A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs.
- Conditions
- Rheumatoid Arthritis
- Interventions
- Drug: tocilizumab [RoActemra/Actemra]Drug: DMARDs (disease-modifying antirheumatic drugs)
- Registration Number
- NCT00996203
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This open-label single arm study will evaluate the efficacy and safety of tocilizumab added to traditional disease-modifying antirheumatic drugs (DMARDs) in patients with moderate to severe active rheumatoid arthritis and an inadequate response to DMARDs. Patients will receive tocilizumab 8 mg/kg by intravenous infusion every 4 weeks for 24 weeks, in addition to their current non-biologic DMARDs at stable doses. Anticipated time on study treatment is 24 weeks, and the target sample size is 200.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 201
- adult patients, >/= 18 years of age
- moderate to severe active rheumatoid arthritis of >/=6 months duration
- inadequate clinical response to current non-biologic DMARDs
- current DMARDs must be at stable dose for 8 weeks prior to study entry
- oral corticosteroids (</=10mg/day prednisone or equivalent) and NSAIDs must be at stable dose for >/=4 weeks prior to screening
- rheumatic autoimmune disease other than RA
- history of or current inflammatory joint disease other than RA
- previous treatment with any biologic DMARD
- functional class IV as defined by the ACR classification
- intra-articular or parenteral corticosteroids within 6 weeks prior to screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 tocilizumab [RoActemra/Actemra] - 1 DMARDs (disease-modifying antirheumatic drugs) -
- Primary Outcome Measures
Name Time Method Health Assessment Questionnaire (HAQ) Score Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. Withdrawal Visit is the final visit prior to the withdrawal of the subject from the study.
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment Weeks 4, 8, 12, 16, 20, and 24 HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
Change in HAQ Score at Week 24 Baseline and Week 24 HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
- Secondary Outcome Measures
Name Time Method Erythrocyte Sedimentation Rate Weeks 4, 8, 12, 16, 20, and 24 ESR (mm/hr) is used to determine the acute phase response.
Pain Score as Assessed by Visual Analogue Scale (VAS) Weeks 0, 4, 8, 12, 16, 20, and 24 Participant's global assessment of pain was assessed using a 100-millimeter (mm) horizontal VAS (0 to 100 mm) with 0=pain absent and 100=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain.
Change in EQ-5D Score at Week 24 From Baseline Baseline and Week 24 EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression. Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Minimum clinically significant change in EQ-5D corresponds to the parameter differences before and after treatment = 0.10. Graduations of assessment of the therapy efficacy by EQ-5D are: Difference (Δ) EQ-5D less than (\<)0.10 points: none; 0.10 less than or equal to (≤)Δ EQ-5D ≤0.24: minimal effect; 0.24≤ Δ EQ-5D \<0.31: satisfactory effect; Δ EQ-5D greater than or equal to (≥)0.31 points: pronounced effect.
General Health Score as Assessed by EQ-5D VAS Weeks 0, 4, 8, 12, 16, 20, and 24 Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality.
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D Weeks 0, 4, 8, 12, 16, 20, and 24 Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality. Positive response was defined as an increase of EQ-5D score by 0.1 or more i.e. it is a clinically significant increase.
Change in General Health Assessed by VAS Baseline and Week 24 Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality.
Disease Activity Score Based on 28-Joint Count (DAS28) Weeks 0, 4, 8, 12, 16, 20, and 24 DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
Change in DAS28 Score From Baseline to Week 24 Baseline and Week 24 Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment Weeks 0, 4, 8, 12, 16, 20, and 24 DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR mm/hour, and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Disease activity: 0=remission (DAS28 less than \[\<\] 2.6), I=low (DAS28 less than or equal to \[≤\]2.6 to \<3.2), II=moderate (DAS28=3.2 to 5.1), III=high (DAS28 greater than \[\>\]5.1).
European Quality of Life - 5 Dimensions (EQ-5D) Score Weeks 0, 4, 8, 12, 16, 20, and 24 EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression. Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response Weeks 0, 4, 8, 12, 16, 20, and 24 ACR20/50/70 response: ≥20%, ≥50%, or ≥70% improvement, respectively, in swollen/tender joint count (66 joints assessed for swelling and 68 joints assessed for tenderness) and in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase response: C-reactive protein (CRP) or ESR.
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 Weeks 4, 8, 12, 16, 20, and 24 The DAS28-based EULAR response criteria were used to measure individual response as no effect, good effect, and moderate effect, depending on the extent of change from baseline and the level of disease activity reached. Good effect: change from baseline \>1.2 with DAS28 score ≤3.2; moderate effect: change from baseline \>1.2 with DAS28 score 3.2 to 5.1 or change from baseline \>0.6 to \<1.2 with DAS28 score \<3.2; no effect: change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with DAS28 score \>5.1.
C-Reactive Protein Weeks 4, 8, 12, 16, 20, and 24 CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.
Trial Locations
- Locations (28)
Sverdlovsk Regional Clinical Hospital # 1; Rheumatology Dept
🇷🇺Ekaterinburg, Russian Federation
Republican Clinicodiagnostic Center
🇷🇺Izhevsk, Russian Federation
Kaliningrad Regional Clinical Hospital; Rheumatologic Department
🇷🇺Kaliningrad, Russian Federation
Republican Hospital Named After V.A. Baranov
🇷🇺Petrozavodsk, Russian Federation
Clinical hospital #1
🇷🇺Smolensk, Russian Federation
FGU Central Clinical Hospital with Polyclinic Administration President RF
🇷🇺Moscow, Russian Federation
GUZ Regional clinical hospital # 1
🇷🇺Krasnodar, Russian Federation
Kirov Regional Clinical Hospital; Reumatology Department
🇷🇺Kirov, Russian Federation
FSBI "FSCC of particularized sorts of medical care and medical technologies of FMBA"
🇷🇺Moscow, Russian Federation
Republican clinical hospital named after G.G. Kuvatov
🇷🇺UFA, Russian Federation
Voronezh Regional Clinical Hospital #1
🇷🇺Voronezh, Russian Federation
Republican clinical hospital of Karachai-Cherkess; Rheumatologic Department
🇷🇺Cherkess, Russian Federation
Head Clinical Hospital of Internal Affair Ministry of Russia
🇷🇺Moscow, Russian Federation
GMU Kursk regional clinical hospital
🇷🇺Kursk, Russian Federation
Chelyabinsk Regional Clinical Hospital; Rheumatology
🇷🇺Chelyabinsk, Russian Federation
Municipal Autonomous Institution of Healthcare "City Clinical Hospital #40"
🇷🇺Ekaterinburg, Russian Federation
State Institution of Healthcare Ulyanovsk Regional Clinical Hospital
🇷🇺Ulyanovsk, Russian Federation
SHI Yaroslavl Regional Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
SIH Nizhny Novgorod Regional Clinical Hospital n.a. Semashko
🇷🇺Nizhny Novgorod, Russian Federation
Vladimirskiy Regional Scientific Research Inst.
🇷🇺Moscow, Russian Federation
Rostov State Medical University; Cardiorheumatology Department
🇷🇺Rostov-na-Donu, Russian Federation
Glpu Tjumen Regional Clinical Hospital #1
🇷🇺Tjumen, Russian Federation
GUZ "Novgorod Regional Clinical Hospital"; Cardioreumatological
🇷🇺Veliky Novgorod, Russian Federation
Surgut Region Clinical Hospital
🇷🇺Surgut, Russian Federation
Budget Institution of Healthcare of Voronezh Region "Voronezh Regional Clinical Hospital #1"
🇷🇺Voronezh, Russian Federation
Irkutsk Regional Consulting and Diagnostic Clinical Center; Regional Center of Reumatolodic Deasise
🇷🇺Irkutsk, Russian Federation
War Veterans Regional Clinical Hospital;Therapy Department
🇷🇺Kemerovo, Russian Federation
FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences
🇷🇺Moscow, Russian Federation