Rheumatoid Arthritis (RA) MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: RoActemra 20 mg/ml Concentrate for solution for infusion
Product Name: Tocilizumab
Product Code: RO4877533
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: T
Sponsors
Roche Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients at baseline with active rheumatoid arthritis (RA) and a DAS28 (ESR) of >3.2 and of =6 months duration, diagnosed according to the ACR (American College of Rheumatology) criteria of 1987. 2. Patients able and willing to give written informed consent to participate and comply with the requirements of the study; in addition, written consent for data protection (legal requirement in Germany: Datenschutz-rechtliche Einwilligung) must be provided. 3. Receiving treatment on an outpatient basis. 4. Age =18 years. 5. At screening and/or baseline either ESR =28mm/h or CRP =0.7mg/dL (SI: =7mg/L). 6. Receiving permitted DMARDs, one or more; current DMARD therapy must have been at a stable dose for at least 4 weeks prior to baseline. 7. Oral corticosteroids (=10mg/day prednisone or equivalent) are permitted if dose was stable for at least 4 weeks prior to baseline. 8. Women of child-bearing potential are allowed to participate in this trial only if using reliable, highly effective contraceptives (allowed methods of birth control, i.e. with a failure rate of less than 1 % per year, are implants, injectables, combined oral contraceptives, IUSs (only hormonal contraceptive coil), sexual abstinence or vasectomized partner. 9. Women of childbearing potential or less than one year after menopause (unless surgically steril) must have a negative pregnancy test (urine ß-HCG) at screening. Pregnancy test has to be repeated at baseline in case of ab-sence of menstruation or irregular menstrual cycle. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 385 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 115
Exclusion criteria
Exclusion criteria: Exclusion criteria related to general health 1. Major surgery (including joint surgery) within eight weeks prior to baseline or planned major surgery within the study duration (a maximum of 32 weeks following baseline) 2. Functional class IV as identified by the ACR classification of Functional Status in Rheumatoid Arthritis. 3. Rheumatic autoimmune disease other than RA, including SLE, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g. vasculitis, pulmonary fibrosis or Felty's syndrome). Sjögren's syndrome with RA is allowable. 4. Prior history of or current inflammatory joint disease other than RA (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, active Lyme disease). Exclusion criteria related to medications 5. Patients currently participating in another clinical trial or patients who have participated in another clinical trial within 30 days prior to screening (or five half-lifes of the IMP, whichever is longer) or patients who participated in this trial before. 6. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20). 7. Treatment with intravenous gamma globulin plasmapheresis or immunosorbent column (e.g. Prosorba®) within six months of base-line. 8. Intra-articular or parenteral corticosteroids within four weeks prior to baseline. Injection of intra-articular steroids while on study medication is discouraged, but may be used in a limited fashion. 9. Immunization with a live/attenuated vaccine within four weeks prior to baseline. 10. Previous treatment with TCZ, RTX, or other biologic DMARDs such as TNF-blockers. 11. Combination therapy with methotrexate (MTX) and leflunomide within 4 weeks prior to baseline. 12. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation. Exclusion criteria related to general safety 13. Severe heart failure (NYHA class IV) or severe, uncontrolled cardiac diseases. 14. History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies. 15. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (incl. obstructive pulmonary disease), renal, hepatic, endocrine (incl. uncontrolled diabetes mellitus) or gastrointestinal disease. 16. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids. 17. History of diverticulitis, diverticulosis requir-ing antibiotic treatment or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations or evidence of serious uncontrolled concomitant gastrointestinal disease. 18. Current liver disease as determined by principal investigator (patients with prior history of ALT elevation will not be excluded.) 19. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, granulomatous disease on chest X-ray (X-ray should not be older than 90 days related to treatment start), Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds), or any major episode of infection requiring
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the early efficacy of TCZ at week 16 defined as DAS28 remission (<2.6), after 4 courses of 8mg/kg TCZ treatment.;Secondary Objective: To assess: - the efficacy of RTX treatment in terms of improvement in commonly used RA outcome measures (DAS28 remission (<2.6), EULAR responses, ACR responses) at week 32 in patients not having responded to 4 courses of TCZ. The efficacy of TCZ treatment (EULAR responses especially late clinical remission, ACR responses) at week 32 in DMARD-IR patients.The effects of TCZ and RTX treatment on patient-reported outcomes. ?Safety will be assessed via reporting of incidences of adverse events and serious adverse events and the number and percentage of patients who discontinue study treatment due to AEs and SAEs. ?To correlate DAS28 response with B-cell panels. Due to character limitation - details see protocol;Primary end point(s): The primary endpoint is the rate of patients achieving DAS28 remission (<2.6) at week 16. | — |
Countries
Germany
Outcome results
None listed