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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01007435




Registration number
NCT01007435
Ethics application status
Date submitted
3/11/2009
Date registered
4/11/2009
Date last updated
26/07/2017

Titles & IDs
Public title
A Study of Tocilizumab as Monotherapy and in Combination With Methotrexate Versus Methotrexate in Patients With Early Moderate to Severe Rheumatoid Arthritis
Scientific title
A Multi-center, Randomized, Double-blind, Parallel Group Study of the Safety, Disease Remission and Prevention of Structural Joint Damage During Treatment With Tocilizumab (TCZ), as a Monotherapy and in Combination With Methotrexate (MTX), Versus Methotrexate in Patients With Early, Moderate to Severe Rheumatoid Arthritis
Secondary ID [1] 0 0
2009-012759-12
Secondary ID [2] 0 0
WA19926
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
Treatment: Drugs - Placebo to tocilizumab
Treatment: Drugs - Methotrexate
Treatment: Drugs - Placebo to methotrexate

Experimental: (A) Tocilizumab 8 mg/kg + placebo to methotrexate - Patients received tocilizumab 8 mg/kg iv every 4 weeks + placebo to methotrexate orally once a week for 104 weeks.

Experimental: (B) Tocilizumab 8 mg/kg + methotrexate - Patients received tocilizumab 8 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.

Experimental: (C) Tocilizumab 4 mg/kg + methotrexate - Patients received tocilizumab 4 mg/kg iv every 4 weeks + methotrexate orally once a week for 104 weeks.

Active comparator: (D) Placebo to tocilizumab + methotrexate - Patients received placebo tocilizumab intravenously (iv) every 4 weeks + methotrexate orally once a week for 104 weeks.


Treatment: Drugs: Tocilizumab
Tocilizumab was supplied in vials.

Treatment: Drugs: Placebo to tocilizumab
Placebo to tocilizumab was supplied in vials.

Treatment: Drugs: Methotrexate
Initially, patients received methotrexate 7.5 mg (3, 2.5 mg tablets) orally once a week. If a patient had swollen or tender joints, the dose was increased to 15 mg and 20 mg weekly, at the Week 4 and Week 8 visits, respectively.

Treatment: Drugs: Placebo to methotrexate
Patients received placebo to methotrexate orally once a week.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 24
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Percentage of Participants With a Disease Activity Score 28 (DAS28) Remission Response at Week 52
Timepoint [1] 0 0
Week 52
Secondary outcome [2] 0 0
Percentage of Patients With an Improvement = 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Weeks 24 and 52
Timepoint [2] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [3] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52
Timepoint [3] 0 0
Baseline to Week 52
Secondary outcome [4] 0 0
Change From Baseline in Modified Sharp Erosion Score at Week 52
Timepoint [4] 0 0
Baseline to Week 52
Secondary outcome [5] 0 0
Change From Baseline in Sharp Joint Space Narrowing Score at Week 52
Timepoint [5] 0 0
Baseline to Week 52
Secondary outcome [6] 0 0
Percentage of Participants With a Major Clinical Response at Week 52
Timepoint [6] 0 0
Baseline to Week 52
Secondary outcome [7] 0 0
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 24 and 52
Timepoint [7] 0 0
Baseline to Weeks 24 and 52
Secondary outcome [8] 0 0
Change From Baseline in Short Form 36 (SF-36) Physical Component Summary (PCS) Scores at Weeks 24 and 52
Timepoint [8] 0 0
Baseline to Weeks 24 and 52

Eligibility
Key inclusion criteria
* Adult patients = 18 years of age.
* Rheumatoid arthritis of = 2 years duration.
* Disease Activity Score 28 (DAS28) > 3.2.
* Swollen joint count (SJC) = 4 of 66 joints, tender joint count (TJC) = 6 of 68 joints.
* Rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) positive (if RF and anti-CCP negative > 1 erosion required at screening).
* Erythrocyte sedimentation rate (ESR) = 28 mm/h or C-reactive protein (CRP) = 10 mg/L at screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous treatment with tocilizumab.
* Previous treatment with methotrexate or biologic agent.
* Rheumatic autoimmune disease other than rheumatoid arthritis (RA).
* History of or current inflammatory joint disease other than RA.
* Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in RA.

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 3
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
31/10/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/01/2014
Sample size
Target
Accrual to date
Final
1162
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital; Rheumatology - Camperdown
Recruitment hospital [2] 0 0
Sunshine Coast Rheumatology Research Unit - Maroochydore
Recruitment hospital [3] 0 0
Queen Elizabeth Hospital; Rheumatology - Woodville
Recruitment hospital [4] 0 0
Menzies Research Institute - Hobart
Recruitment hospital [5] 0 0
Cabrini Medical Centre; Rheumatology - Malvern
Recruitment hospital [6] 0 0
Worthing Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4558 - Maroochydore
Recruitment postcode(s) [3] 0 0
5011 - Woodville
Recruitment postcode(s) [4] 0 0
7100 - Hobart
Recruitment postcode(s) [5] 0 0
3144 - Malvern
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, double-blind, parallel group study will assess the safety, disease remission, and prevention of structural joint damage in patients with early moderate to severe rheumatoid arthritis treated with tocilizumab as monotherapy or in combination with methotrexate, versus methotrexate alone. Patients will be randomized to receive either (A) tocilizumab (8 mg/kg iv every 4 weeks) plus placebo, (B) tocilizumab (8 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), (C) tocilizumab (4 mg/kg iv every 4 weeks) plus methotrexate (7.5-20 mg po weekly), or (D) placebo plus methotrexate (7.5-20 mg po weekly). Patients in groups C and D who have not achieved low disease activity at week 52 can receive tocilizumab 8 mg/kg iv every 4 weeks. Anticipated time on study treatment is 104 weeks.
Trial website
https://clinicaltrials.gov/study/NCT01007435
Trial related presentations / publications
Burmester GR, Rigby WF, van Vollenhoven RF, Kay J, Rubbert-Roth A, Blanco R, Kadva A, Dimonaco S. Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial. Ann Rheum Dis. 2017 Jul;76(7):1279-1284. doi: 10.1136/annrheumdis-2016-210561. Epub 2017 Apr 7.
Burmester GR, Rigby WF, van Vollenhoven RF, Kay J, Rubbert-Roth A, Kelman A, Dimonaco S, Mitchell N. Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial. Ann Rheum Dis. 2016 Jun;75(6):1081-91. doi: 10.1136/annrheumdis-2015-207628. Epub 2015 Oct 28.
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/NCT01007435