Clinical trial NCT01034397: A Study of Tocilizumab Plus Non-biological DMARD in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to Non-biological DMARDs
Official title: A Randomized, Double-blind, Placebo-controlled Study to Assess Efficacy of Tocilizumab+Non-biological DMARD in Reducing Synovitis as Measured by MRI at 12 Weeks After Initiation of Treatment in Patients With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Non-biological DMARDs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-12-17
Enrollment: 54
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, double-blind, placebo-controlled study will use Magnetic Resonance Imaging (MRI) to assess the efficacy of tocilizumab plus non-biological DMARD in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to non-biological DMARDS. Patients will be randomized to receive either intravenous tocilizumab at 8mg/kg (minimal dose 480mg, maximum dose 800mg) or placebo every 4 weeks, in addition to their stable dose of non-biological DMARD. Anticipated time on study treatment is 24 weeks, and target sample size is \<100.


Eligibility criteria: Inclusion Criteria:

* adult patients, \>/=18 years of age
* moderate to severe rheumatoid arthritis of \>/=6 months duration
* synovitis (swollen and tender joint) in the wrist of the dominant hand
* non-biologic DMARDs at stable dose for \>/=12 weeks prior to baseline
* oral corticosteroids at stable dose for at least 25 out of 28 days prior to baseline

Exclusion Criteria:

* rheumatic autoimmune disease other than RA
* history of or current inflammatory joint disease other than RA
* functional class IV (ACR classification)
* intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
* previous treatment with a biologic agent for RA

Primary outcomes:
measure: Percent Change From Baseline to Week 12 in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score
timeFrame: Week 12
Secondary outcomes:
measure: Percent Change From Baseline to Week 12 in OMERACT RAMRIS Score
timeFrame: Week 12
measure: Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Score
timeFrame: Week 12
measure: Percent Change From Baseline to Week 24 in OMERACT RAMRIS Score
timeFrame: Week 24
measure: Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Score
timeFrame: Week 24
measure: Absolute Change From Baseline to Week 12 in OMERACT-RAMRIS Synovitis Score
timeFrame: Week 12
measure: Absolute Change From Baseline to Week 24 in OMERACT-RAMRIS Synovitis Score
timeFrame: Week 24
measure: Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score
timeFrame: Week 12
measure: Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score
timeFrame: Week 12
measure: Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score
timeFrame: Week 24
measure: Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score
timeFrame: Week 24
measure: Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score
timeFrame: Week 12
measure: Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score
timeFrame: Week 12
measure: Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score
timeFrame: Week 24
measure: Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score
timeFrame: Week 24
measure: Percent Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score
timeFrame: Week 12
measure: Absolute Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score
timeFrame: Week 12
measure: Percent Change From Baseline to Week 24 in DCE-MRI EER Global Score
timeFrame: Week 24
measure: Absolute Change From Baseline to Week 24 in DCE-MRI EER Global Score
timeFrame: Week 24
measure: Percent Change From Baseline to Week 12 in DCE-MRI EER MCP Score
timeFrame: Week 12
measure: Absolute Change From Baseline to Week 12 in DCE-MRI EER MCP Score
timeFrame: Week 12
measure: Percent Change From Baseline to Week 24 in DCE-MRI EER MCP Score
timeFrame: Week 24
measure: Absolute Change From Baseline to Week 24 in DCE-MRI EER MCP Score
timeFrame: Week 24
measure: Percent Change From Baseline to Week 12 in DCE-MRI EER Wrist Score
timeFrame: Week 12
measure: Absolute Change From Baseline to Week 12 in DCE-MRI EER Wrist Score
timeFrame: Week 12
measure: Percent Change From Baseline to Week 24 in DCE-MRI EER Wrist Score
timeFrame: Week 24
measure: Absolute Change From Baseline to Week 24 in DCE-MRI EER Wrist Score
timeFrame: Week 24
measure: Disease Activity Score Based on 28-Joint Count (DAS28)
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline to Week 12 in DAS28 Global Score
timeFrame: Week 12
measure: Change From Baseline to Week 24 in DAS28 Global Score
timeFrame: Week 24
measure: Tender and Swollen Joint Counts
timeFrame: Weeks 12 and 24
measure: Change From Baseline to Week 12 in TJC
timeFrame: Week 12
measure: Change From Baseline to Week 24 in TJC
timeFrame: Week 24
measure: Change From Baseline to Week 12 in SJC
timeFrame: Week 12
measure: Change From Baseline to Week 24 in SJC
timeFrame: Week 24
measure: Change From Baseline to Week 12 in Patient Global Assessment of Disease Activity
timeFrame: Week 12
measure: Change From Baseline to Week 24 in Patient Global Assessment of Disease Activity
timeFrame: Week 24
measure: Patient Global Assessment of Pain
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline to Week 12 in Patient Global Assessment of Pain
timeFrame: Week 12
measure: Change From Baseline to Week 24 in Patient Global Assessment of Pain
timeFrame: Week 24
measure: Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline to Week 12 in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Week 12
measure: Change From Baseline to Week 24 in ESR
timeFrame: Week 24
measure: Change From Baseline to Week 12 in C-Reactive Protein (CRP)
timeFrame: Week 12
measure: Change From Baseline to Week 24 in CRP
timeFrame: Week 24
measure: Change From Baseline to Week 12 in Serum Cortisol
timeFrame: Week 12
measure: Change From Baseline to Week 24 in Serum Cortisol
timeFrame: Week 24
measure: Change From Baseline to Week 12 in Plasma Adrenocorticotrophic Hormone (ACTH)
timeFrame: Week 12
measure: Change From Baseline to Week 24 in Plasma ACTH
timeFrame: Week 24
measure: Change From Baseline to Week 12 in Serum Androstenedione
timeFrame: Week 12
measure: Change From Baseline to Week 12 in 17 Hydroxy Progesterone (17OHP)
timeFrame: Week 12
measure: Change From Baseline to Week 24 in Serum Androstenedione
timeFrame: Week 24
measure: Change From Baseline to Week 24 in 17OHP
timeFrame: Week 24
measure: Change From Baseline to Week 12 in Serum Dehydroepiandrosterone (DHEA)
timeFrame: Week 12
measure: Change From Baseline to Week 24 in Serum DHEA
timeFrame: Week 24
measure: Change From Baseline to Week 12 in Neuropeptide Y
timeFrame: Week 12
measure: Change From Baseline to Week 24 in Neuropeptide Y
timeFrame: Week 24
Other outcomes:
Locations:
city: Almada
country: Portugal
city: Coimbra
country: Portugal
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Ponte Do Lima
country: Portugal
city: Porto
country: Portugal
city: Porto
country: Portugal
city: Vila Nova de Gaia
country: Portugal
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: