An Efficacy and Safety Study of Golimumab (CNTO 148) in Participants With Moderately to Severely Active Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT00487539
• Recruitment Status: Completed
• First Posted: June 18, 2007
• Results First Posted: February 17, 2014
• Last Update Posted: February 17, 2014
• Sponsor: Janssen Research & Development, LLC
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: June 14, 2007
• First Posted Date: June 18, 2007
• Results First Submitted Date: April 29, 2013
• Results First Posted Date: February 17, 2014
• Last Update Posted Date: February 17, 2014
• Study Start Date: August 2007
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2014)

Number of Participants With Clinical Response at Week 6 [ Time Frame: Baseline, Week 6 ]

Clinical response is defined as decrease from baseline in Mayo score by greater than or equal to 30 percent and greater than or equal to 3, with either a decrease from baseline in rectal bleeding sub-score of greater than or equal to 1 or a rectal bleeding sub-score of 0 or 1. The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings, and physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12.

• Original Primary Outcome Measures (submitted: June 14, 2007): Part 1:Evaluate the dose response; Select SC induction regimen(s) of CNTO 148 (golimumab), based on safety and efficacy; Part 2:Evaluate the safety and efficacy of SC induction regimens of CNTO 148 (golimumab) in inducing clinical response at Week 6.

Current Secondary Outcome Measures (submitted: January 14, 2014)

• Number of Participants With Clinical Remission at Week 6 [ Time Frame: Week 6 ]
  Clinical remission is defined as a Mayo score of less than or equal to 2, with no individual sub-score greater than 1. The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings, and physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12.
• Number of Participants With Mucosal Healing at Week 6 [ Time Frame: Week 6 ]
  Mucosal healing is determined from the endoscopy sub-score of the Mayo score. Mucosal healing is defined as an endoscopy sub-score of 0 or 1. Higher score indicates higher severity of disease. Endoscopy sub-score ranges from 0 (normal or inactive disease) to 3 (severe disease; spontaneous bleeding and ulceration).
• Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 [ Time Frame: Baseline to Week 6 ]
  The IBDQ is used to measure disease specific quality of life on a 32 Likert-scaled items questionnaire. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function and social function with scores ranging from 10 to 70, 5 to 35, 12 to 84 and 5 to 35 respectively and the total score ranges from 32 to 224. Higher scores indicate better health related quality of life.

• Original Secondary Outcome Measures (submitted: June 14, 2007): Evaluate the efficacy of SC induction regimens of CNTO 148 (golimumab) in inducing clinical remission, mucosal healing, improving disease-specific health-related quality of life at Week 6.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy and Safety Study of Golimumab (CNTO 148) in Participants With Moderately to Severely Active Ulcerative Colitis
• Official Title: A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Subcutaneously, in Subjects With Moderately to Severely Active Ulcerative Colitis
• Brief Summary: The purpose of this study is to assess the effects (good and bad) of golimumab (CNTO 148) therapy in participants with ulcerative colitis (UC).
• Detailed Description: This is a multi-center (conducted in more than one center), randomized (study medication assigned by chance), double-blind (neither the physician nor the participant know about the study medication), placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different interventions) study to evaluate the safety and efficacy of golimumab in participants with moderately to severely active UC. There are 2 parts in this study. Part 1 is "Phase 2 dose-ranging" portion of study. Participants enrolled in Part 1, will receive subcutaneous (under the skin by way of a needle) injections of placebo, golimumab 100 milligram (mg), 200 mg, or 400 mg at Week 0, followed by subcutaneous injections of placebo, golimumab 50 mg, 100 mg, or 200 mg respectively at Week 2. Part 2 is "Phase 3 dose-confirming" portion of study and newly enrolled participants will receive same doses studied in Part 1, until the doses for Part 2 are selected. At the time that the final doses are selected, all newly enrolled participants will receive 1 of the selected doses or matching placebo. At Week 6, participants will be asked to participate in an additional 1-year maintenance study. Participants not entering the 1-year golimumab maintenance study will be evaluated for safety 16 weeks after last administration of study agent. The duration of study will be 6 weeks for participants who enter the 1-year golimumab maintenance study and 16 weeks after last administration of study agent for participants who do not enter the 1-year golimumab maintenance study. Efficacy of the participants will primarily be evaluated by clinical response at Week 6. Participants' safety will be monitored throughout the study.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Colitis, Ulcerative

Intervention

• Biological: Placebo
  Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2.
• Biological: Golimumab 100 mg
  Golimumab 100 mg subcutaneous injection administered at Week 0 for Golimumab 100 mg -> 50 mg arm group and at Week 2 for Golimumab 200 mg -> 100 mg arm group.
• Biological: Golimumab 200 mg
  Golimumab 200 mg subcutaneous injection administered at Week 0 for Golimumab 200 mg -> 100 mg arm group and at Week 2 for Golimumab 400 mg -> 200 mg arm group.
• Biological: Golimumab 400 mg
  Golimumab 400 mg subcutaneous injection administered at Week 0 for Golimumab 400 mg -> 200 mg arm group.
• Biological: Golimumab 50 mg
  Golimumab 50 mg subcutaneous injection administered at Week 2 for Golimumab 100 mg -> 50 mg arm group.

Study Arms

• Placebo Comparator: Placebo
  Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2.
  Intervention: Biological: Placebo
• Experimental: Golimumab 100 mg -> 50 mg
  Golimumab 100 milligram (mg) subcutaneous injection administered at Week 0 and dose is decreased to 50 mg at Week 2.
  Interventions:

  • Biological: Golimumab 100 mg
  • Biological: Golimumab 50 mg
• Experimental: Golimumab 200 mg -> 100 mg
  Golimumab 200 mg subcutaneous injection administered at Week 0 and dose is decreased to 100 mg at Week 2.
  Interventions:

  • Biological: Golimumab 100 mg
  • Biological: Golimumab 200 mg
• Experimental: Golimumab 400 mg -> 200 mg
  Golimumab 400 mg subcutaneous injection administered at Week 0 and dose is decreased to 200 mg at Week 2.
  Interventions:

  • Biological: Golimumab 200 mg
  • Biological: Golimumab 400 mg

Publications *

• Adedokun OJ, Xu Z, Liao S, Strauss R, Reinisch W, Feagan BG, Sandborn WJ. Population Pharmacokinetics and Exposure-Response Modeling of Golimumab in Adults With Moderately to Severely Active Ulcerative Colitis. Clin Ther. 2020 Jan;42(1):157-174.e4. doi: 10.1016/j.clinthera.2019.11.010. Epub 2020 Jan 22.
• Li K, Strauss R, Marano C, Greenbaum LE, Friedman JR, Peyrin-Biroulet L, Brodmerkel C, De Hertogh G. A Simplified Definition of Histologic Improvement in Ulcerative Colitis and its Association With Disease Outcomes up to 30 Weeks from Initiation of Therapy: Post Hoc Analysis of Three Clinical Trials. J Crohns Colitis. 2019 Aug 14;13(8):1025-1035. doi: 10.1093/ecco-jcc/jjz022.
• Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel JF, Reinisch W, Gibson PR, Collins J, Jarnerot G, Hibi T, Rutgeerts P; PURSUIT-SC Study Group. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014 Jan;146(1):85-95; quiz e14-5. doi: 10.1053/j.gastro.2013.05.048. Epub 2013 Jun 2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 23, 2010): 1065
• Original Enrollment (submitted: June 14, 2007): 676
• Actual Study Completion Date: October 2010
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants diagnosed with moderately to severely active ulcerative colitis (UC) defined by a Mayo score of 6 to 12 inclusive at Baseline (Week 0), including an endoscopic (examination of an internal part of the body with a lighted tube; looking at a part of the body with a lighted tube) subscore of greater than or equal to 2
• Participants must have biopsy results (collected at the screening endoscopy (procedure or obtained within the last year) consistent with the diagnosis of UC
• Participants either currently receiving treatment with, or have a history of failure to respond to, or tolerate, at least 1 of the following therapies: oral 5-aminosalicylate, oral corticosteroids, 6-mercaptopurine and azathioprine
• Participants with current dependency or with a history of corticosteroid dependency (i.e., an inability to successfully taper corticosteroids without a return of the symptoms of UC)
• Not have a diagnosis of active tuberculosis
• Participants with negative stool test for enteric (by way of the intestines) pathogens

Exclusion Criteria:

• Participants with prior exposure to biologic anti-tumor necrosis factor (TNF) agents
• Participants with severe extensive UC that is likely to require a colectomy (surgery to remove part or all of the colon) within 12 weeks of study entry
• Participants having UC limited to the rectum only or to less than 20 centimeter of the colon
• Presence of a stoma (an artificial permanent opening especially in the abdominal wall made in surgical procedures) or presence of a fistula
• Participants with a history of extensive colonic resection

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, India, Israel, Japan, Lithuania, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Sweden, Ukraine, United States
• Removed Location Countries: Latvia, United Kingdom

Administrative Information

• NCT Number: NCT00487539
• Other Study ID Numbers: CR014176; C0524T17; 2006-003398-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Not Provided
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Centocor, Inc.
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: January 2014