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A Study of the Efficacy and Safety of Etrolizumab Treatment in Maintenance of Disease Remission in Ulcerative Colitis (UC) Participants Who Are Naive to Tumor Necrosis Factor (TNF) Inhibitors (LAUREL)

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ClinicalTrials.gov Identifier: NCT02165215
Recruitment Status : Active, not recruiting
First Posted : June 17, 2014
Last Update Posted : April 26, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE June 13, 2014
First Posted Date  ICMJE June 17, 2014
Last Update Posted Date April 26, 2019
Actual Study Start Date  ICMJE August 12, 2014
Estimated Primary Completion Date April 21, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants with a Clinical Response at Week 10, as Determined by the Mayo Clinic Score (MCS) [ Time Frame: Week 62 ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 16, 2014)
Maintenance of remission among randomized patients in remission at Week 10 as determined by the Mayo Clinic Score (MCS) [ Time Frame: Week 62 ]
Change History Complete list of historical versions of study NCT02165215 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
  • Maintenance Phase: Percentage of Participants Who Maintained Clinical Remission at Week 62 Among Randomized Participants in Clinical Remission at Week 10, as Determined by the MCS [ Time Frame: Week 62 ]
  • Maintenance Phase: Percentage of Participants in Clinical Remission at Week 62, as Determined by the MCS [ Time Frame: Week 62 ]
  • Maintenance Phase: Percentage of Participants in Remission at Week 62 Among Randomized Participants in Remission at Week 10, as Determined by the MCS [ Time Frame: Week 62 ]
  • Maintenance Phase: Percentage of Participants with Improvement from Baseline in Endoscopic Appearance of the Mucosa at Week 62, as Determined by the MCS Endoscopic Subscore [ Time Frame: Baseline, Week 62 ]
  • Maintenance Phase: Percentage of Participants with Endoscopic Remission at Week 62, as Determined by the MCS Endoscopic Subscore [ Time Frame: Week 62 ]
  • Maintenance Phase: Percentage of Participants with Histologic Remission at Week 62, as Determined by the Nancy Histological Index [ Time Frame: Week 62 ]
  • Induction Phase: Change from Baseline to Week 6 in MCS Rectal Bleed Subscore [ Time Frame: Baseline, Week 6 ]
  • Induction Phase: Change from Baseline to Week 6 in MCS Stool Frequency Subscore [ Time Frame: Baseline, Week 6 ]
  • Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission at Week 62 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [ Time Frame: Baseline, Week 62 ]
  • Maintenance Phase: Percentage of Participants with Corticosteroid-Free Remission at Week 62 Among Participants Who Were Receiving Corticosteroids at Baseline, as Determined by the MCS [ Time Frame: Baseline, Week 62 ]
  • Maintenance Phase: Change from Baseline to Week 62 in UC Bowel Movement Signs and Symptoms, as Assessed by the Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Questionnaire [ Time Frame: Baseline, Week 62 ]
  • Maintenance Phase: Change from Baseline to Week 62 in UC Abdominal Symptoms, as Assessed by the UC-PRO/SS Questionnaire [ Time Frame: Baseline, Week 62 ]
  • Maintenance Phase: Change from Baseline to Week 62 in Health-Related Quality of Life, as Assessed by the Overall Score of the Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Baseline, Week 62 ]
  • Number of Participants with at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v4.0) [ Time Frame: From Baseline up to Week 74 ]
  • Number of Participants with Adverse Events Leading to Study Drug Discontinuation [ Time Frame: From Baseline up to Week 74 ]
  • Number of Participants with Serious Infection-Related Adverse Events [ Time Frame: From Baseline up to Week 74 ]
  • Number of Participants with Infection-Related Adverse Events by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 74 ]
  • Number of Participants with Injection-Site Reactions by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 74 ]
  • Number of Participants with Hypersensitivity Reaction Events by Severity, According to NCI-CTCAE v4.0 [ Time Frame: From Baseline up to Week 74 ]
  • Number of Participants with Malignancies [ Time Frame: From Baseline up to Week 74 ]
  • Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Etrolizumab [ Time Frame: Baseline, Weeks 4, 12, 24, 44, and 62, and and Early Termination/End of Safety Follow-Up (up to Week 74) ]
  • Etrolizumab Serum Trough Concentration [ Time Frame: Pre-dose (0 hour) at Baseline and Weeks 12, 24, 44, and 62 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2014)
  • Maintenance of clinical remission among randomized patients in clinical remission at Week 10 as determined by the MCS [ Time Frame: Week 62 ]
  • Clinical remission as determined by the MCS [ Time Frame: Week 62 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Efficacy and Safety of Etrolizumab Treatment in Maintenance of Disease Remission in Ulcerative Colitis (UC) Participants Who Are Naive to Tumor Necrosis Factor (TNF) Inhibitors
Official Title  ICMJE Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy (Maintenance of Remission) and Safety of Etrolizumab Compared With Placebo in Patients With Moderate to Severe Active Ulcerative Colitis Who Are Naive to TNF Inhibitors
Brief Summary This Phase III, randomized, double-blind, parallel-grouped, placebo-controlled, multicenter study will investigate the efficacy and safety of etrolizumab in maintenance of remission in participants with moderately to severely active UC who are naive to TNF inhibitors and refractory to or intolerant of prior immunosuppressant and/or corticosteroid treatment.
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 Colitis, Ulcerative
Intervention  ICMJE
  • Drug: Etrolizumab
    Participants will receive 105 mg etrolizumab SC injection Q4W.
    Other Names:
    • PRO145223
    • RO5490261
    • RG7413
  • Drug: Placebo
    Participants will receive placebo (matched to etrolizumab) SC injection Q4W.
Study Arms  ICMJE
  • Experimental: Open-Label Induction Phase: Etrolizumab
    All participants will receive treatment with open-label etrolizumab 105 milligrams (mg) subcutaneous (SC) injection once every 4 weeks (Q4W) up to Week 10.
    Intervention: Drug: Etrolizumab
  • Experimental: Double-Blind Maintenance Phase: Etrolizumab
    Participants who achieved a clinical response at Week 10 during the induction phase and randomized to this arm for the double-blind maintenance phase will receive etrolizumab 105 mg SC injection Q4W from Week 12 up to Week 62.
    Intervention: Drug: Etrolizumab
  • Placebo Comparator: Double-Blind Maintenance Phase: Placebo
    Participants who achieved a clinical response at Week 10 during the induction phase and randomized to this arm for the double-blind maintenance phase will receive placebo (matched to etrolizumab) SC injection Q4W from Week 12 up to Week 62.
    Intervention: Drug: Placebo
Publications * Not Provided

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 24, 2019)
359
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2014)
350
Estimated Study Completion Date  ICMJE July 21, 2020
Estimated Primary Completion Date April 21, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of ulcerative colitis (UC) established at least 3 months prior to Day 1 by clinical and endoscopic evidence
  • Moderately to severely active UC as determined by an MCS of 6-12 with an endoscopic subscore greater than or equal to (≥)2 as determined by the central reading procedure (endoscopy to be performed 4-16 days prior to Day 1), a rectal bleeding subscore ≥1, and a stool frequency subscore ≥1 during the screening period (prior to Day 1)
  • Evidence of UC extending a minimum of 20 centimeters (cm) from the anal verge as determined by baseline endoscopy (flexible sigmoidoscopy or colonoscopy) performed during screening, 4-16 days prior to Day 1
  • Naive to treatment with any anti-TNF therapy
  • Participants must have had an inadequate response, loss of response, or intolerance to prior corticosteroid and/or immunosuppressant treatment
  • Background regimen for UC may include oral 5-aminosalicylate (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
  • 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) as stated in the protocol
  • Any prior treatment with anti-adhesion molecules (such as mucosal addressin cell adhesion molecule [MAdCAM-1])
  • Any prior treatment with rituximab
  • Any treatment with tofacitinib during screening
  • Cogenital 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 within 60 days prior to Day 1 or 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
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 Brazil,   Canada,   Czechia,   Denmark,   Germany,   Hungary,   India,   Israel,   Italy,   Mexico,   Poland,   Slovakia,   South Africa,   Ukraine,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02165215
Other Study ID Numbers  ICMJE GA29102
2013-004280-31 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
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 April 2019

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