Adult Rheumatoid Arthritis (RA) MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Roche Products Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To assess the efficacy of RoActemra with tapering MTX dosage versus RoActemra in combination with stable MTX dosage using EULAR and patient reported health assessments. To compare the incidence of anaemia in patients receiving RoActemra with tapering MTX dosage versus RoActemra in combination with stable MTX dosage. To compare change in work/productivity, as assessed by quality of life changes in patients receiving RoActemra with tapering MTX dosage versus RoActemra in combination with stable MTX dosage. To compare the safety of RoActemra with tapering MTX dosage versus RoActemra in combination with stable MTX dosage, with regards to adverse events and laboratory assessments. To assess the proportion of patients able to discontinue MTX. ;Main Objective: To compare the proportion of patients who maintain good/ moderate European League Against Rheumatism (EULAR) response between weeks 24 and week 56: in patients receiving RoActemra in combination with a tapering dose of MTX versus patients receiving RoActemra in combination with a stable dose of MTX.;Primary end point(s): Proportion of patients maintaining previous disease activity (EULAR response) from week 24 (time of randomisation) to week 56.;Timepoint(s) of evaluation of this end point: Week 56 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in DAS28 score from week 24 (time of randomisation) to week 56, between the 2 randomisation arms. Proportion of patients who achieve score of =1 in TJC, SJC at week 56. Proportion of patients who achieve a DAS28 =3.2 at week 56. Proportion of patients who achieve DAS28 remission (DAS28 < 2.6) at week 56. Proportion of patients who achieve cDAS = 1.2 at week 56. Proportion of patients who achieve CDAI remission (CDAI< 2.8) at week 56. Proportion of patients who achieve SDAI remission (SDAI < 3.3) at week 56. Improvement in physical function (HAQ, FACIT, SF 12) at week 56. Change in work/productivity (WPAI-SHP score) at week 56. Safety outcome measures: Incidence, nature and severity of adverse events. Incidence of MTX related side effects prior to (week 0 to 24) and after (week 28 to 56) randomisation and between randomisation arms. Change in haemoglobin from week 0 to weeks 24 and 56. Incidence of AEs of special interest: 1.Infections including all opportunistic infections and non-serious infections as defined by those treated with IV anti-infectives 2.Myocardial infarction/acute coronary syndrome 3.Gastrointestinal perforations and related events 4.Malignancies 5.Anaphylaxis/Hypersensitivity reactions 6.Demyelinating disorders 7.Stroke 8.Bleeding events 9.Hepatic events Incidence of anti-TCZ antibodies (immunogenicity testing). Patient reported outcome measures: Improvement in physical function (HAQ scire, FACIT, SF-12), WPAI-SHP score. ;Timepoint(s) of evaluation of this end point: Weeks 24 and 52 | — |
Countries
United Kingdom
Contacts
Public ContactClinical Projects Group
Roche Products Limited
Outcome results
None listed