Clinical trial NCT00109408: A Study to Assess the Safety and Efficacy of Tocilizumab in Patients With Active Rheumatoid Arthritis
Official title: A Randomized, Double-blind Study of Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab Monotherapy Versus Methotrexate Monotherapy in Patients With Moderate to Severe Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2005-04-28
Enrollment: 673
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: This 2 arm study will assess the safety and efficacy of tocilizumab monotherapy versus methotrexate in patients with active rheumatoid arthritis (RA). Patients will be randomized to receive tocilizumab 8mg/kg iv every 4 weeks plus placebo po weekly, or methotrexate 7.5-20mg po weekly plus placebo iv every 4 weeks. The anticipated time on study treatment is 3-12 months and the target sample size is 500+ individuals.


Eligibility criteria: Inclusion Criteria:

* adult patients at least 18 years of age with active RA for at least 3 months;
* patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria:

* major surgery (including joint surgery) within 8 weeks before entering study or planned major surgery within 6 months after entering study;
* treatment with methotrexate (MTX) within 6 months of entering study;
* patients who have stopped previous MTX treatment due to toxicity or lack of response;
* women who are pregnant or breast-feeding.

Primary outcomes:
measure: Percentage of patients with ACR 20 response
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of patients with ACR 20 response
timeFrame: Week 8
measure: Percentage of patients with ACR 50 and ACR 70 responses
timeFrame: Week 24
measure: Mean change in parameters of ACR core set
timeFrame: Week 24
measure: AEs, laboratory parameters, vital signs.
timeFrame: Throughout study
Other outcomes:
Locations:
city: Montgomery
country: United States
state: Alabama
city: Mesa
country: United States
state: Arizona
city: Paradise Valley
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Huntington Beach
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palm Springs
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Leandro
country: United States
state: California
city: Santa Maria
country: United States
state: California
city: Jupiter
country: United States
state: Florida
city: Palm Habor
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Idaho Falls
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Morton Grove
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Cedar Rapids
country: United States
state: Iowa
city: Des Moines
country: United States
state: Iowa
city: Bowling Green
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Slidell
country: United States
state: Louisiana
city: Greenbelt
country: United States
state: Maryland
city: Pittsfield
country: United States
state: Massachusetts
city: Grand Rapids
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Eagan
country: United States
state: Minnesota
city: St Cloud
country: United States
state: Minnesota
city: Flowood
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Dover
country: United States
state: New Hampshire
city: Nashua
country: United States
state: New Hampshire
city: Haddon Heights
country: United States
state: New Jersey
city: New Brunswick
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Fayetteville
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Mayfield
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Willow Grove
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Hickory
country: United States
state: South Carolina
city: Hixson
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Mesquite
country: United States
state: Texas
city: Chesapeake
country: United States
state: Virginia
city: Mountlake Terrace
country: United States
state: Washington
city: Olympia
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Yakima
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Florencio Varela
country: Argentina
city: Rosario
country: Argentina
city: Adelaide
country: Australia
city: Hobart
country: Australia
city: Shenton Park
country: Australia
city: Sydney
country: Australia
city: Woodville
country: Australia
city: Woolloongabba
country: Australia
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Winnipeg
country: Canada
state: Manitoba
city: St John's
country: Canada
state: Newfoundland and Labrador
city: Burlington
country: Canada
state: Ontario
city: Hamilton
country: Canada
state: Ontario
city: Kitchener
country: Canada
state: Ontario
city: Mississauga
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Guangzhou
country: China
city: Hefei Anhui
country: China
city: Jinan
country: China
city: Hillerod
country: Denmark
city: Hvidovre
country: Denmark
city: København
country: Denmark
city: Brest
country: France
city: Lyon
country: France
city: Paris
country: France
city: Rouen
country: France
city: Ashkelon
country: Israel
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Kfar Saba
country: Israel
city: Ramat Gan
country: Israel
city: Rishon Lezion
country: Israel
city: Genova
country: Italy
city: Milano
country: Italy
city: Pavia
country: Italy
city: Reggio Emilia
country: Italy
city: Siena
country: Italy
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Panevezys
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Guadalajara
country: Mexico
city: Guadalajara
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico City
country: Mexico
city: Mexico City
country: Mexico
city: Mexico City
country: Mexico
city: Levanger
country: Norway
city: Lillehammer
country: Norway
city: Lima
country: Peru
city: Lima
country: Peru
city: Almada
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Belgrade
country: Serbia
city: Niska Banja
country: Serbia
city: Ljubljana
country: Slovenia
city: Maribor
country: Slovenia
city: Cape Town
country: South Africa
city: Cape Town
country: South Africa
city: Diepkloof
country: South Africa
city: Pinelands
country: South Africa
city: Radiokop
country: South Africa
city: Alcorcon
country: Spain
city: Barcelona
country: Spain
city: Córdoba
country: Spain
city: Guadalajara
country: Spain
city: La Laguna
country: Spain
city: Lugo
country: Spain
city: Salamanca
country: Spain
city: Santiago de Compostela
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Drobinski PJ, Bay-Jensen AC, Karsdal MA, Sardar S, Siebuhr AS. Connective tissue remodelling is differently modulated by tocilizumab versus methotrexate monotherapy in patients with early rheumatoid arthritis: the AMBITION study. Arthritis Res Ther. 2021 Jan 7;23(1):13. doi: 10.1186/s13075-020-02378-7.
citation: Strand V, Michalska M, Birchwood C, Pei J, Tuckwell K, Finch R, Gabay C, Kavanaugh A, Jones G. Impact of tocilizumab monotherapy on patient-reported outcomes in patients with rheumatoid arthritis from two randomised controlled trials. RMD Open. 2017 Sep 14;3(2):e000496. doi: 10.1136/rmdopen-2017-000496. eCollection 2017.
citation: Jones G, Wallace T, McIntosh MJ, Brockwell L, Gomez-Reino JJ, Sebba A. Five-year Efficacy and Safety of Tocilizumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Methotrexate- and Biologic-naive or Free of Methotrexate for 6 Months: the AMBITION Study. J Rheumatol. 2017 Feb;44(2):142-146. doi: 10.3899/jrheum.160287. Epub 2016 Dec 1.
citation: Wang J, Bansal AT, Martin M, Germer S, Benayed R, Essioux L, Lee JS, Begovich A, Hemmings A, Kenwright A, Taylor KE, Upmanyu R, Cutler P, Harari O, Marchini J, Criswell LA, Platt A. Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.
citation: Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, Genovese MC. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010 Jan;69(1):88-96. doi: 10.1136/ard.2008.105197.