Effectiveness after 4 and 24 weeks and safety of tocilizumab in patients with active RA - TAMARA - Tocilizumab And DMARDs: Achievements in Rheumatoid Arthritis

• Conditions: Rheumatoid Arthritis; MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

• Registration Number: EUCTR2008-000105-11-DE
• Lead Sponsor: Roche Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-16
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Patients with rheumatoid arthritis of =6 months duration, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria.
2.Willingness to give written informed consent, written consent for data protection (legal requirement in Germany: datenschutz-rechtliche Einwilligung) and willingness to participate and to comply with the requirements of the study protocol.
3.Receiving treatment on an outpatient basis.
4.Age =18 years.
5.DAS28 of >3.2.
6.At screening either ESR =28 mm/h or
CRP =1 mg/dL.
7.Prior to baseline, will have discontinued: etanercept for =2 weeks, infliximab or adalimumab for =8 weeks, anakinra for =1 week.
8.Have received permitted DMARDs, 1 or more; current DMARD therapy must have been at a stable dose for at least 8 weeks prior to baseline.
9.Oral corticosteroids (=10 mg/day prednisone or equivalent) and NSAIDs (up to the maximum recommended dose) are permitted if dose stable for at least 4 weeks prior to baseline.
10.Women of child-bearing potential may participate in this trial only if using a reliable means of highly effective contraceptive method (allowed methods of birth control, i.e. with a failure rate of less than 1 % per year, are implants, injectables, combined oral contraceptives, IUDs (only hormonspirals), sexual abstinence or vasectomized partner).
11.Women of childbearing potential or less than one year after menopause (unless surgically steril) must have a negative pregnancy test (serum, ß-HCG) at screening.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Major surgery (including joint surgery) within eight weeks prior to screening or planned major surgery within six months following screening.
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 sig-nificant 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, Lyme disease).
Exclusion criteria related to medications:
5.Patients who participate currently in another clinical trial or patients who participated in another clinical trial during the last 30 days (or five half-lives, whichever is longer).
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 baseline.
8.Intraarticular or parenteral corticosteroids within six weeks prior to baseline.
9.Immunization with a live/attenuated vaccine within four weeks prior to baseline.
10.Previous treatment with tocilizumab.
11.Previous treatment with rituximab or abatacept.
12.Any previous treatment with alkylating agents such as cyclophosphamide or
chlorambucil, or with total lymphoid irradiation.
Exclusion criteria related to general safety:
13.History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
14.Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (incl. obstructive pulmonary disease), renal, hepatic, endocrine (incl. uncontrolled diabetes mellitus) or gastrointestine disease.
15.Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids.
16.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.
17.Current liver disease as determined by principal investigator. (Patients with prior history of ALT elevation will not be excluded.)
18.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 hospitalization or treatment with IV antibiotics within four weeks of screening or oral antibiotics within two weeks prior to screening.
19.Active tuberculosis (TB) requiring treatment within the previous 3 years. Subjects with a positive purified protein derivative tuberculin skin test (PPD) at screening are not eligible for the study unless they completed treatment for latent TB and had a negative CXR at enrollment.
20.Primary or secondary immunodeficiency (hi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the effectiveness of tocilizumab in combination with traditional DMARDs with regard to the clinical improvement in disease activity (achievement of LDAS) after 24 weeks' treatment in patients with active RA who have had an inadequate response to current traditional DMARD and/or anti-TNF therapy.;Secondary Objective: To assess the treatment effects in terms of improvement in the commonly used RA outcome measures (EULAR response, ACR responses).<br>To assess the safety of tocilizumab in combination with stable traditional DMARD therapy, with regard to adverse events and laboratory assessments and physical examination including vital signs. <br>To assess the effects on health-related quality of life outcomes (SF-36, HAQ-DI, FACIT-F and PTHFs) in this patient population. <br>;Primary end point(s): The primary endpoint is the rate of patients reaching DAS28 low disease (=3.2) at week 24.