Clinical trial NCT01661140: A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Severe Active Rheumatoid Arthritis, Comparing Tapering Versus Maintaining the Methotrexate Dosage
Official title: Randomized, Phase IV, Placebo-controlled, Comparative Study to Evaluate the Efficacy and Safety of Tapering Methotrexate (MTX) Dosage Versus Maintaining the Dosage in Patients With Severe Active Rheumatoid Arthritis (RA) Who Have Demonstrated an Inadequate Response (IR) to Prior Disease-modifying Anti-rheumatic Drugs (DMARDs) Treatment and Have Initiated RoActemra (RoActemra, TCZ) in Combination With MTX
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-08-09
Enrollment: 427
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 randomized, placebo-controlled, double-blind study will compare the safety and efficacy of tapering methotrexate (MTX) versus maintaining MTX dosage in patients with severe active rheumatoid arthritis and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) initiated on treatment with tocilizumab. Participants will receive tocilizumab 8 mg/kg intravenously every 4 weeks and MTX orally weekly throughout the study. At Week 24, participants achieving a good/moderate EULAR response will be randomized receiving the MTX Tapering arm or MTX Maintenance arm. Up to Week 56 participants will receive either tapering or stable dose MTX in combination with tocilizumab. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.


Eligibility criteria: Inclusion Criteria:

* Adult patients, \>/= 18 years of age
* Active severe rheumatoid arthritis (DAS28 \> 5.1) according to European League of Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria
* Inadequate response to a trial of 2 DMARDs, including methotrexate, a trial being defined as 6 months with 2 months at standard dose; no previous treatment with a biologic agent such as a tumor necrosis factor (TNF) inhibitor
* Oral corticosteroids must have been at a stable dose of \</= 10 mg/day prednisolone or equivalent for at least 25 out of 28 days prior to start of treatment (Day 1)

Exclusion Criteria:

* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
* Rheumatic autoimmune disease other than rheumatoid arthritis
* Functional class IV as defined by the ACR Classification of Functional Status in RA
* Prior history of or current inflammatory joint disease other than RA
* Previous treatment with tocilizumab
* Previous treatment with any biologic drug (e.g. TNF inhibitor) that is used in the treatment of RA
* Intraarticular or parenteral corticosteroids within 6 weeks prior to enrollment
* Inadequate liver, bone marrow or hepatic function
* Positive for hepatitis B, hepatitis C or HIV infection
* Pregnant or breastfeeding women
* Females of child-bearing potential who are not using reliable means of contraception
* History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
* Active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections
* History of, or currently active, primary or secondary immunodeficiency

Primary outcomes:
measure: Percentage of Participants Maintaining Previous Disease Activity (European League Against Rheumatism [EULAR] Response) From Week 24 (Time of Randomization) to Week 60
timeFrame: From randomization to Week 60
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 60
timeFrame: Randomization (Week 24), Week 60
measure: Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 72
timeFrame: Randomization (Week 24), Week 72
measure: Percentage of Participants Who Achieve Score of <=1 in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 60 and 72
timeFrame: Week 60, 72
measure: Percentage of Participants Who Achieve a Disease Activity Score In 28 Joints (DAS28) <= 3.2
timeFrame: Week 60, 72
measure: Percentage of Participants Who Achieve DAS28 Remission (DAS28 < 2.6)
timeFrame: Week 60, 72
measure: Percentage of Participants Who Achieve Change in Disease Activity Score (cDAS) >=1.2
timeFrame: Week 60, 72
measure: Percentage of Participants Who Achieve Clinical Disease Activity Index (CDAI) Remission (CDAI < 2.8) at Week 60 and 72
timeFrame: Randomization (Week 24), Week 60, 72
measure: Percentage of Participants Who Achieve Simplified Disease Activity Index (SDAI) Remission (SDAI < 3.3) at Week 60 and 72
timeFrame: Randomization (Week 24), Week 60, 72
measure: Percentage of Participants With Improvement in Physical Function Using Health Assessment Questionnaire [HAQ] at Week 60 and 72
timeFrame: Randomization (Week 24), Week 60, 72
measure: Percentage of Participants With Improvement in Physical Function Using Functional Assessment of Chronic Illness Therapy - Fatigue [FACIT-F] at Week 60 and 72
timeFrame: Randomization (Week 24), Week 60, 72
measure: Percentage of Participants With Improvement in Physical Function Using 12-item Short Form Health Survey [SF-12]) at Week 60 and 72
timeFrame: Randomization (Week 24), Week 60, 72
measure: Percentage of Participants With Anemia
timeFrame: Week 0 up to Week 72
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Week 0 up to Week 72
measure: Percentage of Participants Able to Discontinue Methotrexate
timeFrame: Week 0 up to Week 60
measure: Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP)
timeFrame: Randomization (Week 24), Week 60, 72
measure: Hours Actually Worked and Work Hours Missed Assessed Using the WPAI-SHP
timeFrame: Randomization (Week 24), Week 60, Week 72
measure: Change in Productivity and Regular Daily Activities Affected by Rheumatoid Arthritis Assessed Using the WPAI-SHP
timeFrame: Randomization (Week 24), Week 60, 72
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
city: Abergavenny
country: United Kingdom
city: Ashford
country: United Kingdom
city: Aylesbury
country: United Kingdom
city: Barnsley
country: United Kingdom
city: Basingstoke
country: United Kingdom
city: Bournemouth
country: United Kingdom
city: Brighton
country: United Kingdom
city: Bury St Edmonds
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Cannock
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Chelmsford
country: United Kingdom
city: Chester
country: United Kingdom
city: Coventry
country: United Kingdom
city: Crewe
country: United Kingdom
city: Darlington
country: United Kingdom
city: Derby
country: United Kingdom
city: Dudley
country: United Kingdom
city: Dundee
country: United Kingdom
city: Eastbourne
country: United Kingdom
city: Exeter
country: United Kingdom
city: Gillingham
country: United Kingdom
city: Greenock
country: United Kingdom
city: Guildford
country: United Kingdom
city: Harrogate
country: United Kingdom
city: Hull
country: United Kingdom
city: Isle of Wight
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: Llantrisant
country: United Kingdom
city: Londonderry
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Maidstone
country: United Kingdom
city: Manchester
country: United Kingdom
city: Manchester
country: United Kingdom
city: Middlesborough
country: United Kingdom
city: North Shields
country: United Kingdom
city: Northampton
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Oldham
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Reading
country: United Kingdom
city: Salford
country: United Kingdom
city: Salisbury
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Somerset
country: United Kingdom
city: Southampton
country: United Kingdom
city: Southport
country: United Kingdom
city: Stevenage
country: United Kingdom
city: Stoke-on-trent
country: United Kingdom
city: Sunderland
country: United Kingdom
city: Sutton in Ashfield
country: United Kingdom
city: Swindon
country: United Kingdom
city: Torquay
country: United Kingdom
city: Truro
country: United Kingdom
city: Walsall
country: United Kingdom
city: Warwick
country: United Kingdom
city: Westcliffe-on-sea
country: United Kingdom
city: Wirral
country: United Kingdom
city: Wolverhampton
country: United Kingdom
city: Worthing
country: United Kingdom
city: Wrightington
country: United Kingdom
city: York
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: