A Phase 4 interventional study of tocilizumab [RoActemra/Actemra] in Rheumatoid Arthritis, sponsored by Hoffmann-La Roche. Completed at 9 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-07-22.
Sponsored by Hoffmann-La Roche · Phase 4, Interventional, and Treatment
This open-label single-arm study will evaluate the safety, tolerability and efficacy of tocilizumab [RoActemra/Actemra] in patients with moderate to severe rheumatoid arthritis who experience an inadequate clinical response to a stable dose of non-biologic disease modifying anti-rheumatic drugs (DMARD) or anti-tumor necrosis factors (TNFs). RoActemra/Actemra will be administered as a monotherapy or in combination with DMARDs. RoActemra/Actemra will be administered as intravenous infusion at a dose of 8 mg/kg every 4 weeks for a total of 6 infusions. The anticipated time on study treatment is 24 weeks. The target sample size is 50-150 patients.
3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.
This study's enrollment of 95 is close to the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.
Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.
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Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg iv infusion, every 4 weeks for a total of 6 infusions
Percentage of Participants Reporting Any Adverse Event - Overall Summary of Events
Percentage of participants with a serious adverse event (SAE), who died, with an adverse event (AE), or study drug related AE during the study.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24
Percentage of Participants by Disease Activity Score Based on 28-Joint Count (DAS28) Category
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and global health assessment (participant rated global assessment of disease activity using 10-mm Visual analog scale - VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A DAS28 score of greater than (\>)5.1 indicated high disease activity, a score of \>3.2 but less than or equal to (≤)5.1 indicated moderate disease activity, a score of greater than or equal to (≥)2.6 but ≤3.2 indicated low disease activity, and a score of less than \<2.6 indicated disease remission. Week 24 is the Follow-Up visit.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants Achieving a Clinically Meaningful Improvement as Measured by DAS28
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) 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. Participants achieved a clinically meaningful improvement in DAS28 if there was a reduction of at least 1.2 units from baseline.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Time to DAS28 Response by DAS28 Category
Time to response is the number of days from date of first infusion to date of event. DAS28 response was defined as achievement of Low Disease Activity (DAS28 ≥2.6 to ≤3.2), Remission (DAS28 \<2.6), or Clinically Meaningful Improvement (change of \>1.2 from baseline).
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at Least 0.22 Units
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.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants With Improvement in Physical Function by HAQ-DI Category
Physical function 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. The HAQ-DI score at every visit was categorized into none to mild disability (HAQ-DI \<1), moderate disability (1≤ HAQ-DI \<2) and severe disability (HAQ-DI ≥2). The percentages of the participants falling in each of these categories with respect to the visits were determined.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
HAQ-DI Score by 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=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..
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
C-Reactive Protein (CRP) Values by Study Visit
CRP is an acute phase inflammatory marker. The serum concentration of CRP is measured in milligrams per liter (mg/L). A reduction in the level is considered an improvement.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Erythrocyte Sedimentation Rate
ESR (measured in mm/hr) is an inflammation marker used to determine acute phase response.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
| Milestone | Tocilizumab 8 Milligrams Per Kilogram (mg/kg) |
|---|---|
| Started | 95 |
| Completed | 88 |
| Not completed | 7 |
| Withdrew: Lost to follow-up | 3 |
| Withdrew: Adverse event | 1 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Protocol violation | 1 |
| Withdrew: Lack of efficacy | 1 |
Percentage of participants with a serious adverse event (SAE), who died, with an adverse event (AE), or study drug related AE during the study.
| percentage of participants | Tocilizumab 8 mg/kg |
|---|---|
| With an SAE | 8.4 |
| Who Died | 0 |
| With any drug-related AE | 38.9 |
| With any AE | 45.3 |
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and global health assessment (participant rated global assessment of disease activity using 10-mm Visual analog scale - VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A DAS28 score of greater than (\>)5.1 indicated high disease activity, a score of \>3.2 but less than or equal to (≤)5.1 indicated moderate disease activity, a score of greater than or equal to (≥)2.6 but ≤3.2 indicated low disease activity, and a score of less than \<2.6 indicated disease remission. Week 24 is the Follow-Up visit.
| percentage of participants | Tocilizumab 8 mg/kg |
|---|---|
| High Disease Activity, Baseline (n=95) | 66.3 |
| High Disease Activity, Week 4 (n=93) | 15.1 |
| High Disease Activity, Week 8 (n=91) | 5.5 |
| High Disease Activity, Week 12 (n=89) | 2.2 |
| High Disease Activity, Week 16 (n=89) | 3.4 |
| High Disease Activity, Week 20 (n=88) | 1.1 |
| High Disease Activity, Week 24 (n=95) | 0 |
| Moderate Disease Activity, Baseline (n=95) | 33.7 |
| Moderate Disease Activity, Week 4 (n=93) | 48.4 |
| Moderate Disease Activity, Week 8 (n=91) | 36.3 |
| Moderate Disease Activity, Week 12 (n=89) | 23.6 |
| Moderate Disease Activity, Week 16 (n=89) | 11.2 |
| Moderate Disease Activity, Week 20 (n=88) | 10.2 |
| Moderate Disease Activity, Week 24 (n=95) | 7.4 |
| Low Disease Activity, Baseline (n=95) | 0.0 |
| Low Disease Activity, Week 4 (n=93) | 26.9 |
| Low Disease Activity, Week 8 (n=91) | 26.4 |
| Low Disease Activity, Week 12 (n=89) | 36.0 |
| Low Disease Activity, Week 16 (n=89) | 16.9 |
| Low Disease Activity Week 20 (n=88) | 15.9 |
| Low Disease Activity Week 24 (n=95) | 23.2 |
| Remission Baseline (n=95) | 0 |
| Remission Week 4 (n=93) | 9.7 |
| Remission Week 8 (n=91) | 31.9 |
| Remission Week 12 (n=89) | 38.2 |
| Remission Week 16 (n=89) | 67.4 |
| Remission Week 20 (n=88) | 67.4 |
| Remission Week 24 (n=95) | 64.2 |
DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) 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. Participants achieved a clinically meaningful improvement in DAS28 if there was a reduction of at least 1.2 units from baseline.
| percentage of participants | Tocilizumab 8 mg/kg |
|---|---|
| Week 4 (n=93) | 82.8 |
| Week 8 (n=91) | 92.3 |
| Week 12 (n=89) | 95.5 |
| Week 16 (n=89) | 95.5 |
| Week 20 (n=88) | 94.3 |
| Week 24 (n=95) | 91.6 |
Time to response is the number of days from date of first infusion to date of event. DAS28 response was defined as achievement of Low Disease Activity (DAS28 ≥2.6 to ≤3.2), Remission (DAS28 \<2.6), or Clinically Meaningful Improvement (change of \>1.2 from baseline).
| days | Tocilizumab 8 mg/kg |
|---|---|
| Clinically meaningful Improvement in DAS28 | 36.430 ± 2.355 |
| Low disease activity (≥2.6 to ≤3.2) | 75.261 ± 5.587 |
| Remission (<2.6) | 89.945 ± 4.395 |
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.
| percentage of participants | Tocilizumab 8 mg/kg |
|---|---|
| Week 4 (n=93) | 61.3 |
| Week 8 (n=91) | 72.5 |
| Week 12 (n=89) | 87.6 |
| Week 16 (n=89) | 93.3 |
| Week 20 (n=88) | 92.0 |
| Week 24 (n=95) | 83.2 |
Physical function 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. The HAQ-DI score at every visit was categorized into none to mild disability (HAQ-DI \<1), moderate disability (1≤ HAQ-DI \<2) and severe disability (HAQ-DI ≥2). The percentages of the participants falling in each of these categories with respect to the visits were determined.
| percentage of participants | Tocilizumab 8 mg/kg |
|---|---|
| HAQ-DI <1 Baseline (n=95) | 13.7 |
| HAQ-DI <1 Week 4 (n=93) | 36.6 |
| HAQ-DI <1 Week 8 (n=91) | 50.5 |
| HAQ-DI <1 Week 12 (n=89) | 60.7 |
| HAQ-DI <1 Week 16 (n=89) | 73.0 |
| HAQ-DI <1 Week 20 (n=88) | 80.7 |
| HAQ-DI <1 Week 24 (n=95) | 71.6 |
| ≤1 HAQ-DI <2 Baseline (n=95) | 61.1 |
| ≤1 HAQ-DI <2 Week 4 (n=93) | 46.2 |
| ≤1 HAQ-DI <2 Week 8 (n=91) | 39.6 |
| ≤1 HAQ-DI <2 Week 12 (n=89) | 34.8 |
| ≤1 HAQ-DI <2 Week 16 (n=89) | 25.8 |
| ≤1 HAQ-DI <2 Week 20 (n=88) | 15.9 |
| ≤1 HAQ-DI <2 Week 24 (n=95) | 15.8 |
| HAQ-DI ≥2 Baseline (n=95) | 24.2 |
| HAQ-DI ≥2 Week 4 (n=93) | 17.2 |
| HAQ-DI ≥2 Week 8 (n=91) | 9.9 |
| HAQ-DI ≥2 Week 12 (n=89) | 4.5 |
| HAQ-DI ≥2 Week 16 (n=89) | 1.1 |
| HAQ-DI ≥2 Week 20 (n=88) | 2.3 |
| HAQ-DI ≥2 Week 24 (n=95) | 3.2 |
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..
| scores on a scale | Tocilizumab 8 mg/kg |
|---|---|
| Baseline (n=95) | 1.570 ± 0.6157 |
| Week 4 (n=93) | 1.185 ± 0.7092 |
| Week 8 (n=91) | 0.972 ± 0.6236 |
| Week 12 (n=89) | 0.805 ± 0.5634 |
| Week 16 (n=89) | 0.680 ± 0.4804 |
| Week 20 (n=88) | 0.576 ± 0.4812 |
| Week 24 (n=95) | 0.551 ± 0.5139 |
CRP is an acute phase inflammatory marker. The serum concentration of CRP is measured in milligrams per liter (mg/L). A reduction in the level is considered an improvement.
| mg/L | Tocilizumab 8 mg/kg |
|---|---|
| Baseline | 26.90 ± 34.406 |
| Week 4 | 8.49 ± 29.074 |
| Week 8 | 7.84 ± 23.116 |
| Week 12 | 5.32 ± 10.614 |
| Week 16 | 5.18 ± 8.105 |
| Week 20 | 5.62 ± 8.618 |
| Week 24 | 8.59 ± 21.702 |
ESR (measured in mm/hr) is an inflammation marker used to determine acute phase response.
| mm/hr | Tocilizumab 8 mg/kg |
|---|---|
| Baseline | 45.27 ± 29.227 |
| Week 4 | 10.61 ± 14.118 |
| Week 8 | 7.66 ± 11.554 |
| Week 12 | 7.52 ± 10.361 |
| Week 16 | 5.83 ± 6.386 |
| Week 20 | 6.60 ± 8.576 |
| Week 24 | 9.17 ± 12.311 |
Collected over Adverse events data were collected from the date of first dose of study drug administration to the end of study at Week 24.. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Tocilizumab | — | 8/95 (8.4%) | 43/95 (45.3%) |
| Event | Tocilizumab |
|---|---|
| Metabolism and nutrition disordersMetabolism and nutrition disorders | 3/95 |
| InvestigationsInvestigations | 2/95 |
| Musculoskeletal and connective tissue disorderMusculoskeletal and connective tissue disorders | 2/95 |
| Infection and infestationInfections and infestations | 1/95 |
| Renal and urinary disordersRenal and urinary disorders | 1/95 |
| Event | Tocilizumab |
|---|---|
| InvestigationsInvestigations | 29/95 |
| Blood and lymphatic system disordersBlood and lymphatic system disorders | 7/95 |
| Infections and infestationsInfections and infestations | 7/95 |
| Metabolism and nutrition disordersMetabolism and nutrition disorders | 7/95 |
| Skin and subcutaneous tissue disordersSkin and subcutaneous tissue disorders | 5/95 |
| Gastrointestinal disordersGastrointestinal disorders | 4/95 |
| Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders | 4/95 |
| General disorders and administration site conditionsGeneral disorders | 3/95 |
| Nervous system disordersNervous system disorders | 3/95 |
| Respiratory, thoracic, and mediastinal disordersRespiratory, thoracic and mediastinal disorders | 3/95 |
All the participants who were administered treatment at each visit were considered during the analysis.
| Age, Continuous(years) | Tocilizumab 8 mg/kg |
|---|---|
| Mean | 44.89 ± 13.677 |
| Sex: Female, Male(Participants) | Tocilizumab 8 mg/kg |
|---|---|
| Female | 78 |
| Male | 17 |
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