Phase 3
N=188
A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis
Bottom Line
View on ClinicalTrials.gov: NCT00988221 ↗Enrolled (actual)
188
Serious AEs
13.8%
Results posted
Nov 2012
Primary outcome: Primary: Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40) — 48.1; 25.6 Percent of patients
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tocilizumab (Drug); Placebo (Drug)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Nov 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40) |
48.1; 25.6 | — |
| SECONDARY Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses in Part I of the Study (Baseline to Week 16) |
88.6; 76.5; 93.3; 89.4; 80.0; 70.6 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part I of the Study (Week 16) |
-61.48; -65.20; -72.61; -69.19 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part I of the Study (Week 16) |
-31.65; -55.56; -53.34; -49.46 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part I of the Study (Week 16) |
-63.36; -55.57; -72.96; -68.15 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part I of the Study (Week 16) |
-61.83; -49.87; -65.96; -62.42 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part I of the Study (Week 16) |
-70.98; -21.84; -70.87; -62.54 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at the End of Part I of the Study (Week 16) |
-54.48; -46.16; -49.07; -49.62 | — |
| SECONDARY Juvenile Arthritis Disease Activity Score (JADAS-27) at the End of Part I of the Study (Week 16) |
9.08; 12.25; 7.83; 8.82 | — |
| SECONDARY Pain Visual Analogue Scale (VAS) Score at the End of Part I of the Study (Week 16) |
21.9; 24.1; 20.3; 21.2 | — |
| SECONDARY Percent of Patients With Inactive Disease at the End of Part I of the Study (Week 16) |
20.0; 8.8; 18.5; 17.0 | — |
| SECONDARY Percent of Patients With an Elevated C-reactive Protein Concentration at Baseline That Had Normalized at the End of Part I of the Study (Week 16) |
76.9; 63.2; 87.0; 79.5 | — |
| SECONDARY Percent of Patients With an Elevated Erythrocyte Sedimentation Rate at Baseline That Had Normalized at the End of Part I of the Study (Week 16) |
82.6; 57.7; 87.7; 80.3 | — |
| SECONDARY Percent of Patients With an Elevated Platelet Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16) |
84.6; 55.6; 86.0; 78.4 | — |
| SECONDARY Percent of Patients With an Elevated White Blood Count at Baseline That Had Normalized at the End of Part I of the Study (Week 16) |
66.7; 66.7; 100.0; 75.0 | — |
| SECONDARY Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at the End of Part II of the Study (Week 40) |
54.3; 74.4; 51.9; 73.2; 42.0; 64.6 | — |
| SECONDARY Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part II of the Study (Week 40) |
-38.2; -45.6 | — |
| SECONDARY Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part II of the Study (Week 40) |
-32.4; -31.1 | — |
| SECONDARY Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part II of the Study (Week 40) |
-11.5; -14.5 | — |
| SECONDARY Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part II of the Study (Week 40) |
-8.1; -10.2 | — |
| SECONDARY Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at the End of Part II of the Study (Week 40) |
-14.0; -25.2 | — |
| SECONDARY Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) at the End of Part II of the Study (Week 40) |
-0.724; -0.804 | — |
| SECONDARY Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at the End of Part II of the Study (Week 40) |
-30.2; -31.5 | 0.0076 sig |
| SECONDARY Percent of Patients With Inactive Disease at the End of Part II of the Study (Week 40) |
17.3; 36.6 | 1.000 |
| SECONDARY Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Weeks 2, 52, and 104 |
55.6; 42.9; 45.5; 54.5; 52.4; 33.3 | — |
| SECONDARY Percent of Patients With 4 Baseline Disease Characteristics Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104 |
100.0; 100.0; 0.0; 96.0; 96.3; 100.0 | — |
| SECONDARY Change From Baseline in the Juvenile Arthritis Disease Activity Score-71 (JADAS-71) at Week 104 |
-31.40; -24.17; -25.42; -25.70; -26.05 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at Week 104 |
-97.65; -96.01; -90.42; -87.58; -89.70 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at Week 104 |
-97.01; -38.23; -83.06; -75.81; -75.35 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at Week 104 |
-98.57; -88.22; -76.43; -88.60; -87.73 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at Week 104 |
-98.57; -81.81; -76.66; -79.88; -81.30 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Erythrocyte Sedimentation Rate (ESR) at Week 104 |
-84.42; -89.21; -74.06; -73.85; -76.24 | — |
| SECONDARY Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Functional Ability at Week 104 |
-96.03; -79.50; -78.58; -73.34; -76.71 | — |
| SECONDARY Percent of Patients With a Minimally Important Improvement in the Children's Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Weeks 16, 40, 52, 80, and 104 |
77.8; 85.7; 81.8; 76.4; 78.0; 88.9 | — |
| SECONDARY C-reactive Protein Levels From Baseline to Week 104 |
1.726; 0.220; 1.077; 1.137; 1.129; 3.709 | — |
| SECONDARY Change From Baseline in the Pain Visual Analogue Scale (VAS) Score at Weeks 2, 40, 52, and 104 |
-11.4; -4.4; -6.1; -10.3; -9.4; -44.0 | — |
| SECONDARY Percent of Patients With Inactive Disease From Week 16 to Week 104 |
11.1; 42.9; 18.2; 20.0; 20.7; 44.4 | — |
| SECONDARY Percent of Patients in Clinical Remission From Week 40 to 104 |
0.0; 14.3; 0.0; 7.3; 6.1; 22.2 | — |
| SECONDARY Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses at Week 104 by Duration of Disease (< 2 Years, ≥ 2 Years) |
100.0; 100.0; 100.0; 88.2; 92.3; 100.0 | — |
| SECONDARY Oral Corticosteroid Dose at Baseline, Week 52, and Week 104 |
0.041; 0.095; 0.079; 0.055; 0.061; 0.021 | — |
| SECONDARY Methotrexate Dose at Baseline, Week 52, and Week 104 |
11.304; 17.562; 12.146; 8.768; 10.292; 9.247 | — |
| SECONDARY Height Standard Deviation Score at Baseline, Week 52, and Week 104 |
-0.57; -0.33; -0.51; -0.51; -0.15; -0.33 | — |
Summary
This 3-part study evaluated the efficacy and safety of tocilizumab in patients with active polyarticular-course juvenile idiopathic arthritis who have an inadequate response to, or were intolerant of methotrexate. In Part I of the study, all patients received intravenous (iv) infusions of tocilizumab (8 mg/kg for patients ≥ 30kg, 8 mg/kg or 10 mg/kg for patients < 30kg) every 4 weeks for 16 weeks. In Part II of the study, patients with an adequate response in Part I were randomized to receive either tocilizumab at the same dose as in Part I or placebo every 4 weeks for up to 24 weeks. In Part III of the study, patients received tocilizumab at the same dose as in Part I every 4 weeks for up to another 64 weeks. Standard of care therapy with or without non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, or methotrexate was continued throughout the study.
Eligibility Criteria
Inclusion Criteria
- Children/juveniles, 2-17 years of age.
- Polyarticular-course juvenile idiopathic arthritis (pcJIA) ≥ 6 months duration.
- Active disease (≥ 5 active joints, ≥ 3 with limitation of motion).
- Inadequate response to or inability to tolerate methotrexate.
- Methotrexate, oral corticosteroids, and non-steroidal anti-inflammatory drugs (NSAID) at stable dose(at least 8, 4, and 2 weeks,respectively) prior to baseline.
- Biologics discontinued, between at least 1 and 20 weeks prior to baseline, depending on biologic.
Exclusion Criteria
- Auto-immune, rheumatic disease or overlap syndrome other than pcJIA.
- Wheelchair bound or bedridden.
- Intra-articular, intramuscular, intravenous, or long-acting corticosteroids within 4 weeks prior to baseline.
- Disease-modifying anti-rheumatic drugs (DMARD) (other than methotrexate) within 4 weeks prior to baseline.
- Previous treatment with tocilizumab.
Data sourced from ClinicalTrials.gov (NCT00988221). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.