A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis

NCT00106548 | Completed Phase 3

• 1 other identifier: WA17822
• Study Type: interventional
• Target: 623
• Locations: 16 countries
• Sites: 70

Brief Summary

This 3 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with methotrexate (MTX). in patients with moderate to severe active rheumatoid arthritis (RA) who currently have an inadequate response to MTX. Patients wil be randomized to receive tocilizumab 4mg/kg iv, tocilizumab 8mg/mg iv, or placebo iv, every 4 weeks; all patients will also receive methotrexate 10-25mg weekly. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with ACR 20 response

  Week 24

Secondary Outcomes (2)

• Percentage of patients ACR 50/70 responses; change from baseline in ACR core set components.

  Week 24

• AEs, laboratory parameters, vital signs

  Throughout study

Study Arms (3)

1

EXPERIMENTAL

Drug: tocilizumab [RoActemra/Actemra]; Drug: Methotrexate

2

EXPERIMENTAL

Drug: tocilizumab [RoActemra/Actemra]; Drug: Methotrexate

3

PLACEBO COMPARATOR

Drug: Placebo; Drug: Methotrexate

Interventions

tocilizumab [RoActemra/Actemra] DRUG

4mg/kg iv / month

1

Placebo DRUG

iv / month

3

Methotrexate DRUG

10-25mg/week

1; 2; 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult patients at least 18 years of age with moderate to severe active RA for at least 6 months;
• inadequate response to a stable dose of MTX;
• patients of reproductive potential must be using reliable methods of contraception.

You may not qualify if:

• major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
• prior treatment failure with an anti-tumor necrosis factor agent;
• women who are pregnant or breast-feeding.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (74)

Unknown Facility

Buenos Aires, 1405, Argentina

Location

Unknown Facility

Buenos Aires, C1015ABO, Argentina

Location

Unknown Facility

Buenos Aires, C1428CQG, Argentina

Location

Unknown Facility

Adelaide, 5041, Australia

Location

Unknown Facility

Douglas, 4184, Australia

Location

Unknown Facility

Maroochydore, 4558, Australia

Location

Unknown Facility

Shenton Park, 6008, Australia

Location

Unknown Facility

Vienna, 1090, Austria

Location

Unknown Facility

Vienna, 1100, Austria

Location

Unknown Facility

Vienna, 1130, Austria

Location

Unknown Facility

Vienna, 1160, Austria

Location

Unknown Facility

Porto Alegre, 91350-200, Brazil

Location

Unknown Facility

São Paulo, 05651-901, Brazil

Location

Unknown Facility

Sofia, 1606, Bulgaria

Location

Unknown Facility

Sofia, 1784, Bulgaria

Location

Unknown Facility

Varna, 9010, Bulgaria

Location

Unknown Facility

Calgary, Alberta, T2N 4N1, Canada

Location

Unknown Facility

Vancouver, British Columbia, V5Z 1L7, Canada

Location

Unknown Facility

Victoria, British Columbia, V8V 3P9, Canada

Location

Unknown Facility

Winnipeg, Manitoba, R3A 1M3, Canada

Location

Unknown Facility

St. John's, Newfoundland and Labrador, A1B 3E1, Canada

Location

Unknown Facility

Burlington, Ontario, L7M 4Y1, Canada

Location

Unknown Facility

Newmarket, Ontario, L3Y 3R7, Canada

Location

Unknown Facility

Ottawa, Ontario, K1H 1A2, Canada

Location

Unknown Facility

Toronto, Ontario, M4N 3M5, Canada

Location

Unknown Facility

Montreal, Quebec, H1T 4B3, Canada

Location

Unknown Facility

Montreal, Quebec, H2L 1S6, Canada

Location

Unknown Facility

Sainte-Foy, Quebec, G1W 4R4, Canada

Location

Unknown Facility

Hong Kong, 852, China

Location

Unknown Facility

Hong Kong, China

Location

Unknown Facility

Besançon, 25030, France

Location

Unknown Facility

Créteil, 94010, France

Location

Unknown Facility

Le Mans, 72000, France

Location

Unknown Facility

Montpellier, 34295, France

Location

Unknown Facility

Paris, 75010, France

Location

Unknown Facility

Paris, 75012, France

Location

Unknown Facility

Paris, 75014, France

Location

Unknown Facility

Bad Bramstedt, 24576, Germany

Location

Unknown Facility

Bad Nauheim, 61231, Germany

Location

Unknown Facility

Baden-Baden, 76530, Germany

Location

Unknown Facility

Berlin, 14059, Germany

Location

Unknown Facility

Cologne, 50924, Germany

Location

Unknown Facility

Erlangen, 91056, Germany

Location

Unknown Facility

Heidelberg, 69120, Germany

Location

Unknown Facility

Tübingen, 72076, Germany

Location

Unknown Facility

Budapest, 1023, Hungary

Location

Unknown Facility

Debrecen, 4004, Hungary

Location

Unknown Facility

Pécs, 7632, Hungary

Location

Unknown Facility

Beersheba, 84101, Israel

Location

Unknown Facility

Haifa, 31048, Israel

Location

Unknown Facility

Haifa, 31096, Israel

Location

Unknown Facility

Jerusalem, 91120, Israel

Location

Unknown Facility

Petah Tikva, 49100, Israel

Location

Unknown Facility

Tel Aviv, 64239, Israel

Location

Unknown Facility

Ferrara, 44100, Italy

Location

Unknown Facility

Gazzi, 98125, Italy

Location

Unknown Facility

Palermo, 90127, Italy

Location

Unknown Facility

Siena, 53100, Italy

Location

Unknown Facility

Udine, 33100, Italy

Location

Unknown Facility

Chihuahua City, 31000, Mexico

Location

Unknown Facility

Guadalajara, 44620, Mexico

Location

Unknown Facility

Guadalajara, 44690, Mexico

Location

Unknown Facility

Mexico City, 07760, Mexico

Location

Unknown Facility

Mexico City, 14080, Mexico

Location

Unknown Facility

San Luis Potosí City, 78240, Mexico

Location

Unknown Facility

Singapore, 119074, Singapore

Location

Unknown Facility

Singapore, 258499, Singapore

Location

Unknown Facility

Piešťany, 921 01, Slovakia

Location

Unknown Facility

Bern, 3010, Switzerland

Location

Unknown Facility

Lausanne, 1011, Switzerland

Location

Unknown Facility

Sankt Gallen, 9007, Switzerland

Location

Unknown Facility

Bangkok, 10400, Thailand

Location

Unknown Facility

Bangkok, 10700, Thailand

Location

Unknown Facility

Chiang Mai, 50200, Thailand

Location

Related Publications (4)

• Keystone EC, Anisfeld A, Ogale S, Devenport JN, Curtis JR. Continued benefit of tocilizumab plus disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis and inadequate clinical responses by week 8 of treatment. J Rheumatol. 2014 Feb;41(2):216-26. doi: 10.3899/jrheum.130489. Epub 2014 Jan 15.

  PMID: 24429164 DERIVED

• 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.

  PMID: 22491018 DERIVED

• Garnero P, Thompson E, Woodworth T, Smolen JS. Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum. 2010 Jan;62(1):33-43. doi: 10.1002/art.25053.

  PMID: 20039425 DERIVED

• Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R; OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008 Mar 22;371(9617):987-97. doi: 10.1016/S0140-6736(08)60453-5.

  PMID: 18358926 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 25, 2005
• First Posted: March 28, 2005
• Study Completion: October 1, 2007
• Last Updated: June 11, 2010

Record last verified: 2010-06

Locations

BR (2); AR (3); CH (3); IT (5); IL (6); AU (4); HU (3); ME (6); TH (3); CA (12); BU (3); FR (7); CN (2); DE (8); SG (2); SL (1)