subscore
4. Endoscopic and histologic remission at W14 and W66, as determined by Mayo Endoscopic Subscore and Nancy Histological Index (NHI) respectively
5. Change from baseline in rectal bleed and stool frequency subscore at W6, as determined by Mayo rectal bleeding and stool frequency Subscores respectively
6. Change from baseline in UC bowel movement signs and symptoms and abdominal symptoms at W14 and W66, as assessed by UC-PRO/SS
7. Change from baseline in health-related Quality of Life at W14 and W66, as assessed by IBDQ
8. Clinical remission at W66 among patients in clinical remission at W14, as determined by MCS
9. Remission at W66 among patients in remission at W14, as determined by MCS
10. Corticosteroid (CS)- free clinical remission and remission at W66 in patients who were receiving CSs at baseline, as determined by MCS
11. Etrolizumab Serum Concentration
12. Adverse Events
13. Anti-Therapeutic Antibodies to Etrolizumab

Timepoint(s) of evaluation of this end point: 1. W14, W66
2. W14
3-4. W14, W66
5. Baseline (Day-35- Day-1), W6
6-7. Baseline, W14, W66
8-9. W14 and W66
10. W66
11. Pre-dose (0 hour) on Day 1, Post-dose W14, W24, W44, W66, early termination/end of safety follow-up (up to W78)
12. Baseline up to end of study (up to W78)
13. Pre-dose (0 hour) on Day 1, Post-dose W4, W14, W24, W44, W66, early termination/end of safety follow-up (up to W78)

Secondary ID(s)

GA28950

2013-004278-88-LT

NCT02100696

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd