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 | 8.1 |
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 in rheumatoid arthritis after inadequate response to a single TNF-alpha inhibitors |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that 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 |
•Age 18 to 80 •Active rheumatoid arthritis (DAS 28 ≥3.2) •SJC ≥4 at screening and baseline •TJC ≥4 at screening and baseline •Patients with rheumatoid arthritis for at least 6 month diagnosed according to the revised 1987 ACR criteria for the classification of rheumatoid arthritis •Not more than one TNFα- inhibitor in history •Inadequate response to either etanercept (Enbrel) or infliximab (Remicade) or adalimumab (Humira). Inadequate response is defined as either a lack of response to the respective drug or loss of response to the respective drug or intolerance to the respective drug. Etanercept treatment must have been stopped at least 4 weeks prior to first rituximab infusion, treatment with infliximab or adalimumab at least 8 weeks prior to first rituximab in-fusion. •Willingness and capability to give written informed consent, written consent for data protection (legal requirement in Germany: datenschutzrechtliche Einwilligung) and willingness to participate and to comply with the study.
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E.4 | Principal exclusion criteria |
Exclusion criteria related to RA •Functional class IV as defined by the ACR classification of Functional Status in Rheuma-toid Arthritis. Exclusion criteria related to general health conditions •Patients with other chronic inflammatory articular disease or systemic autoimmune dis-ease, e.g. Systemic lupus erythematosus, Sjögren’s syndrome, active rheumatoid vascu-litis, a history of systemic diseases associated with arthritis, chronic fatigue syndrome •Any active infection, a history of recurrent clinically significant infection, a history of re-current bacterial infections with encapsulated organisms •Primary or secondary immunodeficiency •History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised •Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome •Neuropathy that can interfere with quality of life and/or pain assessment. •Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study. •Known hypersensitivity to any component of the product or to murine proteins. •Women, pregnant, nursing or of childbearing potential with a positive pregnancy test (urine test) •Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, IUD, physical barrier) for up to 12.5 months after first infusion of ri-tuximab •History of alcohol, drug or chemical abuse within 6 month prior to screening •Lack of peripheral venous access Exclusion criteria related to medications •Previous treatment with rituximab or intolerance to rituximab •Previous treatment with abatacept •Corticosteroids at doses exceeding 10 mg per day of prednisolone or the equivalent within the last 2 weeks prior to the first rituximab infusion or corticosteroids at instable doses within the last 2 weeks prior to the first rituximab infusion •Intolerance or contraindication to drugs required for the treatment of the side effects of ri-tuximab (e.g. paracetamol, acetaminophen, diphenhydramine, p.o. and i.v. corticosteroids, anti-emetics or H1 blockers) •Concurrent treatment with any DMARD (apart from MTX), any TNFalpha inhibitor, or any anti-IL or CTLA4 Ig or other biologic or any investigational agent •Receipt of a live vaccine within 4 weeks prior to treatment •Intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit Exclusion criteria related to lab findings •Haemoglobin < 8.5 g/dl •Neutrophil counts < 1.500 / µl •Platelet count < 75.000 / µl •Lower than 1 x 700/µl lymphopenia for more than three months prior to inclusion. •Serum creatinine > 1.4 mg/dl for women or 1.6 mg/dl for men. •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times upper limit of normal. •Positive HIV or hepatitis C serology as well as positive tests for hepatitis B surface antigen (HBsAg) and/or positive tests for hapatitis B core antibody (HbcAb)). Exclusion criteria related to formal aspects. •Patients who have paritcipated in this study before. •Patients who participate currently in another clinical trial or patients who participated in another clinical trial during the last 30 days. •Patients who are underage or patients who are incapable to understand the aim, impor-tance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 und Abs. 3 AMG). •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 at week 24 |
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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 | 73 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |