Extension Phase of the 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. - this is an extension study to MA21573

• Register: EUCTR
• Last refreshed on: 17 December 2012
• Main ID: EUCTR2008-006924-68-PT
• Date of registration: 17/03/2009
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: Extension Phase of the 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. - this is an extension study to MA21573
• Scientific title: Extension Phase of the 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. - this is an extension study to MA21573
• Date of first enrolment: 18/05/2009
• Target sample size: 1200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-006924-68
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Czech Republic, France, Hungary, Italy, Netherlands, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible for this trial, patients must meet all of the following criteria:

1. Completed the 24-week MA21573 core study, had at least a moderate response (EULAR definition criteria) and no AEs, SAEs or conditions that lead to unacceptable risk of continued treatment. Patients should be scheduled to receive the first tocilizumab (TCZ) infusion in MA22460 between 4 and 16 weeks after the last iv infusion in the core study.
2. Willing to give written informed consent for participation in the extension study
3. Able and willing to comply with the requirements of the extension 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:
Patients with any of the following criteria will not be eligible to participate in the study:

Disease:
1. Functional class IV as defined by the ACR Classification of Functional Status in RA (largely or wholly incapacitated with patient bedridden or confined to wheel chair, permitting little or no self-care).
If female and of child-bearing potential, the patient must have a negative urine pregnancy test at day 1.

Laboratory analyses (at transition from core study):
2. Serum creatinine > 142 µmol/L (1.6 mg/dL) in female patients and > 168 µmol/L (1.9 mg/dL) in male patients and no active renal disease
3. ALT (SGPT) or AST (SGOT) = 3 ULN (If initial yield ALT or AST =3 ULN, a second sample may be taken and tested)
4. Platelet count < 100 x 10(9)/L (100,000/mm3)
5. Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
6. WBC < 1.0 x 10(9)/L (1000/mm3), ANC < 1 x 10(9)/L(1000/mm3)
7. Absolute lymphocyte count < 0.5 x 10(9)/L (500/mm3)
8. Known positive hepatitis B surface antigen or hepatitis C antibody
9. Total bilirubin > ULN (If initial sample yields bilirubin > ULN, a second sample may be taken and tested)
10. Triglycerides > 10 mmol/L (> 900 mg/dL) at inclusion in extension study

General medical:
11. Treatment with any investigational agent since the last administration of study drug in the MA21573 study
12. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20) since the last administration of study drug in the MA21573 study
13. Treatment with iv gamma globulin, plasmapheresis or Prosorba™ column since the last administration of study drug in the MA21573 study
14. Treatment with an anti-TNF or anti-IL1 agent, or a T-cell co-stimulation modulator or any biologic or participation in any research study since the last administration of study drug in the MA21573 study
15. Parenteral, intramuscular or intra-articular corticosteroids within 6 weeks since the last administration of study drug in the MA21573 study
16. Immunization with a live/attenuated vaccine since the last administration of study drug in the MA21573 study
17. Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation since the last administration of study drug in the MA21573 study
18. 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 intrauterine device (IUD)
19. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or GI disease
20. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
21. Current liver disease as determined by the investigator. Patients with prior history of ALT (SGPT) elevation are not excluded
22. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, 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 or oral antibiotics
23. History of or currently act

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)

Trade Name: RoActemra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: RO4877533
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: To assess the long-term safety and tolerability of TCZ monotherapy or in combination with non-biologic DMARDs in patients with RA and at least a moderate response to TCZ after 24 weeks of treatment.

Primary end point(s): Incidence of AEs and SAEs of TCZ monotherapy or combined treatment with TCZ and one or more of the background non-biologic DMARDs approved for RA in patients with moderate to severe active RA.

Secondary Objective: To assess the long-term efficacy of TCZ monotherapy or its combination with non-biologic DMARDs in patients with RA and at least a moderate response to TCZ after 24 weeks of treatment.

Secondary ID(s)

MA22460

2008-006924-68-ES