A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors

• Register: ClinicalTrials.gov
• Last refreshed on: 2 August 2021
• Main ID: NCT02171429
• Date of registration: 20/06/2014
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors HIBISCUS II
• Scientific title: Phase III, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, 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
• Date of first enrolment: November 14, 2014
• Target sample size: 358
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02171429
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, Colombia, Croatia, Czechia, France, Greece, Hungary, Latvia, Lithuania, Malaysia, New Zealand, Poland, Russian Federation, Turkey, 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
randomization (Day 1)

- Moderately to severely active UC as determined by the MCS

- Naive to treatment with TNF inhibitor therapy

- An inadequate response, loss of response, or intolerance to prior corticosteroid
and/or immunosuppressant treatment

- Background UC therapy may include oral 5-aminosalisylate (5-ASA), budesonide, oral
corticosteroids, probiotics, azathioprine (AZA), 6-mercaptopurine (6MP), or
methotrexate (MTX) if doses have been stable for:

- AZA, 6-MP, MTX: 8 weeks immediately prior to randomization

- 5-ASA: 4 weeks immediately prior to randomization

- Corticosteroids: 4 weeks immediately prior to randomization; if corticosteroids are
being tapered, dose has to be stable for at least 2 weeks prior to randomization

- Use of highly effective contraception method 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

Exclusion Criteria:

Exclusion Criteria Related to Inflammatory Bowel Disease:

- Prior extensive colonic resection, subtotal or total colectomy, or planned surgery for
UC

- Past or present ileostomy or colostomy

- Diagnosis of indeterminate colitis

- Suspicion of ischemic colitis, radiation colitis, or microscopic colitis

- Diagnosis of toxic megacolon within 12 months of initial screening visit

- Any diagnosis of Crohn's disease

- Past or present fistula or abdominal abscess

- A history or current evidence of colonic mucosal dysplasia

- Patients with any stricture (stenosis) of the colon

- Patients with history or evidence of adenomatous colonic polyps that have not been
removed

Exclusion Criteria Related to Prior or Concomitant Therapy:

- Prior treatment with TNF-alpha antagonists

- Any prior treatment with etrolizumab or other anti-integrin agents

- Any prior treatment with rituximab

- Any treatment with tofacitinib during screening

- Any prior treatment with anti-adhesion molecules

- Use of intravenous (IV) steroids within 30 days prior to screening with the exception
of a single administration of IV steroid

- Use of agents that deplete B or T cells

- Use of anakinra, abatacept, cyclosporine, sirolimus, or mycophenolate mofetil (MMF)
within 4 weeks prior to randomization

- Chronic nonsteroidal anti-inflammatory drug (NSAID) use

- Patients who are currently using anticoagulants including, but not limited to,
warfarin, heparin, enoxaparin, dabigatran, apixaban, rivaroxaban

- Patients who have received treatment with corticosteroid enemas/suppositories and/or
topical (rectal) 5-ASA preparations within 2 weeks prior to randomization

- Apheresis (i.e., Adacolumn apheresis) within 2 weeks prior to randomization

- Received any investigational treatment including investigational vaccines within 5
half lives of the investigational product or 28 days after the last dose, whichever is
greater, prior to randomization

- History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to
chimeric, human, or humanized antibodies, fusion proteins, or murine proteins or
hypersensitivity to etrolizumab (active drug substance) or any of the excipients (L
histidine, L-arginine, succinic acid, polysorbate 20)

- Patients administered tube feeding, defined formula diets, or parenteral
alimentation/nutrition who have not discontinued these treatments within 3 weeks prior
to randomization

Exclusion Criteria Related to General Safety:

- Pregnant or lactating

- Lack of peripheral venous access

- Hospitalization (other than for elective reasons) during the screening period

- Significant uncontrolled comorbidity, such as cardiac (e.g., moderate to severe heart
failure New York Heart Association Class III/IV), pulmonary, renal, hepatic,
endocrine, or gastrointestinal disorders

- Neurological conditions or diseases that may interfere with monitoring for PML

- History of demyelinating disease

- Clinically significant abnormalities on screening neurologic examination (PML
Objective Checklist)

- Clinically significant abnormalities on the screening PML Subjective Checklist

- History of alcohol, drug, or chemical abuse less than 6 months prior to screening

- Conditions other than UC that could require treatment with >10 mg/day of prednisone
(or equivalent) during the course of the study

- History of cancer, including hematologic malignancy, solid tumors, and carcinoma in
situ, within 5 years before screening

Exclusion Criteria Related to Infection Risk

- Congenital or acquired immune deficiency

- Patients must undergo screening for HIV and test positive for preliminary and
confirmatory tests

- Positive hepatitis C virus (HCV) antibody test result

- Positive hepatitis B virus (HBV) antibody test result

- Evidence of or treatment for Clostridium difficile (as assessed by C. difficile toxin
testing) within 60 days prior to randomization or other intestinal pathogens (as
assessed by stool culture and ova and parasite evaluation) within 30 days prior to
randomization

- Evidence of or treatment for clinically significant cytomegalovirus (CMV) colitis
(based on the investigator's judgment) within 60 days prior to randomization

- History of active or latent TB

- History of recurrent opportunistic infections and/or history of severe disseminated
viral infections

- Any serious opportunistic infection within the last 6 months prior to screening

- Any current or recent signs or symptoms (within 4 weeks before screening and during
screening) of infection

- Any major episode of infection requiring treatment with 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 randomization

- History of organ transplant

Exclusion Criteria Related to Laboratory Abnormalities (at Screening)

- Serum creatinine >2 x upper limit of normal (ULN)

- ALT or AST >3 x ULN or alkaline phosphatase >3 x ULN or total bilirubin >2.5 x ULN

- Platelet count <100,000/uL

- Hemoglobin <8 g/dL


Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

Intervention(s)

Drug: Etrolizumab

Other: Etrolizumab Placebo

Drug: Adalimumab

Other: Adalimumab Placebo

Primary Outcome(s)

Percentage of Participants in Remission at Week 10 With Etrolizumab Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28949 Population [Time Frame: Week 10]

Secondary Outcome(s)

Change From Baseline in Health-Related Quality of Life at Week 10, as Assessed by the Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score, GA28949 Population [Time Frame: Baseline, Week 10]

Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population [Time Frame: Baseline, Week 10]

Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28949 Population [Time Frame: Week 10]

Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28949 Population [Time Frame: Week 10]

Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population [Time Frame: Pre-dose (0 hour) on Day 1 and Week 4, Week 10, Week 14, and early termination/end of safety follow-up (up to 26 weeks)]

Percentage of Participants in Endoscopic Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS Endoscopy Subscore, GA28948 & GA28949 Pooled Population [Time Frame: Week 10]

Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population [Time Frame: Week 10]

Change From Baseline in Ulcerative Colitis Bowel Movement Signs and Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population [Time Frame: Baseline, Week 10]

Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28949 Population [Time Frame: Baseline, Week 6]

Change From Baseline in Ulcerative Colitis (UC) Bowel Movement Signs and Symptoms at Week 10, as Assessed by the UC Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS), GA28949 Population [Time Frame: Baseline, Week 10]

Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS Endoscopy Subscore, GA28948 & GA28949 Pooled Population [Time Frame: Week 10]

Percentage of Participants With Histologic Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the Nancy Histological Index, GA28948 & GA28949 Pooled Population [Time Frame: Week 10]

Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population [Time Frame: Baseline, Week 6]

Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28949 Population [Time Frame: Baseline, Week 10]

Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population [Time Frame: From Baseline up to Week 10]

Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28949 Population [Time Frame: Week 10]

Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population [Time Frame: From Baseline until the end of study (up to 26 weeks)]

Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28949 Population [Time Frame: Weeks 10 and 14]

Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the Mayo Endoscopy Subscore, GA28949 Population [Time Frame: Week 10]

Change From Baseline in the MCS Stool Frequency Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population [Time Frame: Baseline, Week 6]

Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28949 Population [Time Frame: Baseline, Week 6]

Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population [Time Frame: From Baseline up to Week 10]

Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population [Time Frame: Week 10]

Percentage of Participants in Remission at Week 10 With Etrolizumab Compared With Adalimumab, as Determined by the MCS, GA28949 Population [Time Frame: Week 10]

Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28949 Population [Time Frame: Week 10]

Pharmacokinetics of Etrolizumab: Serum Concentration, GA28949 Population [Time Frame: Weeks 10 and 14]

Secondary ID(s)

GA28949

2013-004277-27

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/03/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02171429