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Trial record 2 of 4 for:    etrolizumab | Ulcerative Colitis | Italy

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)

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ClinicalTrials.gov Identifier: NCT02136069
Recruitment Status : Completed
First Posted : May 12, 2014
Last Update Posted : December 8, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE April 15, 2014
First Posted Date  ICMJE May 12, 2014
Last Update Posted Date December 8, 2020
Actual Study Start Date  ICMJE December 24, 2014
Actual Primary Completion Date June 23, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2018)
Percentage of Participants with Both Clinical Response at Week 10 and Clinical Remission at Week 54 [ Time Frame: Week 10, Week 54 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 8, 2014)
  • Proportion of patients in sustained clinical remission as determined by Mayo Clinic Score (MCS). Clinical remission is defined as MCS </=2 with individual subscores </=1. [ Time Frame: Week 10 ]
  • Proportion of patients in sustained clinical remission as determined by Mayo Clinic Score (MCS). Clinical remission is defined as MCS </=2 with individual subscores </=1. [ Time Frame: Week 54 ]
  • Proportion of patients in sustained clinical remission as determined by Mayo Clinic Score (MCS). Clinical remission is defined as MCS </=2 with individual subscores </=1. [ Time Frame: Week 30 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2020)
  • Percentage of Participants Achieving Clinical Remission at Week 10, Defined as Mayo Clinic Score (MCS) ≤2 with Individual Subscores ≤1 [ Time Frame: Week 10 ]
  • Percentage of Participants Achieving Clinical Remission at Week 54 [ Time Frame: Week 54 ]
  • Percentage of Participants Achieving Clinical Remission at Both Week 10 and Week 54 [ Time Frame: Week 10 and Week 54 ]
  • Percentage of Participants Achieving Clinical Remission at Week 54 Among Those with a Clinical Response at Week 10 [ Time Frame: Week 10 and Week 54 ]
  • Percentage of Participants with Improvement from Baseline in Endoscopic Appearance of the Mucosa at Week 10 [ Time Frame: Baseline to Week 10 ]
  • 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 Improvement from Baseline in Endoscopic Appearance of the Mucosa at Both Week 10 and Week 54 [ Time Frame: Baseline to Week 10, Week 54 ]
  • Percentage of Participants with Endoscopic Remission at Week 54 [ Time Frame: Week 54 ]
  • Percentage of Participants Achieving Clinical Response at Week 10, Defined as MCS with ≥3-point Decrease and 30% Reduction from Baseline as well as ≥1-point Decrease in Rectal Bleeding Subscore or an Absolute Rectal Bleeding Score of 0 or 1 [ Time Frame: Week 10 ]
  • Percentage of Participants Achieving Clinical Response at Both Weeks 10 and 54 [ Time Frame: Week 10, Week 54 ]
  • Percentage of Participants that Achieve Clinical Remission Corticosteroid-Free at Week 54 (off Corticosteroid for at Least 24 Weeks Prior to Week 54) Among Those Who Were Receiving Corticosteroids at Baseline [ Time Frame: Baseline and Week 54 ]
  • Number of Participants with Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) [ Time Frame: Baseline up to Week 54 ]
  • Number of Participants with Adverse Events Leading to Study Drug Discontinuation [ Time Frame: Baseline up to Week 54 ]
  • Number of Participants with Infection-Related Adverse Events, Severity Determined According to the NCI CTCAE v4.0 [ Time Frame: Baseline up to Week 54 ]
  • Number of Participants with Serious Infection-Related Adverse Events [ Time Frame: Baseline up to Week 54 ]
  • Number of Participants with Malignancies [ Time Frame: Baseline up to Week 54 ]
  • Number of Participants with Injection-Site Reactions, Severity Determined According to the NCI CTCAE v4.0 [ Time Frame: Baseline up to Week 54 ]
  • Number of Participants with Hypersensitivity Reaction Events, Severity Determined According to the NCI CTCAE v4.0 [ Time Frame: Baseline up to Week 54 ]
  • Pharmacokinetics: Etrolizumab Serum Concentration [ Time Frame: Predose (0 hour) at Weeks 2, 10, 12, 30, and 54 ]
  • Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Overall Score at Weeks 10, 30, and 54 [ Time Frame: Weeks 10, 30, and 54 ]
  • Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Etrolizumab or Infliximab [ Time Frame: Weeks 0, 4, 10, 12, 30, and 54 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2014)
  • Proportion of patients achieving clinical remission, defined as MCS </=2 with individual subscores </=1 [ Time Frame: Weeks 10 and 54 ]
  • Proportion of patients achieving clinical response, defined as MCS with >/=3-point decrease and 30% reduction from baseline as well as >/=1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1 [ Time Frame: Week 10 ]
  • Proportion of patients achieving sustained clinical response, defined by clinical response sustained at Weeks 10, 30, and 54 [ Time Frame: Up to 54 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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 Naive to TNF Inhibitors
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE
  • Drug: Etrolizumab
    105 mg administered by subcutaneous (SC) injection once every 4 weeks (Q4W) until Week 52.
    Other Names:
    • PRO145223
    • RO5490261
    • RG7413
  • 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 (IV)
    Administered by (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
Study Arms  ICMJE
  • Experimental: Etrolizumab + Placebo (IV)
    Participants will receive ertolizumab (SC) Q4W until Week 52 along with placebo matched to infliximab as IV infusion until Week 46.
    Interventions:
    • Drug: Etrolizumab
    • Other: Placebo (IV)
  • Active Comparator: Infliximab + Placebo (Injection)
    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.
    Interventions:
    • Drug: Infliximab
    • Other: Placebo (Injection)
Publications * Sandborn WJ, Vermeire S, Tyrrell H, Hassanali A, Lacey S, Tole S, Tatro AR; Etrolizumab Global Steering Committee. Etrolizumab for the Treatment of Ulcerative Colitis and Crohn's Disease: An Overview of the Phase 3 Clinical Program. Adv Ther. 2020 Jul;37(7):3417-3431. doi: 10.1007/s12325-020-01366-2. Epub 2020 May 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 14, 2020)
397
Original Estimated Enrollment  ICMJE
 (submitted: May 8, 2014)
720
Actual Study Completion Date  ICMJE June 23, 2020
Actual Primary Completion Date June 23, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   Austria,   Belgium,   Canada,   Czechia,   France,   Germany,   Hungary,   Israel,   Korea, Republic of,   Netherlands,   Norway,   Portugal,   Romania,   Singapore,   South Africa,   Spain,   Sweden,   Switzerland,   United Kingdom
Removed Location Countries Czech Republic,   Philippines,   Vietnam
 
Administrative Information
NCT Number  ICMJE NCT02136069
Other Study ID Numbers  ICMJE GA29103
2013-004282-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP