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 | PT |
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 compare the efficacy of Rituximab re-treatment according to different initial response rates |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that re-treatment with Rituximab in rheumatoid arthritis is safe |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with active rheumatoid arthritis (DAS28 >=2.6) who participated in ML19070 (FIRST trial) and have completed the week 24 visit and who experienced a decrease (between week 16 and 24 in study ML19070) in DAS28 > 0.6 2.Eligible for re-treatment by the following criteria: Swollen joint count >=2 Tender joint count >=2 3. Not more than 1 year have passed since the patient’s first rituximab infusion within study ML19070 4. Not more than one TNF-alpha- inhibitor in history 5.Willingness and capability to give written informed consent, and willingness to participate and to comply with the study 6. Age range: 18 – 80 years at inclusion date in ML19070 7. Pregnancy urine test at screening (not earlier than 28 days prior to day 1)
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E.4 | Principal exclusion criteria |
General exclusion criteria 1. Patients from ML19070 having received any DMARD except MTX, any TNFalpha inhibitor, leflunomide or any anti-IL or CTLA4 Ig or any biological or investigational agent after the rituximab infusions 2. Patients with a response between week 16 and 24 in study ML19070 in DAS28 <=0.6 to rituximab. These Patients will remain in study ML19070 until completion or withdrawal.
Exclusion criteria related to RA 3. Functional class IV
Exclusion criteria related to general health 4. Patients with other chronic inflammatory articular disease or systemic autoimmune disease 5. Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms 6. Primary or secondary immunodeficiency 7. History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised 8. Evidence of significant uncontrolled concomitant diseases or serious and/or uncon-trolled diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome 9. Neuropathy that can interfere with filling out the patient's questionnaires 10. History of a severe psychological illness or condition 11. Known hypersensitivity to any component of the product or to murine proteins 12. Women lactating, pregnant or of childbearing po¬tential and males of reproductive potential not using a highly effective contraceptive method (i.e. with a failure rate of less than 1% per year, are implants, injectables, com-bined oral contraceptives, IUDs (only hor-mon¬spirals), sexual abstinence or vasecto¬mi¬zed partner. Women of childbearing potential must have a negative pregnancy test (urine) at screening and must confirm in a written form at day 1, day x2, and day x3 that they are not pregnant if the pregnancy test is not repeated. 13. History of alcohol, drug or chemical abuse 14. Lack of peripheral venous access
Exclusion criteria related to medications 15. Intolerance to rituximab 16. Previous treatment with abatacept 17. Treatment with corticosteroids exceeding 10 mg per day prednisone or equivalent 2 weeks prior to day 1 18. Patients who have developed known contraindications to high dose corticosteroids (e.g. poorly controlled hypertension or diabetes mellitus, history of psychological events to steroids). 19. Intolerance or contraindication to drugs required for the treatment of the side effects of rituximab 20. Receipt of a live vaccine within 4 weeks prior to treatment 21. Intra- articular or parenteral corticosteroids within 4 weeks prior to treatment
Exclusion criteria related to lab findings 22. Haemoglobin < 8.5 g/dl 23. Neutrophil counts < 1.500/µl 24. Platelet count < 75.000/µl 25. Serum creatinine > 1.4 mg/dl for women or 1.6 mg/dl for men 26. AST or ALT > 2.5 times upper limit of nor-mal 27. Positive HIV or hepatitis C serology as well as positive tests for hepatitis B surface antigen (HBsAg) and/or positive tests for hepatitis B core antibody (anti-HBc-Ab)
Exclusion criteria related to formal aspects 28. Previous (last 30 days) or current participation in another clinical trial with the exception of participation in study ML19070 29. Patients who have participated in this study before. 30. Patients who are underage or patients who are in¬capable to understand the aim, importance and consequences of the study and to give le-gal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 und Abs. 3 AMG). 31. Patients who possibly are dependent on the sponsor or investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change of DAS28 achieved by first re-treatment at week 24 Change from course specific baseline and original course baseline
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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 | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 72 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |