A Study of Tocilizumab (RoActemra/Actemra) Versus Adalimumab in Patients With Rheumatoid Arthritis

NCT01119859 | Completed Phase 4 Results

• 2 other identifiers: WA199242009-015845-21
• Study Type: interventional
• Target: 326
• Locations: 15 countries
• Sites: 82

Brief Summary

This randomized, blinded, parallel arm study evaluated the efficacy and safety of tocilizumab (RoActemra/Actemra) versus adalimumab as monotherapy in patients with rheumatoid arthritis who are intolerant of methotrexate or where continued treatment with methotrexate was considered inappropriate. Patients were randomized to receive either tocilizumab 8 mg/kg intravenously (iv) every 4 weeks plus placebo subcutaneously (sc) every 2 weeks, or adalimumab 40 mg sc every 2 weeks plus placebo iv every 4 weeks. Treatment was anticipated to last 24 weeks. With regard to the blind, the study nurse was unblinded due to the nature of the treatment administration, but the investigator and the patient remained blinded.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 24 in the Disease Activity Score 28 (DAS28)

  The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. The analysis was adjusted for stratification factors of duration of RA (≤ 2 years and \> 2 years) and region (US and non-US).

  Baseline to Week 24

Secondary Outcomes (5)

• Percentage of Patients With a Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Week 24

  Week 24

• Percentage of Patients With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Week 24

  Week 24

• Percentage of Patients With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Week 24

  Baseline to Week 24

• Percentage of Patients With a European League Against Rheumatism (EULAR) Good Response at Week 24

  Baseline to Week 24

• Percentage of Patients With a European League Against Rheumatism (EULAR) Good or Moderate Response at Week 24

  Baseline to Week 24

Study Arms (2)

Tocilizumab 8 mg/kg

EXPERIMENTAL

Patients received 6 infusions of tocilizumab 8 mg/kg intravenously every 4 weeks and 12 injections of placebo to adalimumab subcutaneously every 2 weeks.

Drug: Tocilizumab; Drug: Placebo to adalimumab

Adalimumab 40 mg

ACTIVE COMPARATOR

Patients received 12 injections of adalimumab 40 mg subcutaneously every 2 weeks and 6 infusions of placebo to tocilizumab intravenously every 4 weeks.

Drug: Adalimumab; Drug: Placebo to tocilizumab

Interventions

Tocilizumab DRUG

The maximum dose was 800 mg for patients weighing more than 100 kg. Tocilizumab was infused into an arm vein over a 1-hour period.

Also known as: RoActemra, Actemra

Tocilizumab 8 mg/kg

Adalimumab DRUG

Adalimumab 40 mg

Placebo to tocilizumab DRUG

Adalimumab 40 mg

Placebo to adalimumab DRUG

Tocilizumab 8 mg/kg

Eligibility Criteria

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

You may qualify if:

• Adult patients, ≥ 18 years of age.
• Rheumatoid arthritis of \> 6 months duration.
• Intolerant of methotrexate or continued treatment with methotrexate is considered inappropriate.
• All disease-modifying anti-rheumatic drugs (DMARD) are to be withdrawn prior to receiving study drug.
• Weight ≤ 150 kg.

You may not qualify if:

• Major surgery (including joint surgery) within 12 weeks prior to baseline or planned major surgery within 6 months after baseline.
• History of or current inflammatory joint disease other than rheumatoid arthritis (RA).
• Treatment with a biologic agent at any time prior to baseline.
• Intra-articular or parenteral corticosteroids ≤ 4 weeks prior to baseline.
• Active current infection or history of recurrent bacterial, viral, fungal or mycobacterial infection.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (82)

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Anniston, Alabama, 36207, United States

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Birmingham, Alabama, 35294, United States

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Scottsdale, Arizona, 85258, United States

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Hot Springs, Arkansas, 71913, United States

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Little Rock, Arkansas, 72205, United States

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San Diego, California, 92108, United States

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Colorado Springs, Colorado, 80910, United States

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Trumbull, Connecticut, 06611, United States

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Boca Raton, Florida, 33486, United States

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Fort Lauderdale, Florida, 33334, United States

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Ormond Beach, Florida, 32174, United States

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Idaho Falls, Idaho, 83404, United States

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Springfield, Illinois, 62704, United States

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Cumberland, Maryland, 21502, United States

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Flowood, Mississippi, 39232, United States

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Tupelo, Mississippi, 38802, United States

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Lincoln, Nebraska, 68516, United States

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Dover, New Hampshire, 03820, United States

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New Brunswick, New Jersey, 08903, United States

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Hickory, North Carolina, 28601, United States

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Dayton, Ohio, 45402, United States

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Duncansville, Pennsylvania, 16635, United States

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Willow Grove, Pennsylvania, 19090, United States

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Wyomissing, Pennsylvania, 19610, United States

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Greenville, South Carolina, 29601, United States

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Hixson, Tennessee, 37343, United States

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Houston, Texas, 77074, United States

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Lubbock, Texas, 79424, United States

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Mesquite, Texas, 75150, United States

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Nassau Bay, Texas, 77058, United States

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Waco, Texas, 76708, United States

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Spokane, Washington, 99204, United States

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Tacoma, Washington, 98405, United States

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Maroochydore, 4558, Australia

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Sydney, 2050, Australia

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Brussels, 1070, Belgium

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Liège, 4000, Belgium

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Curitiba, 80060-240, Brazil

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Goiânia, 74110010, Brazil

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São Paulo, 04266-010, Brazil

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Prague, 12850, Czechia

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Helsinki, 00290, Finland

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Jyväskylä, 40100, Finland

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Baden-Baden, 76530, Germany

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Berlin, 14059, Germany

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Cologne, 50924, Germany

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Essen, 45239, Germany

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Heidelberg, 69120, Germany

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Herne, 44652, Germany

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Hildesheim, 31134, Germany

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Osnabrück, 49074, Germany

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Ratingen, 40882, Germany

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Würzburg, 97080, Germany

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Athens, 11527, Greece

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Heraklion, 71110, Greece

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Thessaloniki, 54642, Greece

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Mexicali, 21100, Mexico

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Mexico City, 11850, Mexico

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Obregón, 85000, Mexico

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Almada, 2801-951, Portugal

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Lisbon, 1649-035, Portugal

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Porto, 4200-319, Portugal

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A Coruña, 15006, Spain

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Barcelona, 08036, Spain

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Madrid, 28006, Spain

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Santiago de Compostela, 15705, Spain

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Seville, 41009, Spain

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Stockholm, 17176, Sweden

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Uppsala, 751 85, Sweden

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Aarau, 5000, Switzerland

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Geneva, 1211, Switzerland

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Lausanne, 1011, Switzerland

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Sankt Gallen, 9007, Switzerland

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Zurich, 8091, Switzerland

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Ankara, 06100, Turkey (Türkiye)

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Antalya, 07059, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Cannock, WS11 5XY, United Kingdom

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Leeds, LS7 4SA, United Kingdom

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London, E11 1NR, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Poole, BH15 2JB, United Kingdom

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Related Publications (4)

• 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.

  PMID: 28955499 DERIVED

• Gabay C, McInnes IB, Kavanaugh A, Tuckwell K, Klearman M, Pulley J, Sattar N. Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis. Ann Rheum Dis. 2016 Oct;75(10):1806-12. doi: 10.1136/annrheumdis-2015-207872. Epub 2015 Nov 27.

  PMID: 26613768 DERIVED

• Dennis G Jr, Holweg CT, Kummerfeld SK, Choy DF, Setiadi AF, Hackney JA, Haverty PM, Gilbert H, Lin WY, Diehl L, Fischer S, Song A, Musselman D, Klearman M, Gabay C, Kavanaugh A, Endres J, Fox DA, Martin F, Townsend MJ. Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res Ther. 2014;16(2):R90. doi: 10.1186/ar4555. Epub 2014 Apr 30.

  PMID: 25167216 DERIVED

• Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, Klearman M, Musselman D, Agarwal S, Green J, Kavanaugh A; ADACTA Study Investigators. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013 May 4;381(9877):1541-50. doi: 10.1016/S0140-6736(13)60250-0. Epub 2013 Mar 18.

  PMID: 23515142 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Adalimumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2010
• First Posted: May 10, 2010
• Study Start: May 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: February 11, 2013
• Results First Posted: February 11, 2013

Record last verified: 2013-01

Locations

CZ (1); ME (3); FI (2); TU (3); BE (2); US (33); PT (3); BR (3); ES (5); AU (2); CH (5); GR (3); DE (10); SE (2); GB (5)