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

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

The purpose of this study is to assess the effects (good and bad) of golimumab (CNTO 148) therapy in participants with ulcerative colitis (UC).

Study Overview

• Status: Completed
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Biological: Placebo; Biological: Golimumab 100 mg; Biological: Golimumab 50 mg; Biological: Golimumab 200 mg; Biological: Golimumab 400 mg

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
• Enrollment (Actual): 1065
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bankstown, Australia
  • Box Hill, Australia
  • Fitzroy, Australia
  • Herston, Australia
  • Launceston, Australia
  • Parkville, Australia
  • Prahran, Australia
  • Westmead, Australia
• Austria
  • Wien N/A, Austria
• Belgium
  • Brussels, Belgium
  • Gent, Belgium
  • Leuven, Belgium
  • Liege, Belgium
  • Roeselare, Belgium
• Bulgaria
  • Pleven, Bulgaria
  • Rousse, Bulgaria
  • Sofia, Bulgaria
• Canada
  • T2n, Canada
  • Windsor, Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Ontario
    • Barrie, Ontario, Canada
    • Chatham, Ontario, Canada
    • London, Ontario, Canada
    • Toronto, Ontario, Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
• Czech Republic
  • Hradec Kralove, Czech Republic
  • Litomerice, Czech Republic
  • Ostrava, Czech Republic
  • Èeské Budìjovice 1, Czech Republic
• Denmark
  • Aalborg, Denmark
  • Aarhus C., Denmark
  • Hvidovre, Denmark
  • Odense C, Denmark
• France
  • Amiens Cedex 1 80, France
  • Bordeaux 33, France
  • Lille Cedex, France
  • Nice Cedex 3, France
  • Paris, France
• Germany
  • Berlin, Germany
  • Berlin Be, Germany
  • Bochum, Germany
  • Hamburg, Germany
  • Hannover, Germany
  • Haßloch, Germany
  • Kiel, Germany
  • Minden, Germany
  • Muenchen, Germany
  • Münster, Germany
  • Stade, Germany
• Hungary
  • Balatonfured, Hungary
  • Budapest, Hungary
  • Debrecen, Hungary
  • Dunaujvaros, Hungary
  • Gyulai Ut 18, Hungary
  • Mosonmagyarovar, Hungary
  • Sopron, Hungary
  • Szeged, Hungary
  • Szekesfehervar, Hungary
  • Szekszard, Hungary
  • Veszprém, Hungary
• India
  • Bangalore, India
  • Chennai, India
  • Hyderabad, India
  • Hyderabad Andh Prad, India
  • Karnad, India
  • New Delhi, India
  • Pune, India
  • Vishakapatanam, India
• Israel
  • Beer Sheva, Israel
  • Beer Yaakov, Israel
  • Haifa, Israel
  • Jerusalem, Israel
  • Kfar Saba, Israel
  • Nazareth, Israel
  • Petah-Tikv, Israel
  • Rechovot, Israel
  • Tel-Aviv, Israel
• Japan
  • Bunkyo, Japan
  • Bunkyo-Ku, Japan
  • Chikushinoshi, Japan
  • Fukuoka, Japan
  • Hiroshima, Japan
  • Kagoshima, Japan
  • Kurashiki, Japan
  • Kurume, Japan
  • Nagoya, Japan
  • Nishinomiya, Japan
  • Okayama, Japan
  • Osaka, Japan
  • Sakura, Japan
  • Sapporo, Japan
  • Sapporo-Shi, Japan
  • Tokyo, Japan
  • Yokkaichi, Japan
• Lithuania
  • Kaunas, Lithuania
  • Vilnius, Lithuania
• Netherlands
  • Amsterdam, Netherlands
  • Ede Gld, Netherlands
  • Groningen, Netherlands
  • Leiden, Netherlands
• New Zealand
  • Christchurch, New Zealand
  • Dunedin, New Zealand
  • Hamilton, New Zealand
• Poland
  • Bydgoszcz N/A, Poland
  • Czestochowa, Poland
  • Elblag, Poland
  • Gdansk, Poland
  • Krakow, Poland
  • Krakow N/A, Poland
  • Kraków N/A, Poland
  • Lodz, Poland
  • Lublin, Poland
  • Opole N/A, Poland
  • Sopot, Poland
  • Szczecin, Poland
  • Torun, Poland
  • Warszawa, Poland
  • Warszawa N/A, Poland
• Romania
  • Bucuresti, Romania
  • Cluj-Napoca, Romania
  • Iasi, Romania
  • Targu Mures, Romania
  • Timisoara, Romania
• Russian Federation
  • Moscow, Russian Federation
  • Novosibirsk, Russian Federation
  • Omsk, Russian Federation
  • Saint Petersburg, Russian Federation
  • St Petersburg, Russian Federation
  • St-Petersburg, Russian Federation
  • Yaroslavl, Russian Federation
• Serbia
  • Belgrade, Serbia
  • Belgrado, Serbia
  • Nis, Serbia
  • Zemun, Serbia
• Slovakia
  • Bratislava, Slovakia
  • Martin, Slovakia
  • Nitra, Slovakia
  • Nove Mesto Nad Vahom, Slovakia
  • Presov, Slovakia
• South Africa
  • Cape Town, South Africa
  • Cape Town West Cape, South Africa
  • Marianhill Kz-Natal, South Africa
  • Pretoria Gauteng, South Africa
• Sweden
  • Stockholm, Sweden
• Ukraine
  • Donetsk, Ukraine
  • Kharkiv, Ukraine
  • Kyiv, Ukraine
  • Simferopol, Ukraine
  • Vynnytsya, Ukraine
  • Zhaporozhia 69104, Ukraine
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Roseville, California, United States
    • San Diego, California, United States
  • Colorado
    • Golden, Colorado, United States
  • Delaware
    • Newark, Delaware, United States
  • Florida
    • Boca Raton, Florida, United States
    • Gainesville, Florida, United States
    • Hialeah, Florida, United States
    • Naples, Florida, United States
    • New Port Richey, Florida, United States
    • Port Orange, Florida, United States
    • Winter Park, Florida, United States
    • Zephyrhills, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Savannah, Georgia, United States
  • Illinois
    • Arlington Heights, Illinois, United States
    • Chicago, Illinois, United States
  • Iowa
    • Clive, Iowa, United States
  • Kansas
    • Pratt, Kansas, United States
  • Kentucky
    • Lexington, Kentucky, United States
  • Louisiana
    • Monroe, Louisiana, United States
  • Michigan
    • Ann Arbor, Michigan, United States
    • Troy, Michigan, United States
  • Minnesota
    • Rochester, Minnesota, United States
  • Mississippi
    • Pascagoula, Mississippi, United States
    • Tupelo, Mississippi, United States
  • New Jersey
    • Egg Harbor Township, New Jersey, United States
  • New York
    • New York, New York, United States
    • Rochester, New York, United States
  • North Carolina
    • Asheville, North Carolina, United States
    • Charlotte, North Carolina, United States
    • Morganton, North Carolina, United States
    • New Bern, North Carolina, United States
    • Raleigh, North Carolina, United States
    • Wilmington, North Carolina, United States
    • Winston Salem, North Carolina, United States
  • North Dakota
    • Fargo, North Dakota, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
    • Colombus, Ohio, United States
  • Oklahoma
    • Norman, Oklahoma, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Limerick, Pennsylvania, United States
  • South Carolina
    • Columbia, South Carolina, United States
  • Tennessee
    • Germantown, Tennessee, United States
    • Nashville, Tennessee, United States
  • Texas
    • Houston, Texas, United States
    • Sugar Land, Texas, United States
  • Utah
    • Logan, Utah, United States
    • Ogden, Utah, United States
  • Virginia
    • Chesapeake, Virginia, United States
    • Fairfax, Virginia, United States
    • Richmond, Virginia, United States
  • Washington
    • Spokane, Washington, United States
    • Tacoma, Washington, United States
  • Wisconsin
    • Madison, Wisconsin, United States
    • Milwaukee, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: Placebo; Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2.
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.	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 50 mg; Golimumab 50 mg subcutaneous injection administered at Week 2 for Golimumab 100 mg -> 50 mg arm group.
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.	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.
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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinical Response at 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.	Baseline, Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinical Remission at 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.	Week 6
Number of Participants With Mucosal Healing at 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).	Week 6
Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at 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.	Baseline to Week 6

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: June 14, 2007
• First Submitted That Met QC Criteria: June 14, 2007
• First Posted (Estimate): June 18, 2007

Study Record Updates

• Last Update Posted (Estimate): February 17, 2014
• Last Update Submitted That Met QC Criteria: January 14, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Golimumab; Colitis, Ulcerative; CNTO 148
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal; Golimumab
• Other Study ID Numbers: CR014176; C0524T17; 2006-003398-28 (EudraCT Number); NCT00487539 (Registry Identifier: ClinicalTrials.gov Identifier)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No