RoActemra® (tocilizumab) plus methotrexate (MTX) in stable dosage in comparison with RoActemra® plus reducing (tapering) MTX dosages in patients with severe rheumatoid arthritis (RA) that have inadequate responded to a trial of two disease modifying anti-rheumatic drugs (DMARDs), including MTX and have not been previously treated with a biologic agent, such as a TNF inhibitor.
- Conditions
- Adult Rheumatoid Arthritis (RA)MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2011-005260-20-GB
- Lead Sponsor
- Roche Products Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 427
1.Male or non-pregnant, non-nursing female.
2.= 18 years of age.
3.Patients currently experiencing active severe RA (DAS28 >5.1) according to the EULAR/ACR criteria for the diagnosis of RA at start of treatment (week 0).
4.Patients should have inadequately responded to a trial of 2 DMARDs, including MTX (as defined by NICE) and have not been previously treated with a biologic agent, such as a TNF inhibitor. NICE define a trial of DMARDs (including MTX) as being normally of 6 months, with 2 months at standard dose.
5.Patients with a history of parenteral (subcutaneous or intramuscular) MTX prior to start of treatment (week 0) are eligible. However, prior to treatment (day 1) these patients must have been on a stable dose of oral MTX of at least 10 mg/week.
6.If patients are receiving an oral corticosteroid, the dose must have been = 10 mg/day prednisone (or equivalent) and stable for at least 25 out of 28 days prior to start of treatment (day 1).
7.Patients receiving treatment on an outpatient basis.
8.Patients able and willing to give written informed consent and comply with the requirements of the study protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 513
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 105
Disease
1.Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomisation
2.Rheumatic autoimmune disease other than RA. Patients with interstitial pulmonary fibrosis and Sjögren’s Syndrome with RA are permitted.
3.Functional class IV as defined by ACR Classification of Functional Status in RA
4.Prior history of/current inflammatory joint disease other than RA
Drug-specific
5.Treatment with leflunomide, or cholestyramine washout within 3 months prior to enrolment.
6.Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening
7.Previous treatment with RoActemra
8.Previous treatment with any biologic drug that is used in the treatment of RA
9.Any previous treatment with alkylating agents eg as cyclophosphamide or chlorambucil, or with total lymphoid irradiation
10.Treatment with IV gamma globulin, plasmapheresis or Prosorba column within 6 months before enrolment
11.Intra-articular/parenteral corticosteroids within 6 weeks prior to enrolment
12.Immunisation with a live/attenuated vaccine within 4 weeks prior to enrolment
Laboratory analyses (at screening)
13.Serum creatinine > 142 µmol/L (1.6 mg/dL) in female patients and > 168 µmol/L (1.9 mg/dL) in male patients
14.ALT (SGPT) or AST (SGOT)> 2 x ULN
15.Platelets< 100 x 109/L (100,000/mm3)
16. Haemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
17.White blood cells< 1.0 x 109/L (1000/mm3), ANC< 1.0 x 109/L (1000/mm3)
18. Absolute lymphocyte count< 0.5 x 109/L (500/mm3)
19.Positive hepatitis B virus surface antibody (HBsAg) or Hepatitis C virus (HCV) antibody
20.Total bilirubin> ULN
21.Triglycerides> 10 mmol/L (>900 mg/dL) at screening (non-fasting or fasting)
General medical
22.Pregnant women or breastfeeding mothers
23.Females of child-bearing potential not using reliable means of contraception
24.History of severe allergic/anaphylactic reactions to human, humanised, or murine monoclonal antibodies
25.Chest X-Ray (CXR) evidence of any clinically significant abnormality
26.Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (incl obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or GI disease
27.In patients with a history of diverticulitis or diverticulosis requiring antibiotic treatment, the treating physician needs to consider the benefit-risk ratio
28. History of chronic ulcerative lower GI disease such as Crohn’s disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforations
29.Uncontrolled disease states, eg asthma, psoriasis, or inflammatory bowel disease, where flares are commonly treated with oral/parenteral corticosteroids
30.Current liver disease as determined by investigator. Patients with prior history of ALT (SGPT) elevation are not exc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method