Clinical trial NCT00996606: A Study of Tocilizumab in Combination With Disease-Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Moderate to Severe Active Rheumatoid Arthritis With an Inadequate Response to DMARDs
Official title: Open Label, Multicentric Phase IIIb Study to Evaluate the Effect of Tocilizumab in Combination With DMARDs in the Inhibition of Progression of Synovitis, Bone Marrow Edema, and Erosions Evaluated by Dedicated Magnetic Resonance Imaging (MRI) in the Hand of Patients With Rheumatoid Arthritis (RA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-10-16
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, single-arm study will evaluate the efficacy and safety of tocilizumab in combination with DMARDs in participants with moderate to severe active rheumatoid arthritis who have an inadequate response to DMARDs. Participants will receive tocilizumab as 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 4 weeks in addition to their current DMARD therapy.


Eligibility criteria: Inclusion Criteria:

* Moderate to severe active RA of ≥6 months duration
* DAS28 \>3.2
* Inadequate response to a stable dose of non-biologic DMARD for ≥2 months
* Those receiving oral corticosteroids must have been at stable dose for ≥25 days in the 28 days prior to first study treatment

Exclusion Criteria:

* Rheumatic autoimmune disease other than RA
* History of or current inflammatory joint disease other than RA
* Previous treatment with alkylating agents or total lymphoid irradiation
* Intra-articular or parenteral corticosteroids within 6 weeks prior to Baseline
* Previous treatment with any cell-depleting therapies
* American College of Rheumatology (ACR) Functional Class IV

Primary outcomes:
measure: Change From Baseline to Week 4 in Synovitis of the Wrist According to Rheumatoid Arthritis Magnetic Resonance Imaging (RAMRIS) Score
timeFrame: Baseline and Week 4
measure: Change From Baseline to Week 4 in Synovitis of the Wrist According to Relative Enhancement (RE) Before and After Contrast Injection
timeFrame: Baseline and Week 4
measure: Change From Baseline to Week 4 in Synovitis of the Wrist According to Rate of Early Enhancement (REE) Per Second Before and After Contrast Injection
timeFrame: Baseline and Week 4
Secondary outcomes:
measure: Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RAMRIS Score
timeFrame: Baseline and Weeks 2, 12, 24, 48
measure: Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to RE Before and After Contrast Injection
timeFrame: Baseline and Weeks 2, 12, 24, 48
measure: Change From Baseline to Weeks 2, 12, 24, and 48 in Synovitis of the Wrist According to REE Per Second Before and After Contrast Injection
timeFrame: Baseline and Weeks 2, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Synovitis of the Wrist and Metacarpo-Phalangeal (MCP) Joints According to Modified RAMRIS Score
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Erosion in the Wrist and MCP Joints
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erosion of the Wrist and MCP Joints According to RAMRIS Score
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Number of Bones With Bone Marrow Edema in the Wrist and MCP Joints
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Bone Marrow Edema of the Wrist and MCP Joints According to RAMRIS Score
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 24 and 48 in Total Modified Sharp Score (TMSS), Erosion Score (ES), and Joint Space Narrowing Score (JSNS)
timeFrame: Baseline and Weeks 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Ritchie Articular Index Score
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived Pain According to Visual Analog Scale (VAS) Score
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Perceived General Health According to VAS Score
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Disease Activity Score of 28 Joints (DAS28) Score
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Vascular Endothelial Growth Factor (VEGF) Concentration
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in High-Sensitivity C-Reactive Protein (hsCRP) Concentration
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Weeks 2 and 4 in Soluble Interleukin-6 Receptor (sIL6R) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Messenger Ribonucleic Acid (mRNA) for Interleukin (IL)-17 (2^Delta Cycle Threshold [ΔCt]) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in mRNA for IL-23 Receptor (2^ΔCt) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in mRNA for RAR-Related Orphan Receptor (ROR)-γT (2^ΔCt) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in mRNA for Forkhead Box Protein (FOXP) 3 (2^ΔCt) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Cluster of Differentiation (CD) 4-Positive Cells as a Percentage of Peripheral Blood Mononuclear Cells (PBMCs)
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD4 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD25-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD25 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD45 "RO" Isoform (RO)-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD45RO Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Cysteine-Cysteine Chemokine Receptor (CCR) 6-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CCR6 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CCR4-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CCR4 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in IL-23 Receptor p19 Subunit (IL-23Rp19)-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in IL-23Rp19 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Regulatory T (Treg) Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Treg Cells as a Percentage of T Cells
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Treg Cell Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Helper T (Th) 17 Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Th17 Cells as a Percentage of T Cells
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Th17 Cell Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD19-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD19 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD24-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD24 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD27-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD27 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD38-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in CD38 Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Immunoglobulin (Ig) M-Positive Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in IgM Mean Intensity of Fluorescence
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Mature B Cells as a Percentage of B Cells
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Week 4 in Mature B Cell Level
timeFrame: Baseline and Week 4
measure: Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Memory B Cells as a Percentage of B Cells
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Week 4 in Memory B Cell Level
timeFrame: Baseline and Week 4
measure: Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Transitional B Cells as a Percentage of B Cells
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Week 4 in Transitional B Cell Level
timeFrame: Baseline and Week 4
measure: Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of PBMCs
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Plasma B Cells as a Percentage of B Cells
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Week 4 in Plasma B Cell Level
timeFrame: Baseline and Week 4
measure: Change From Baseline to Weeks 2 and 4 in Th17 Cysteine-Cysteine Chemokine Ligand (CCL) 20 Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Th17CCL17 Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in B Cell-Attracting Chemokine (BCA) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Stromal Cell-Derived Factor (SDF) 1 Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in B Cell-Activating Factor (BAFF) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in A Proliferation-Inducing Ligand (APRIL) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Tumor Necrosis Factor (TNF)-α Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in IL-1β Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in IL-17 Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Monocyte Chemoattractant Protein (MCaP)-1 Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Osteocalcin Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Type I Collagen N-Propeptide Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in C-Terminal Telopeptide (CTX)-1 Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Type I Collagen C-Terminal Telopeptide (ICTP) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Type II Collagen N-Propeptide (PIIANP) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2 and 4 in Type II Collagen Helical Peptide (HELIX-II) Level
timeFrame: Baseline and Weeks 2, 4
measure: Change From Baseline to Weeks 2, 4, 12, 24, and 48 in Hemoglobin (Hb) Concentration
timeFrame: Baseline and Weeks 2, 4, 12, 24, 48
measure: Change From Baseline to Day 2 and Weeks 2 and 4 in Soluble Transferrin Receptor (STR) Concentration
timeFrame: Baseline; Day 2; and Weeks 2, 4
measure: Change From Baseline to Week 48 in Initial Rate of Enhancement (IRE) by DYNAMIKA Software Analysis
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Maximum Enhancement (ME) by DYNAMIKA Software Analysis
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Number of Enhancing Voxels (Ntotal) by DYNAMIKA Software Analysis
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Number of Persistent Enhancing Voxels (Npersistent) by DYNAMIKA Software Analysis
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Number of Plateau Enhancing Voxels (Nplateau) by DYNAMIKA Software Analysis
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Number of Washout Enhancing Voxels (Nwashout) by DYNAMIKA Software Analysis
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Ntotal×IRE by DYNAMIKA Software Analysis
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Ntotal×ME by DYNAMIKA Software Analysis
timeFrame: Baseline and Week 48
Other outcomes:
Locations:
city: Coppito
country: Italy
state: Abruzzo
city: Napoli
country: Italy
state: Campania
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
state: Liguria
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Pavia
country: Italy
state: Lombardia
city: Palermo
country: Italy
state: Sicilia
city: Pisa
country: Italy
state: Toscana
city: Cona (Ferrara)
country: Italy
state: Veneto
city: Padova
country: Italy
state: Veneto
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: