Phase 3
Completed N=97
A Study of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Rheumatoid Arthritis
Source: ClinicalTrials.gov NCT01941095 ↗Enrolled (actual)
97
Serious AEs
7.2%
Results posted
Nov 2018
Primary outcomePrimary: Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24 — 40 percentage of participants
◆ Published Evidence
Established
37citations · ~5 / year
Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries.
Summary
This Phase IIIb, multicenter, open label, single arm study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab as monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active rheumatoid arthritis who are either naïve to or have an inadequate response to prior non-biologic or/and biologic DMARDs. The anticipated time on study treatment is 52 weeks. Those participants who will complete the 60-week study period and have achieved Disease Activity Score 28 (DAS28) remission or a good European League Against Rheumatism (EULAR) response at 52 weeks will be eligible to enter the extension phase until tocilizumab is commercially available and reimbursed in Greece.
Linked Publications (2)
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Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries.
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Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24 |
40 | — |
| SECONDARY Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 |
38.7; 34.2; 36.5; 36.5; 36.5; 35.2 | — |
| SECONDARY Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 |
5.1; 8.1; 4.1; 9.5; 6.9; 8.5 | — |
| SECONDARY Change From Baseline in DAS28-ESR up to Week 52 |
-0.99; -1.70; -2.20; -2.56; -2.59; -2.93 | — |
| SECONDARY Number of Participants With American College of Rheumatology 20 (ACR20) Response |
19; 19; 23; 9; 13; 16 | — |
| SECONDARY Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria |
9.4; 44.8; 45.8; 9.5; 38.9; 51.6 | — |
| SECONDARY Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 |
-3.41; -6.54; -8.72; -11.07; -13.47; -13.88 | — |
| SECONDARY Change From Baseline in TJC28 up to Week 52 |
-1.30; -3.26; -4.97; -5.82; -6.39; -7.03 | — |
| SECONDARY Change From Baseline in SJC28 up to Week 52 |
-1.82; -3.08; -4.71; -5.24; -5.79; -6.06 | — |
| SECONDARY Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation |
48.6 | — |
| SECONDARY Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation |
6; 10; 2 | — |
| SECONDARY Number of Participants With Anti-Tocilizumab Antibodies (ATA) |
7; 4; 0; 3; 0; 0 | — |
| SECONDARY Soluble Interleukin-6 Receptor (sIL-6R) Levels |
39450; 553.43; 572.03; 570.78; 537.73; 42850 | — |
| SECONDARY Tocilizumab Serum Levels |
0.38; 41.98; 44.67; 47.90; 45.37; 6.46 | — |
| SECONDARY PGA, Using VAS Score |
28.26; 27.57; 28.36; 32.28; 28.73; 24.40 | — |
| SECONDARY Patient Assessment of Pain, Using VAS Score |
46.40; 52.04; 49.87; 42.72; 37.21; 34.24 | — |
| SECONDARY HAQ-DI Score |
1.31; 1.22; 1.09; 0.91; 0.82; 0.72 | — |
| SECONDARY Percentage of Participants Who Received All Planned Study Medication (Compliance) |
66; 97.9; 100; 100; 98.9; 97.6 | — |
| SECONDARY Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score |
89.68; 91.83; 100.38; 103.16; 106.39; 110.17 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria
- Oral corticosteroids (less than or equal to [ /=] 4 weeks prior to baseline
- Permitted non biologic DMARDs are allowed if a stable dose for at least 4 weeks prior to baseline
- Receiving treatment on an outpatient basis, not including tocilizumab
- Females of childbearing potential and males with female partners of childbearing potential must agree to use a reliable means of contraception during the study; females of childbearing potential must use a reliable means of contraception for at least 3 month following the last dose of tocilizumab
Exclusion Criteria
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
- Rheumatic autoimmune disease other than rheumatoid arthritis; secondary Sjögren's syndrome with rheumatoid arthritis is permitted
- Functional Class 4 as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16
- Prior history of or current inflammatory joint disease other than rheumatoid arthritis
- Participants with lack of peripheral venous access
- Exposure to tocilizumab (either intravenous [IV] or SC) at any time prior to baseline
- Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of screening
- Previous treatment with any cell-depending therapies
- Treatment with IV gamma globulin, plasmapheresis within 6 months of baseline
- Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
- Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation
- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
- Any major episode of infection requiring hospitalization of treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- Active tuberculosis (TB) requiring treatment within the previous 3 years
- Positive for hepatitis B surface antigen or hepatitis C antibody
- Primary or secondary immunodeficiency (history of or currently active)
- Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years
- Pregnant or breast feeding women
- History of alcohol, drug or chemical abuse within 1 year prior to screening
- Neuropathies or other conditions that interfere with pain evaluation
Data sourced from ClinicalTrials.gov (NCT01941095) and the linked publication. 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. Informational only — not medical advice.