Clinical trial NCT00487539: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Colitis, Ulcerative
Keywords: Colitis, Ulcerative
Golimumab
CNTO 148
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2007-06-18
Enrollment: 1065
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Clinical Response at Week 6
timeFrame: Baseline, Week 6
Secondary outcomes:
measure: Number of Participants With Clinical Remission at Week 6
timeFrame: Week 6
measure: Number of Participants With Mucosal Healing at Week 6
timeFrame: Week 6
measure: Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6
timeFrame: Baseline to Week 6
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Little Rock
country: United States
state: Arkansas
city: Roseville
country: United States
state: California
city: San Diego
country: United States
state: California
city: Golden
country: United States
state: Colorado
city: Newark
country: United States
state: Delaware
city: Boca Raton
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Naples
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Zephyrhills
country: United States
state: Florida
city: Atlanta
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state: Georgia
city: Savannah
country: United States
state: Georgia
city: Arlington Heights
country: United States
state: Illinois
city: Chicago
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state: Illinois
city: Clive
country: United States
state: Iowa
city: Pratt
country: United States
state: Kansas
city: Lexington
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state: Kentucky
city: Monroe
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state: Louisiana
city: Ann Arbor
country: United States
state: Michigan
city: Troy
country: United States
state: Michigan
city: Rochester
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state: Minnesota
city: Pascagoula
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
city: Egg Harbor Township
country: United States
state: New Jersey
city: New York
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state: New York
city: Rochester
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state: New York
city: Asheville
country: United States
state: North Carolina
city: Charlotte
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state: North Carolina
city: Morganton
country: United States
state: North Carolina
city: New Bern
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state: North Carolina
city: Raleigh
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city: Wilmington
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city: Winston Salem
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state: North Carolina
city: Fargo
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state: North Dakota
city: Cincinnati
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state: Ohio
city: Cleveland
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state: Ohio
city: Colombus
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state: Oklahoma
city: Portland
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state: Pennsylvania
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state: South Carolina
city: Germantown
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state: Tennessee
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state: Tennessee
city: Houston
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state: Texas
city: Sugar Land
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state: Texas
city: Logan
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state: Utah
city: Ogden
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state: Utah
city: Chesapeake
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state: Virginia
city: Fairfax
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state: Virginia
city: Richmond
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state: Virginia
city: Spokane
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state: Washington
city: Tacoma
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state: Washington
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state: Wisconsin
city: Milwaukee
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city: Bankstown
country: Australia
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city: Herston
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city: Launceston
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city: Parkville
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city: Prahran
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city: Westmead
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city: Wien N/A
country: Austria
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Roeselare
country: Belgium
city: Pleven
country: Bulgaria
city: Rousse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Vancouver
country: Canada
state: British Columbia
city: Barrie
country: Canada
state: Ontario
city: Chatham
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state: Ontario
city: London
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city: Toronto
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city: Saskatoon
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state: Saskatchewan
city: T2n
country: Canada
city: Windsor
country: Canada
city: Hradec Kralove
country: Czech Republic
city: Litomerice
country: Czech Republic
city: Ostrava
country: Czech Republic
city: Èeské Budìjovice 1
country: Czech Republic
city: Aalborg
country: Denmark
city: Aarhus C.
country: Denmark
city: Hvidovre
country: Denmark
city: Odense C
country: Denmark
city: Amiens Cedex 1 80
country: France
city: Bordeaux 33
country: France
city: Lille Cedex
country: France
city: Nice Cedex 3
country: France
city: Paris
country: France
city: Berlin Be
country: Germany
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Haßloch
country: Germany
city: Kiel
country: Germany
city: Minden
country: Germany
city: Muenchen
country: Germany
city: Münster
country: Germany
city: Stade
country: Germany
city: Balatonfured
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Dunaujvaros
country: Hungary
city: Gyulai Ut 18
country: Hungary
city: Mosonmagyarovar
country: Hungary
city: Sopron
country: Hungary
city: Szeged
country: Hungary
city: Szekesfehervar
country: Hungary
city: Szekszard
country: Hungary
city: Veszprém
country: Hungary
city: Bangalore
country: India
city: Chennai
country: India
city: Hyderabad Andh Prad
country: India
city: Hyderabad
country: India
city: Karnad
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Vishakapatanam
country: India
city: Beer Sheva
country: Israel
city: Beer Yaakov
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Nazareth
country: Israel
city: Petah-Tikv
country: Israel
city: Rechovot
country: Israel
city: Tel-Aviv
country: Israel
city: Bunkyo-Ku
country: Japan
city: Bunkyo
country: Japan
city: Chikushinoshi
country: Japan
city: Fukuoka
country: Japan
city: Hiroshima
country: Japan
city: Kagoshima
country: Japan
city: Kurashiki
country: Japan
city: Kurume
country: Japan
city: Nagoya
country: Japan
city: Nishinomiya
country: Japan
city: Okayama
country: Japan
city: Osaka
country: Japan
city: Sakura
country: Japan
city: Sapporo-Shi
country: Japan
city: Sapporo
country: Japan
city: Tokyo
country: Japan
city: Yokkaichi
country: Japan
city: Kaunas
country: Lithuania
city: Vilnius
country: Lithuania
city: Amsterdam
country: Netherlands
city: Ede Gld
country: Netherlands
city: Groningen
country: Netherlands
city: Leiden
country: Netherlands
city: Christchurch
country: New Zealand
city: Dunedin
country: New Zealand
city: Hamilton
country: New Zealand
city: Bydgoszcz N/A
country: Poland
city: Czestochowa
country: Poland
city: Elblag
country: Poland
city: Gdansk
country: Poland
city: Krakow N/A
country: Poland
city: Krakow
country: Poland
city: Kraków N/A
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Opole N/A
country: Poland
city: Sopot
country: Poland
city: Szczecin
country: Poland
city: Torun
country: Poland
city: Warszawa N/A
country: Poland
city: Warszawa
country: Poland
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Targu Mures
country: Romania
city: Timisoara
country: Romania
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Omsk
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Belgrade
country: Serbia
city: Belgrado
country: Serbia
city: Nis
country: Serbia
city: Zemun
country: Serbia
city: Bratislava
country: Slovakia
city: Martin
country: Slovakia
city: Nitra
country: Slovakia
city: Nove Mesto Nad Vahom
country: Slovakia
city: Presov
country: Slovakia
city: Cape Town West Cape
country: South Africa
city: Cape Town
country: South Africa
city: Marianhill Kz-Natal
country: South Africa
city: Pretoria Gauteng
country: South Africa
city: Stockholm
country: Sweden
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Simferopol
country: Ukraine
city: Vynnytsya
country: Ukraine
city: Zhaporozhia 69104
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.