A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs.

Local Open-label Multicenter Study to Evaluate the Quality of Life in Patients With Moderate to Severe Active Rheumatoid Arthritis and an Inadequate Response to DMARDs When Adding Tocilizumab (TCZ)

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: tocilizumab [RoActemra/Actemra]; Drug: DMARDs (disease-modifying antirheumatic drugs)

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Chelyabinsk, Russian Federation, 454076
    • Chelyabinsk Regional Clinical Hospital; Rheumatology
  • Cherkess, Russian Federation, 369000
    • Republican clinical hospital of Karachai-Cherkess; Rheumatologic Department
  • Ekaterinburg, Russian Federation, 620102
    • Municipal Autonomous Institution of Healthcare "City Clinical Hospital #40"
  • Ekaterinburg, Russian Federation, 620102
    • Sverdlovsk Regional Clinical Hospital # 1; Rheumatology Dept
  • Irkutsk, Russian Federation, 664047
    • Irkutsk Regional Consulting and Diagnostic Clinical Center; Regional Center of Reumatolodic Deasise
  • Izhevsk, Russian Federation, 426009
    • Republican Clinicodiagnostic Center
  • Kaliningrad, Russian Federation, 236016
    • Kaliningrad Regional Clinical Hospital; Rheumatologic Department
  • Kemerovo, Russian Federation, 650099
    • War Veterans Regional Clinical Hospital;Therapy Department
  • Kirov, Russian Federation, 610028
    • Kirov Regional Clinical Hospital; Reumatology Department
  • Krasnodar, Russian Federation, 350086
    • GUZ Regional clinical hospital # 1
  • Kursk, Russian Federation, 305007
    • GMU Kursk regional clinical hospital
  • Moscow, Russian Federation, 123060
    • Head Clinical Hospital of Internal Affair Ministry of Russia
  • Moscow, Russian Federation, 129110
    • Vladimirskiy Regional Scientific Research Inst.
  • Moscow, Russian Federation, 115522
    • FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences
  • Moscow, Russian Federation, 115682
    • FSBI "FSCC of particularized sorts of medical care and medical technologies of FMBA"
  • Moscow, Russian Federation, 121359
    • FGU Central Clinical Hospital with Polyclinic Administration President RF
  • Nizhny Novgorod, Russian Federation, 603126
    • SIH Nizhny Novgorod Regional Clinical Hospital n.a. Semashko
  • Petrozavodsk, Russian Federation, 185019
    • Republican Hospital Named After V.A. Baranov
  • Rostov-na-Donu, Russian Federation, 344022
    • Rostov State Medical University; Cardiorheumatology Department
  • Smolensk, Russian Federation, 214001
    • Clinical hospital #1
  • Surgut, Russian Federation, 628408
    • Surgut Region Clinical Hospital
  • Tjumen, Russian Federation, 625023
    • Glpu Tjumen Regional Clinical Hospital #1
  • UFA, Russian Federation, 450005
    • Republican clinical hospital named after G.G. Kuvatov
  • Ulyanovsk, Russian Federation, 432063
    • State Institution of Healthcare Ulyanovsk Regional Clinical Hospital
  • Veliky Novgorod, Russian Federation, 173008
    • GUZ "Novgorod Regional Clinical Hospital"; Cardioreumatological
  • Voronezh, Russian Federation, 394066
    • Voronezh Regional Clinical Hospital #1
  • Voronezh, Russian Federation, 394066
    • Budget Institution of Healthcare of Voronezh Region "Voronezh Regional Clinical Hospital #1"
  • Yaroslavl, Russian Federation, 150062
    • SHI Yaroslavl Regional Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: tocilizumab [RoActemra/Actemra]; 8 mg/kg iv every 4 weeks for 24 weeks; Drug: DMARDs (disease-modifying antirheumatic drugs); stable doses at investigator's prescription

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health Assessment Questionnaire (HAQ) Score	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.	Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment	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.	Weeks 4, 8, 12, 16, 20, and 24
Change in HAQ Score at 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.	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Score as Assessed by Visual Analogue Scale (VAS)	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.	Weeks 0, 4, 8, 12, 16, 20, and 24
European Quality of Life - 5 Dimensions (EQ-5D) Score	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.	Weeks 0, 4, 8, 12, 16, 20, and 24
Change in EQ-5D Score at Week 24 From Baseline	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.	Baseline and Week 24
General Health Score as Assessed by EQ-5D VAS	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.	Weeks 0, 4, 8, 12, 16, 20, and 24
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D	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.	Weeks 0, 4, 8, 12, 16, 20, and 24
Change in General Health Assessed by VAS	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.	Baseline and Week 24
Disease Activity Score Based on 28-Joint Count (DAS28)	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.	Weeks 0, 4, 8, 12, 16, 20, and 24
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	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).	Weeks 0, 4, 8, 12, 16, 20, and 24
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response	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.	Weeks 0, 4, 8, 12, 16, 20, and 24
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28	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.	Weeks 4, 8, 12, 16, 20, and 24
C-Reactive Protein	CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.	Weeks 4, 8, 12, 16, 20, and 24
Erythrocyte Sedimentation Rate	ESR (mm/hr) is used to determine the acute phase response.	Weeks 4, 8, 12, 16, 20, and 24

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2009
• Primary Completion (Actual): February 14, 2011
• Study Completion (Actual): February 14, 2011

Study Registration Dates

• First Submitted: October 15, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (Estimate): October 16, 2009

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: February 28, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Antirheumatic Agents
• Other Study ID Numbers: ML22665