A Study Comparing the Efficacy and Safety of Etrolizumab to Infliximab in Participants With Moderate to Severe Ulcerative Colitis Who Are Naïve to Tumor Necrosis Factor (TNF) Inhibitors (GARDENIA)

Roche

Status and phase: Completed; Phase 3

Conditions: Ulcerative Colitis

Treatments: Other: Placebo (Injection); Other: Placebo (IV); Drug: Infliximab; Drug: Etrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02136069

2013-004282-14 (EudraCT Number)

GA29103

Details and patient eligibility

About

This is a multicenter, Phase III, randomized, double-blind, double-dummy, parallel-group study to evaluate the safety, efficacy, and tolerability of etrolizumab compared with infliximab in treating participants with moderate to severe ulcerative colitis (UC) who are naive to tumor necrosis factor (TNF) inhibitors. Participants will be randomized in a 1:1 ratio to receive either etrolizumab 105 milligrams (mg) by subcutaneous (SC) injection once every 4 weeks (Q4W) + placebo (intravenous [IV] infusion at Weeks 0, 2, and 6, then once every 8 weeks [Q8W]) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then Q8W) + placebo (SC Q4W). Time on treatment is 54 weeks.

Enrollment: 397 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
• Naive to treatment with any anti-TNF inhibitor therapy (including TNF inhibitor biosimilars)
• An inadequate response to or intolerance of prior corticosteroid and/or immunosuppressant treatment
• Background regimen for UC may include oral 5-aminosalicylate (5-ASA), oral corticosteroids, budenoside multi-matrix system (MMX), probiotics, azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) if doses have been stable during the screening period
• Use of highly effective contraception during and at least 24 weeks after the last dose of study drug

Exclusion criteria

• A history of or current conditions and diseases affecting the digestive tract, such as indeterminate colitis, suspicion of ischemic, radiation 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, efalizumab, and tofactinib)
• History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies; fusion proteins, or murine proteins; hypersensitivity to etrolizumab or any of its excipients
• Chronic hepatitis B or C infection, Human deficiency virus (HIV) or tuberculosis (active or latent)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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397 participants in 2 patient groups

Etrolizumab + Placebo (IV)

Experimental group

Description:

Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.

Treatment:

Drug: Etrolizumab

Other: Placebo (IV)

Infliximab + Placebo (Injection)

Active Comparator group

Description:

Participants will receive IV infusion of infliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to etrolizumab by SC injection Q4W until Week 52.

Treatment:

Other: Placebo (Injection)

Drug: Infliximab