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 - Full Text View

Purpose

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) by subcutaneous (SC) injection [SC] every 4 weeks [Q4W]) + placebo (intravenous [IV] infusion at Weeks 0, 2, and 6, then every 8 weeks) or infliximab 5 milligrams/kilogram (mg/kg) IV at Weeks 0, 2, and 6, then every 8 weeks) + placebo (SC Q4W). Time on treatment is 54 weeks.

Condition	Intervention	Phase
Ulcerative Colitis	Drug: etrolizumab Drug: infliximab Other: placebo (IV) Other: placebo (injection)	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
Official Title:	PHASE III, RANDOMIZED, MULTICENTER DOUBLE-BLIND, DOUBLE DUMMY STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ETROLIZUMAB COMPARED WITH INFLIXIMAB IN PATIENTS WITH MODERATE TO SEVERE ACTIVE ULCERATIVE COLITIS WHO ARE NAÏVE TO TNF INHIBITORS

Resource links provided by NLM:

Genetics Home Reference related topics: ulcerative colitis

MedlinePlus related topics: Ulcerative Colitis

Drug Information available for: Infliximab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Outcome Measure: Percentage of Participants in sustained remission determined by Mayo Clinic Score (MCS). Sustained remission is defined as MCS </=2 with individual sub scores </=1, a rectal bleeding sub score of 0 sustained at each of the Week 10 [ Time Frame: Week 10 ]
Percentage of Participants With sustained remission determined by Mayo Clinic Score (MCS). Sustained remission is defined as MCS </=2 with individual sub scores </=1, a rectal bleeding sub score of 0 sustained at Week 10 [ Time Frame: Week 30 ]
Percentage of Participants With sustained remission determined by Mayo Clinic Score (MCS). Sustained remission is defined as MCS </=2 with individual sub scores </=1, a rectal bleeding sub score of 0 sustained at Week 54 [ Time Frame: Week 30 ]

Secondary Outcome Measures:

Percentage of participants achieving clinical remission, defined as MCS </=2 with individual sub scores </=1 and a rectal bleeding sub score of 0 [ Time Frame: Week 54 ]
Percentage of participants achieving remission, defined as MCS </=2 with individual sub scores </=1 and a rectal bleeding sub score of 0 [ Time Frame: Week 10 and Week 54 ]
Percentage of participants achieving clinical response, defined as MCS with >/=3-point decrease and 30% reduction from baseline as well as >/=1-point decrease in rectal bleeding sub score or an absolute rectal bleeding score of 0 or 1 [ Time Frame: Weeks 10 ]
Percentage of participants that achieve remission corticosteroid-free at Week 54 (off corticosteroid for at least 24 weeks prior to Week 54) [ Time Frame: Week 54 ]
Percentage of participants with Adverse Events [ Time Frame: Baseline up to Week 217 ]
Pharmacokinetic: Etrolizumab Serum Concentration [ Time Frame: Predose (0 hour) at Week 2, 10, 12, 30, 54 ]
Percentage of participants achieving sustained clinical response sustained at Weeks 10, 30, and 54 [ Time Frame: Weeks 10,30, and 54 ]
Percentage of Participants with Improvement from Baseline in Endoscopic Appearance of the Mucosa at Week 54 [ Time Frame: Baseline to Week 54 ]
Percentage of Participants with Endoscopic Remission at Week 54 [ Time Frame: Week 54 ]
Percentage of Participants with sustained clinical remission at Weeks 10,30, and 54 [ Time Frame: Weeks 10,30, and 54 ]
Percentage of Participants with sustained clinical response at Weeks 10,30 and 54 [ Time Frame: Weeks 10,30, and 54 ]
Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at Weeks 10,30 and 54 [ Time Frame: Weeks 10,30 and 54 ]
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) [ Time Frame: Week 0,4,10,12,30 and 54 ]


Estimated Enrollment:	720
Actual Study Start Date:	April 15, 2014
Estimated Study Completion Date:	February 28, 2019
Estimated Primary Completion Date:	February 28, 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: etrolizumab + placebo (IV) Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV until Week 46	Drug: etrolizumab 105 mg administered by subcutaneous injection (Q4W) until Week 52 Other: placebo (IV) Administered by (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46.
Active Comparator: infliximab + placebo (injection) Participants will receive IV Infusion of Iinfliximab at Weeks 0,2, and 6, then every 8 weeks until Week 46 partnered with placebo matched to ertolizumab SC Q4W until Week 52	Drug: infliximab 5 mg/kg of infliximab will be administered by intravenous (IV) infusion at Weeks 0, 2, and 6 and then every 8 weeks until Week 46. Other: placebo (injection) administered by SC injection Q4W until Week 52

Eligibility


Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Moderately to severely active UC as determined by the Mayo Clinic Score assessment (MCS)
Naive to treatment with any anti-TNF therapy
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, and efalizumab)
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)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02136069

Contacts


Contact: Reference Study ID Number: GA29103 www.roche.com/about_roche/roche_worldwide.htm	888-662-6728 (U.S. and Canada)	global.rochegenentechtrials@roche.com

Show 249 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT02136069 History of Changes
Other Study ID Numbers:	GA29103 2013-004282-14 ( EudraCT Number )
Study First Received:	April 15, 2014
Last Updated:	March 31, 2017

Additional relevant MeSH terms:


Colitis Ulcer Colitis, Ulcerative Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Colonic Diseases	Intestinal Diseases Pathologic Processes Inflammatory Bowel Diseases Infliximab Dermatologic Agents Gastrointestinal Agents Antirheumatic Agents

ClinicalTrials.gov processed this record on August 21, 2017