A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors (HICKORY)

Roche

Status and phase: Completed; Phase 3

Conditions: Ulcerative Colitis

Treatments: Drug: Placebo; Drug: Etrozulimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02100696

2013-004278-88 (EudraCT Number)

GA28950

Details and patient eligibility

About

This Phase III, double-blind, placebo-controlled, multicenter study will investigate the efficacy and safety of etrolizumab during induction and maintenance of remission compared with placebo in the treatment of participants with moderately to severely active ulcerative colitis (UC) who have been previously exposed to TNF inhibitors.

Enrollment: 609 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of UC established at least 3 months prior to Day 1
• Moderately to severely active UC as determined by the Mayo Clinic Score (MCS) assessment
• Treatment within 5 years prior to screening with one or two induction regimens that contain TNF inhibitors (including TNF inhibitor biosimilars)
• Washout of anti-TNF 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
• Must 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

• 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
• Any prior treatment with etrolizumab or other anti-integrin agents (including natalizumab, vedolizumab, and efalizumab)
• Any prior treatment with anti-adhesion molecules (e.g. anti-MAdCAM-1)
• Any prior treatment with rituximab
• 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 or clinically significant cytomegalovirus (CMV) colitis within 60 days prior to Day 1
• Evidence of or treatment for other intestinal pathogens within 30 days prior to Day 1
• History of recurrent opportunistic infections and/or severe disseminated viral infections
• History of 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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609 participants in 6 patient groups, including a placebo group

Cohort 1: Etrolizumab (Open-Label Induction (OLI) Phase)

Experimental group

Description:

Participants assigned to this arm will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) for 14 weeks during the induction phase.

Treatment:

Drug: Etrozulimab

Cohort 2: Placebo (Double-Blind Induction Phase)

Placebo Comparator group

Description:

Participants randomized to this arm will receive treatment with double-blind placebo SC injection Q4W for 14 weeks during the induction phase.

Treatment:

Drug: Placebo

Cohort 2: Etrolizumab (Double-Blind Induction Phase)

Experimental group

Description:

Participants randomized to this arm will receive treatment with double-blind etrolizumab 105 mg SC injection Q4W for 14 weeks during the induction phase.

Treatment:

Drug: Etrozulimab

Placebo Responders: Placebo (Maintenance Phase)

Placebo Comparator group

Description:

Participants who received placebo during the induction phase, Cohort 2: Placebo (Double-Blind Induction Phase), and achieve a clinical response with placebo at Week 14 will continue to receive blinded placebo from Week 16 up to Week 66 during the maintenance phase.

Treatment:

Drug: Placebo

Etrolizumab Responders: Placebo (Maintenance Phase)

Placebo Comparator group

Description:

Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive placebo SC injection Q4W from Week 16 up to Week 66.

Treatment:

Drug: Placebo

Etrolizumab Responders: Etrolizumab (Maintenance Phase)

Experimental group

Description:

Participants who received etrolizumab during the induction phase, Cohort 1: Etrolizumab (Open-Label Induction Phase) and Cohort 2: Etrolizumab (Double-Blind Induction Phase), and achieved a clinical response at Week 14 will be re-randomized by Week 16 for the double-blind maintenance phase. Clinical responders re-randomized to this arm will receive etrolizumab 105 mg SC injection Q4W from Week 16 up to Week 66.

Treatment:

Drug: Etrozulimab