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

NCT ID: NCT00487539

Last Updated: 2014-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 1065 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2010-10-31

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.

Conditions

Colitis, Ulcerative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2.

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.

Group Type: EXPERIMENTAL

Golimumab 100 mg

Intervention Type: BIOLOGICAL

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.

Golimumab 50 mg

Intervention Type: BIOLOGICAL

Golimumab 50 mg subcutaneous injection administered at Week 2 for Golimumab 100 mg -\> 50 mg arm group.

Golimumab 200 mg -> 100 mg

Golimumab 200 mg subcutaneous injection administered at Week 0 and dose is decreased to 100 mg at Week 2.

Group Type: EXPERIMENTAL

Golimumab 100 mg

Intervention Type: BIOLOGICAL

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.

Golimumab 200 mg

Intervention Type: BIOLOGICAL

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.

Golimumab 400 mg -> 200 mg

Golimumab 400 mg subcutaneous injection administered at Week 0 and dose is decreased to 200 mg at Week 2.

Group Type: EXPERIMENTAL

Golimumab 200 mg

Intervention Type: BIOLOGICAL

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.

Golimumab 400 mg

Intervention Type: BIOLOGICAL

Golimumab 400 mg subcutaneous injection administered at Week 0 for Golimumab 400 mg -\> 200 mg arm group.

Interventions

Placebo

Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Golimumab 400 mg

Golimumab 400 mg subcutaneous injection administered at Week 0 for Golimumab 400 mg -\> 200 mg arm group.

Intervention Type: BIOLOGICAL

Golimumab 50 mg

Golimumab 50 mg subcutaneous injection administered at Week 2 for Golimumab 100 mg -\> 50 mg arm group.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Little Rock, Arkansas, United States

Roseville, California, United States

San Diego, California, United States

Golden, Colorado, United States

Newark, Delaware, United States

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

Atlanta, Georgia, United States

Savannah, Georgia, United States

Arlington Heights, Illinois, United States

Chicago, Illinois, United States

Clive, Iowa, United States

Pratt, Kansas, United States

Lexington, Kentucky, United States

Monroe, Louisiana, United States

Ann Arbor, Michigan, United States

Troy, Michigan, United States

Rochester, Minnesota, United States

Pascagoula, Mississippi, United States

Tupelo, Mississippi, United States

Egg Harbor, New Jersey, United States

New York, New York, United States

Rochester, New York, United States

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

Fargo, North Dakota, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Colombus, Ohio, United States

Norman, Oklahoma, United States

Portland, Oregon, United States

Limerick, Pennsylvania, United States

Columbia, South Carolina, United States

Germantown, Tennessee, United States

Nashville, Tennessee, United States

Houston, Texas, United States

Sugar Land, Texas, United States

Logan, Utah, United States

Ogden, Utah, United States

Chesapeake, Virginia, United States

Fairfax, Virginia, United States

Richmond, Virginia, United States

Spokane, Washington, United States

Tacoma, Washington, United States

Madison, Wisconsin, United States

Milwaukee, Wisconsin, United States

Bankstown, , Australia

Box Hill, , Australia

Fitzroy, , Australia

Herston, , Australia

Launceston, , Australia

Parkville, , Australia

Prahran, , Australia

Westmead, , Australia

Vienna, , Austria

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Liège, , Belgium

Roeselare, , Belgium

Pleven, , Bulgaria

Rousse, , Bulgaria

Sofia, , Bulgaria

Vancouver, British Columbia, Canada

Barrie, Ontario, Canada

Chatham, Ontario, Canada

London, Ontario, Canada

Toronto, Ontario, Canada

Saskatoon, Saskatchewan, Canada

T2n, , Canada

Windsor, , Canada

Èeské Budìjovice 1, , Czechia

Hradec Králové, , Czechia

Litoměřice, , Czechia

Ostrava, , Czechia

Aalborg, , Denmark

Aarhus C, , Denmark

Hvidovre, , Denmark

Odense C, , Denmark

Amiens Cedex 1 80, , France

Bordeaux, , France

Lille, , France

Nice, , France

Paris, , France

Berlin, , Germany

Berlin Be, , Germany

Bochum, , Germany

Hamburg, , Germany

Hanover, , Germany

Haßloch, , Germany

Kiel, , Germany

Minden, , Germany

München, , Germany

Münster, , Germany

Stade, , Germany

Balatonfüred, , Hungary

Budapest, , Hungary

Debrecen, , Hungary

Dunaújváros, , Hungary

Gyulai Ut 18, , Hungary

Mosonmagyaróvár, , Hungary

Sopron, , Hungary

Szeged, , Hungary

Szekszárd, , Hungary

Székesfehérvár, , Hungary

Veszprém, , Hungary

Bangalore, , India

Chennai, , India

Hyderabad, , India

Hyderabad Andh Prad, , India

Kārnād, , India

New Delhi, , India

Pune, , India

Vishakapatanam, , India

Beer Yaakov, , Israel

Beersheba, , Israel

Haifa, , Israel

Jerusalem, , Israel

Kfar Saba, , Israel

Nazareth, , Israel

Petah-Tikv, , Israel

Rehovot, , Israel

Tel Aviv, , Israel

Bunkyō City, , 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

Tokyo, , Japan

Yokkaichi, , Japan

Kaunas, , Lithuania

Vilnius, , Lithuania

Amsterdam, , Netherlands

Ede Gld, , Netherlands

Groningen, , Netherlands

Leiden, , Netherlands

Christchurch, , New Zealand

Dunedin, , New Zealand

Hamilton, , New Zealand

Bydgoszcz, , Poland

Częstochowa, , Poland

Elblag, , Poland

Gdansk, , Poland

Krakow, , Poland

Lodz, , Poland

Lublin, , Poland

Opole, , Poland

Sopot, , Poland

Szczecin, , Poland

Torun, , Poland

Warsaw, , Poland

Bucharest, , Romania

Cluj-Napoca, , Romania

Iași, , Romania

Târgu Mureş, , Romania

Timișoara, , Romania

Moscow, , Russia

Novosibirsk, , Russia

Omsk, , Russia

Saint Petersburg, , Russia

Yaroslavl, , Russia

Belgrade, , Serbia

Niš, , Serbia

Zemun, , Serbia

Bratislava, , Slovakia

Martin, , Slovakia

Nitra, , Slovakia

Nové Mesto nad Váhom, , Slovakia

Prešov, , Slovakia

Cape Town, , South Africa

Cape Town West Cape, , South Africa

Marianhill Kz-Natal, , South Africa

Pretoria Gauteng, , South Africa

Stockholm, , Sweden

Donetsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Simferopol, , Ukraine

Vynnytsya, , Ukraine

Zhaporozhia 69104, , Ukraine

Countries

United States; Australia; Austria; Belgium; Bulgaria; Canada; Czechia; Denmark; France; Germany; Hungary; India; Israel; Japan; Lithuania; Netherlands; New Zealand; Poland; Romania; Russia; Serbia; Slovakia; South Africa; Sweden; Ukraine

References

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.

Reference Type: DERIVED

PMID: 31982148 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30721964 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23735746 (View on PubMed)

Other Identifiers

C0524T17

Identifier Type: -

Identifier Source: secondary_id

2006-003398-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NCT00487539

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR014176

Identifier Type: -

Identifier Source: org_study_id