A study of the effectiveness (efficacy) and safety of etrolizumab treatment, compared with Adalimumab and Placebo, in inducing disease remission in ulcerative colitis patients who have not previously received TNF inhibitors

• Register: EUCTR
• Last refreshed on: 21 September 2020
• Main ID: EUCTR2013-004277-27-LV
• Date of registration: 21/07/2014
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A study of the effectiveness (efficacy) and safety of etrolizumab treatment, compared with Adalimumab and Placebo, in inducing disease remission in ulcerative colitis patients who have not previously received TNF inhibitors
• Scientific title: PHASE III, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PLACEBOCONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY (INDUCTION OF REMISSION) AND SAFETY OF ETROLIZUMAB COMPARED WITH ADALIMUMAB AND PLACEBO IN PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS WHO ARE NAIVE TO TNF INHIBITORS - HIBISCUS II
• Date of first enrolment: 28/07/2014
• Target sample size: 350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004277-27
• 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: double-dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• 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, Brazil, Bulgaria, Colombia, Croatia, Czech Republic, Greece, Hungary, Latvia, Lithuania, Malaysia, New Zealand, Poland, Russian Federation, Turkey, 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 ulcerative colitis (UC) as determined by the Mayo Clinic Score assessment (MCS of 6-12)
- Naive to treatment with TNF inhibitor therapy
- An inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment
- Background regimen for UC may include oral 5-ASA, oral corticosteroids, budesonide therapy, probiotics, AZA, 6-MP, or MTX if doses have been stable during the screening period
- Use of highly effective contraception as defined by the protocol
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 rituximab
- Any treatment with tofacitinib during screening
- Any prior treatment with anti-adhesion molecules (e.g., anti-MAdCAM-1)
- Chronic hepatitis B or C infection, HIV or tuberculosis (active or latent)
- Neurological conditions or diseases that may interfere with monitoring
for PML
- History of demyelinating disease


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

Trade Name: Humira
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Current Sponsor code: RO5516922
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Humira
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Current Sponsor code: RO5516922
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Humira
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Current Sponsor code: RO5516922
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: • To evaluate the efficacy of etrolizumab compared with placebo for the induction of remission at Week 10

Secondary Objective: • To evaluate the efficacy of etrolizumab for the induction of remission
(compared with adalimumab only), clinical remission, clinical response, improvement in endoscopic appearance of the mucosa, endoscopic
remission and histologic remission at Wk 10
• To evaluate the efficacy of etrolizumab compared with placebo in achieving remission at Wk 10 and maintaining it to Wk 14
• To evaluate the efficacy of etrolizumab for onset of action, defined as
change from baseline in MCS rectal bleeding and stool frequency subscores at Wk 6
• To evaluate the efficacy of etrolizumab for UC bowel movement signs
and symptoms abdominal symptoms at Wk 10 as assessed by the UC
Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) measure
• To evaluate the efficacy of etrolizumab for patient-reported healthrelated
QOL at Wk 10 assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ)
• To evaluate the overall safety and tolerability of etrolizumab during
induction of remission of UC

Primary end point(s): Induction of remission compared with placebo as determined by the Mayo Clinic Score (MCS)

Timepoint(s) of evaluation of this end point: Week 10

Secondary Outcome(s)

Secondary end point(s): 1. Induction of remission compared with adalimumab as determined by the Mayo Clinic Score (MCS)at Week 10
2. Clinical remission at Week 10
3. Clinical response at Week 10
4. Improvement in endoscopic appearance of the mucosa at Week 10
5. Endoscopic remission at Week 10
6. Remission at Week 10 and Week 14
7. Histologic remission at Week 10
8. Change from baseline in MCS rectal bleeding subscore at Week 6
9. Change from baseline in MCS stool frequency subscore at Week 6
10. Change from baseline to Week 10 in UC bowel movement signs and
symptoms as assessed by the UC-PRO/SS
11. Change from baseline to Week 10 in UC abdominal symptoms as
assessed by the UC-PRO/SS
12. Change from baseline to Week 10 in patient's health-related QOL as
assessed by the overall score of the IBDQ
13. Incidence and severity of adverse events, infection related adverse
events, injection site reactions, adverse events leading to study drug
discontinuation, laboratory abnormalities, of hypersensitivity reaction
event
14. Incidence of anti-therapeutic antibodies (ATAs) to etrolizumab
15. Serum concentration during drug washout (through end of safety
follow up) etrolizumab
16. Serum concentration at primary and secondary endpoints Weeks 10
and 14

Timepoint(s) of evaluation of this end point: 1-5. Week 10
6. Week 10 and Week 14
7. Week 10
8-9. Baseline to Week 6
10-12. Baseline to Week 10
13. Up to 14 weeks
14-15. Week 0, Week 10, Week 14, unscheduled visit, early with drawn
from treatment phase and 12 weeks safety follow-up
16. At Week 10 and Week 14

Secondary ID(s)

NCT02171429

GA28949

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 25/07/2014
Contact: