E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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 active primary or secondary immunodeficiency 24. Evidence of active malignant disease, malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors, except non-melanoma skin cancer that has been excised and cured), or breast cancer diagnosed within the previous 5 years 25. Human immunodeficiency virus (HIV) positive patients 26. History of alcohol, drug or chemical abuse within the 24-week MA21573 core study 27. Neuropathies or other painful conditions that might interfere with pain evaluation 28. Patients with lack of peripheral venous access
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 175 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |