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NCT00996203

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

Completed Phase 4 Results posted Last updated 29 March 2018
What this trial tests

Phase 4 trial testing tocilizumab [RoActemra/Actemra] in Rheumatoid Arthritis in 201 participants. Completed in 14 February 2011.

Timeline
31 October 2009
Primary endpoint
14 February 2011
14 February 2011

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment201
Start date31 October 2009
Primary completion14 February 2011
Estimated completion14 February 2011
Sites28 locations across Russia

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Rheumatoid Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Health Assessment Questionnaire (HAQ) Score Primary · 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 withd

Week 0 (n=201)
GroupValue95% CI
Tocilizumab1.93± 0.60
Week 4 (n=199)
GroupValue95% CI
Tocilizumab1.49± 0.65
Week 8 (n=198)
GroupValue95% CI
Tocilizumab1.22± 0.63
Week 12 (n=196)
GroupValue95% CI
Tocilizumab1.08± 0.62
Week 16 (n=193)
GroupValue95% CI
Tocilizumab1.00± 0.60
Week 20 (n=193)
GroupValue95% CI
Tocilizumab0.90± 0.61
Week 24 (n=193)
GroupValue95% CI
Tocilizumab0.84± 0.62
Withdrawal visit (n=6)
GroupValue95% CI
Tocilizumab1.32± 1.13
Pain Score as Assessed by Visual Analogue Scale (VAS) Secondary · 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.

Week 0 (n=201)
GroupValue95% CI
Tocilizumab63.82± 16.71
Week 4 (n=199)
GroupValue95% CI
Tocilizumab46.36± 20.57
Week 8 (n=198)
GroupValue95% CI
Tocilizumab36.48± 18.94
Week 12 (n=196)
GroupValue95% CI
Tocilizumab31.90± 19.83
Week 16 (n=193)
GroupValue95% CI
Tocilizumab26.92± 18.87
Week 20 (n=193)
GroupValue95% CI
Tocilizumab24.63± 19.09
Week 24 (n=193)
GroupValue95% CI
Tocilizumab21.96± 18.87
Withdrawal visit (n=6)
GroupValue95% CI
Tocilizumab34.50± 22.00
European Quality of Life - 5 Dimensions (EQ-5D) Score Secondary · 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.

Week 0 (n=200)
GroupValue95% CI
Tocilizumab0.29± 0.31
Week 4 (n=199)
GroupValue95% CI
Tocilizumab0.49± 0.24
Week 8 (n=198)
GroupValue95% CI
Tocilizumab0.57± 0.20
Week 12 (n=196)
GroupValue95% CI
Tocilizumab0.61± 0.21
Week 16 (n=193)
GroupValue95% CI
Tocilizumab0.64± 0.19
Week 20 (n=193)
GroupValue95% CI
Tocilizumab0.66± 0.18
Week 24 (n=193)
GroupValue95% CI
Tocilizumab0.69± 0.20
Withdrawal visit (n=4)
GroupValue95% CI
Tocilizumab0.61± 0.07
Change in EQ-5D Score at Week 24 From Baseline Secondary · 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 assessm

GroupValue95% CI
Tocilizumab0.41± 0.33
General Health Score as Assessed by EQ-5D VAS Secondary · 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.

Week 0 (n=201)
GroupValue95% CI
Tocilizumab39.27± 18.03
Week 4 (n=199)
GroupValue95% CI
Tocilizumab50.93± 18.78
Week 8 (n=198)
GroupValue95% CI
Tocilizumab61.79± 43.45
Week 12 (n=196)
GroupValue95% CI
Tocilizumab66.13± 19.91
Week 16 (n=193)
GroupValue95% CI
Tocilizumab70.48± 19.39
Week 20 (n=192)
GroupValue95% CI
Tocilizumab73.31± 19.58
Week 24 (n=193)
GroupValue95% CI
Tocilizumab76.22± 19.25
Withdrawal visit (n=4)
GroupValue95% CI
Tocilizumab60.50± 27.77
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D Secondary · 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.

Week 4 (n=198)
GroupValue95% CI
Tocilizumab42.9
Week 8 (n=198)
GroupValue95% CI
Tocilizumab55.6
Week 12 (n=196)
GroupValue95% CI
Tocilizumab60.2
Week 16 (n=193)
GroupValue95% CI
Tocilizumab65.8
Week 20 (n=193)
GroupValue95% CI
Tocilizumab68.4
Week 24 (n=193)
GroupValue95% CI
Tocilizumab73.1
Change in General Health Assessed by VAS Secondary · 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.

GroupValue95% CI
Tocilizumab37.3± 25.75
Disease Activity Score Based on 28-Joint Count (DAS28) Secondary · 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.

Week 0 (n=199)
GroupValue95% CI
Tocilizumab6.748± 0.852
Week 4 (n=197)
GroupValue95% CI
Tocilizumab4.665± 1.227
Week 8 (n=196)
GroupValue95% CI
Tocilizumab3.777± 1.279
Week 12 (n=193)
GroupValue95% CI
Tocilizumab3.347± 1.208
Week 16 (n=193)
GroupValue95% CI
Tocilizumab2.956± 1.230
Week 20 (n=192)
GroupValue95% CI
Tocilizumab2.762± 1.111
Week 24 (n=191)
GroupValue95% CI
Tocilizumab2.637± 1.157
Change in DAS28 Score From Baseline to Week 24 Secondary · Baseline and Week 24
GroupValue95% CI
Tocilizumab4.097± 1.289
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment Primary · 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.

Week 4 ≥20% (n=199)
GroupValue95% CI
Tocilizumab51.8
Week 4 ≥50% (n=199)
GroupValue95% CI
Tocilizumab15.6
Week 4 ≥70% (n=199)
GroupValue95% CI
Tocilizumab5.0
Week 8 ≥20% (n=198)
GroupValue95% CI
Tocilizumab72.2
Week 8 ≥50% (n=198)
GroupValue95% CI
Tocilizumab28.8
Week 8 ≥70% (n=198)
GroupValue95% CI
Tocilizumab13.6
Week 12 ≥ 20% (n=196)
GroupValue95% CI
Tocilizumab83.7
Week 12 ≥50% (n=196)
GroupValue95% CI
Tocilizumab42.3
Change in HAQ Score at Week 24 Primary · 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.

GroupValue95% CI
Tocilizumab1.11± 0.66
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment Secondary · 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).

Week 0 moderate activity (n=199)
GroupValue95% CI
Tocilizumab2.5
Week 0 high activity (n=199)
GroupValue95% CI
Tocilizumab97.5
Week 4 remission (n=197)
GroupValue95% CI
Tocilizumab3.0
Week 4 low activity (n=197)
GroupValue95% CI
Tocilizumab9.6
Week 4 moderate activity (n=197)
GroupValue95% CI
Tocilizumab52.8
Week 4 high activity (n=197)
GroupValue95% CI
Tocilizumab34.5
Week 8 remission (n=196)
GroupValue95% CI
Tocilizumab17.9
Week 8 low activity (n=196)
GroupValue95% CI
Tocilizumab15.3

Adverse events — posted to ClinicalTrials.gov

Time frame: From baseline Visit up to 24 weeks or until withdrawal. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tocilizumab
Serious: 12/201 (6%)
Deaths:

Serious adverse events (14 terms)

ReactionSystemTocilizumab
Erysipelatous inflammationSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
Cervical myelopathyNervous system disorders
Localized infectionInfections and infestations
Wound infectionInfections and infestations
Acute pyelonephritisInfections and infestations
Subcutaneous abscessInfections and infestations
PneumoniaInfections and infestations
FractureMusculoskeletal and connective tissue disorders
Hemorrhagic anemiaVascular disorders
Venous thrombosisVascular disorders
Toxic hepatitisHepatobiliary disorders
Chronic bronchitisRespiratory, thoracic and mediastinal disorders
Anaphylactic shockImmune system disorders
Other adverse events (35 terms — click to expand)

ReactionSystemTocilizumab
Alanine aminotransferase increasedInvestigations
Transaminases increasedInvestigations
Respiratory tract infectionInfections and infestations
Respiratory tract infection viralInfections and infestations
Aspartate aminotransferase increasedInvestigations
ThrombocytopeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Oral herpesInfections and infestations
PharyngitisInfections and infestations
Blood pressure increasedInvestigations
LymphostasisBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
KeratitisEye disorders
DiarrhoeaGastrointestinal disorders
HyperbilirubinaemiaHepatobiliary disorders
HypersensitivityImmune system disorders
Acute tonsillitisInfections and infestations
OnychomycosisInfections and infestations
TracheitisInfections and infestations
HypercholesterolaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Lower limb fractureMusculoskeletal and connective tissue disorders
Upper limb fractureMusculoskeletal and connective tissue disorders
SynovitisMusculoskeletal and connective tissue disorders
Pyelonephritis chronicRenal and urinary disorders
Renal colicRenal and urinary disorders
ProstatitisReproductive system and breast disorders
Bronchitis chronicRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Skin reactionsSkin and subcutaneous tissue disorders
Tooth extractionSurgical and medical procedures
HaemorrhoidsVascular disorders
HypertensionVascular disorders

Most-reported serious reactions: Erysipelatous inflammation, Thrombocytopenia, Cervical myelopathy, Localized infection, Wound infection, Acute pyelonephritis, Subcutaneous abscess, Pneumonia.

Data from ClinicalTrials.gov NCT00996203 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

Verify or expand the search:

Other trials of tocilizumab [RoActemra/Actemra]

Trials testing the same drug.

Other recruiting trials for Rheumatoid Arthritis

Currently open trials in the same condition.

Other Hoffmann-La Roche trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00996203.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing