Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01119859




Registration number
NCT01119859
Ethics application status
Date submitted
1/04/2010
Date registered
10/05/2010
Date last updated
11/02/2013

Titles & IDs
Public title
A Study of Tocilizumab (RoActemra/Actemra) Versus Adalimumab in Patients With Rheumatoid Arthritis
Scientific title
A Multi-center, Randomized, Blinded, Parallel-group Study of the Reduction of Signs and Symptoms During Monotherapy Treatment With Tocilizumab 8 mg/kg Intravenously Versus Adalimumab 40 mg Subcutaneously in Patients With Rheumatoid Arthritis
Secondary ID [1] 0 0
2009-015845-21
Secondary ID [2] 0 0
WA19924
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tocilizumab

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

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


Treatment: Drugs: Tocilizumab
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 24 in the Disease Activity Score 28 (DAS28)
Timepoint [1] 0 0
Baseline to Week 24
Secondary outcome [1] 0 0
Percentage of Patients With a Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Percentage of Patients With Low Disease Activity (Disease Activity Score 28 [DAS28] = 3.2) at Week 24
Timepoint [2] 0 0
Week 24
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline to Week 24
Secondary outcome [4] 0 0
Percentage of Patients With a European League Against Rheumatism (EULAR) Good Response at Week 24
Timepoint [4] 0 0
Baseline to Week 24
Secondary outcome [5] 0 0
Percentage of Patients With a European League Against Rheumatism (EULAR) Good or Moderate Response at Week 24
Timepoint [5] 0 0
Baseline to Week 24

Eligibility
Key inclusion criteria
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2012
Sample size
Target
Accrual to date
Final
326
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Maroochydore
Recruitment hospital [2] 0 0
- Sydney
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Idaho
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Mississippi
Country [12] 0 0
United States of America
State/province [12] 0 0
Nebraska
Country [13] 0 0
United States of America
State/province [13] 0 0
New Hampshire
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
Belgium
State/province [22] 0 0
Bruxelles
Country [23] 0 0
Belgium
State/province [23] 0 0
Liege
Country [24] 0 0
Brazil
State/province [24] 0 0
Curitiba
Country [25] 0 0
Brazil
State/province [25] 0 0
Goiania
Country [26] 0 0
Brazil
State/province [26] 0 0
Sao Paulo
Country [27] 0 0
Czech Republic
State/province [27] 0 0
Prague
Country [28] 0 0
Finland
State/province [28] 0 0
Helsinki
Country [29] 0 0
Finland
State/province [29] 0 0
Jyväskylä
Country [30] 0 0
Germany
State/province [30] 0 0
Baden-baden
Country [31] 0 0
Germany
State/province [31] 0 0
Berlin
Country [32] 0 0
Germany
State/province [32] 0 0
Essen
Country [33] 0 0
Germany
State/province [33] 0 0
Heidelberg
Country [34] 0 0
Germany
State/province [34] 0 0
Herne
Country [35] 0 0
Germany
State/province [35] 0 0
Hildesheim
Country [36] 0 0
Germany
State/province [36] 0 0
Köln
Country [37] 0 0
Germany
State/province [37] 0 0
Osnabrück
Country [38] 0 0
Germany
State/province [38] 0 0
Ratingen
Country [39] 0 0
Germany
State/province [39] 0 0
Würzburg
Country [40] 0 0
Greece
State/province [40] 0 0
Athens
Country [41] 0 0
Greece
State/province [41] 0 0
Heraklion
Country [42] 0 0
Greece
State/province [42] 0 0
Thessaloniki
Country [43] 0 0
Mexico
State/province [43] 0 0
Mexicali
Country [44] 0 0
Mexico
State/province [44] 0 0
Mexico, Df
Country [45] 0 0
Mexico
State/province [45] 0 0
Obregon
Country [46] 0 0
Portugal
State/province [46] 0 0
Almada
Country [47] 0 0
Portugal
State/province [47] 0 0
Lisboa
Country [48] 0 0
Portugal
State/province [48] 0 0
Porto
Country [49] 0 0
Spain
State/province [49] 0 0
Barcelona
Country [50] 0 0
Spain
State/province [50] 0 0
La Coruna
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Santiago de Compostela
Country [53] 0 0
Spain
State/province [53] 0 0
Sevilla
Country [54] 0 0
Sweden
State/province [54] 0 0
Stockholm
Country [55] 0 0
Sweden
State/province [55] 0 0
Uppsala
Country [56] 0 0
Switzerland
State/province [56] 0 0
Aarau
Country [57] 0 0
Switzerland
State/province [57] 0 0
Genève
Country [58] 0 0
Switzerland
State/province [58] 0 0
Lausanne
Country [59] 0 0
Switzerland
State/province [59] 0 0
St. Gallen
Country [60] 0 0
Switzerland
State/province [60] 0 0
Zürich
Country [61] 0 0
Turkey
State/province [61] 0 0
Ankara
Country [62] 0 0
Turkey
State/province [62] 0 0
Antalya
Country [63] 0 0
Turkey
State/province [63] 0 0
Istanbul
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Cannock
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Leeds
Country [66] 0 0
United Kingdom
State/province [66] 0 0
London
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Newcastle Upon Tyne
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Poole

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01119859
Trial related presentations / publications
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.
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.
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.
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. Erratum In: Lancet. 2013 Dec 7;382(9908):1878. Lancet. 2013 May 4;381(9877):1540. Dosage error in article text.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01119859