Multi-National Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis on Background Non-biologic DMARDs who have an Inadequate Response to Current Non-biologic DMARD and/or Anti-TNF Therapy

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000587-17-SE
• Date of registration: 21/05/2008
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: Multi-National Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis on Background Non-biologic DMARDs who have an Inadequate Response to Current Non-biologic DMARD and/or Anti-TNF Therapy
• Scientific title: Multi-National Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis on Background Non-biologic DMARDs who have an Inadequate Response to Current Non-biologic DMARD and/or Anti-TNF Therapy
• Date of first enrolment: 03/07/2008
• Target sample size: 1500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000587-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Portugal, Spain, Sweden, United Kingdom

Contacts

• Contact type: Public

• Contact type: Scientific

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or non-pregnant, non-nursing female
2. = 18 years of age
3. Diagnosis of active RA of = 6 months duration and moderate to severe disease activity defined as DAS28 > 3.2 at screening
4. Receiving treatment on an outpatient basis
5. Patients on = 1 non-biologic DMARDs and/or anti-TNF therapy (see section 6.1) at a stable dose for a period = 8 weeks at any time prior to treatment (baseline)
6. Patients with inadequate clinical response to a stable dose of non-biologic DMARD or anti-TNF therapy
7. If patients are receiving an oral corticosteroid, the dose must have been stable for at least 25 out of 28 days prior to treatment (baseline)
8. 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) 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:
Disease
1. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment
2. Rheumatic autoimmune disease other than RA, Sjögren’s Syndrome with RA is permitted
3. Functional class IV as defined by the ACR Classification of Functional Status
4. Prior history of or current inflammatory joint disease other than RA
Drug-specific
5. Treatment with any investigational agent or with anakinera, calcineurin inhibitors, mycophenolate, mofetil or mycophenolic acid within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening
6. Previous treatment with any cell-depleting therapies
7. Previous treatment with abatacept
8. Treatment with leuflunomide in combination with MTX.
9. Treatment with IV gamma globulin, plasmapheresis or Prosorba® column within 6 months before baseline
10. Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
11. Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
12. Previous treatment with TCZ (exception may be granted for single-dose exposure on a case by case basis)
13. Any previous treatment with alkylating agents

Laboratory analyses (at screening)
14. Serum creatinine > 124 µmol/L (1.4 mg/dL) in female patients and > 141 µmol/L (1.6 mg/dL) in male patients
15. ALT (SGPT) or AST (SGOT) > 1.5 ULN (If initial sample yields ALT [SGPT] or AST [SGOT] > 1.5 ULN, a second sample may be taken and tested during the screening period)
16. Platelet count < 100 x 10(9)/L (100,000/mm3)
17. Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
18. WBC count < 1.0 x 10(9)/L (3000/mm3), ANC < 0.5 x 10(9)/L (500/mm3)
19. ANC < 1 x 10(9)/L (1000/mm3)
20. Positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody
21. Total bilirubin > ULN (If initial sample yields bilirubin > ULN, a second sample may be taken and tested during the screening period)
22. Triglycerides > 10 mmol/L (> 900 mg/dL) at screening (non-fasted)

General medical
23. Pregnant women or nursing (breastfeeding) mothers
24. Females of child-bearing potential who are not using a reliable means of contraception, e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or IUD
25. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
26. CXR evidence of any clinically significant abnormality
27. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or GI disease
28. In patients with a history of diverticulitis or diverticulosis requiring antibiotic treatment, the treating physician needs to consider the benefit-risk ratio
29. A 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
30. Uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids
31. Current liver disease as determined by principal investigator. Patients with prior history of ALT (SGPT) elevation are not excluded
32. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, clinically significant abnormalities on CXR as determined by the investig

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis.
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: Actemra
Product Code: RO4877533 (TCZ)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumab
Current Sponsor code: RO4877533
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: • To assess the efficacy of TCZ monotherapy or in combination with non-biologic DMARDs

Primary end point(s): • Incidence of adverse events and serious adverse events during 24 weeks of TCZ monotherapy or combined treatment with TCZ and one or more of the background non-biologic disease modifying anti-rheumatic drugs (DMARDs) approved for rheumatoid arthritis (RA) in patients with moderate to severe active RA

Main Objective: • To assess the safety and tolerability of tocilizumab (TCZ) monotherapy or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs) in patients with moderate to severe active RA

Secondary ID(s)

2008-000587-17-GB

MA21573