E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
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 efficacy of extra dose of rituximab in patients selected on the basis of B cell analysis with resistant RA compared with placebo dose, following standard rituximab therapy.
|
|
E.2.2 | Secondary objectives of the trial |
i) to study the efficacy and safety of an extended course of rituximab in patients with resistant RA who have B CELLS following rituximab therapy ii) to study the utility of B CELLS as a marker to indicate whether patients will benefit from extended treatment with rituximab iii) to study the effects of rituximab on underlying structural joint disease and B cell profiles in the peripheral circulation
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with rheumatoid arthritis for at least 6 months, diagnosed according to the revised 1987 ACR criteria for the classification of rheumatoid arthritis
2. Patients who have experienced an inadequate response to previous or current treatment with etanercept, infliximab or adalimumab because of toxicity or inadequate efficiency or be unsuitable for treatment with anti-TNF therapy because of contra-indication
3. Patients must have received methotrexate at a dose of 10-25mg/week (po or parenteral) at a stable dose for 4 weeks prior to screening
4. DAS28 >5.1
5. Age 18-80 years
6. Corticosteroids (≤10mg/day prednisolone or equivalent) permitted if stable for at least 4 weeks prior to screening and NSAIDs permitted if stable for at least 2 weeks prior to screening.
7. Patients of reproductive potential (males and females) using a reliable means of contraception (eg contraceptive pill, IUD, physical barrier)
8. Presence of erosive joint disease of at least 1 joint on x-ray ( except if DIP joint of the hand)
|
|
E.4 | Principal exclusion criteria |
1. Bone/joint surgery within 8 weeks prior to therapy or joint surgery planned within 24 weeks of therapy
2. Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA
3. History of, or current, inflammatory joint disease other than RA or other systemic rheumatic disorder
4. Concurrent treatment with any DMARD (apart from methotrexate) or any anti-TNF therapy or other biologic agent
5. Treatment with any investigational agent within 4 weeks of screening or 5 half lives of the investigational drug
6. Previous treatment with any cell depleting therapy therapies.
7. Intra-articular or parenteral steroids within 4 weeks prior to therapy (except for joints undergoing ultrasound or MRI where IA steroids are not permitted within 12 weeks prior to therapy or assessment)
8. Previous treatment with Rituximab
9. History of severe allergic or anaphylactic reactions to humanised or murine monoclonal antibodies.
10. Evidence of significant uncontrolled concomitant diseases.
11. Known active bacterial, viral, fungal mycobacterial infection or any episode of infection requiring hospitalisation or treatment with iv antibiotics within 4 weeks of therapy or oral antibiotics within 2 weeks of therapy
12. History of, or currently active, primary or secondary immunodeficiency
13. History of solid organ malignancy in the past 5 years (excluding basal cell or squamous cell carcinomas of the skin which have been excised and cured)
14. Pregnant women or breastfeeding mothers
15. History of alcohol, drug or chemical abuse within 6 months prior to screening
16. Neuropathies or neurovasculopathies which might interfere with pain evaluation
17. Significant laboratory abnormalities. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with B CELLS receiving three doses of rituximab (Group A) vs proportion of patients with B CELLS who receive standard dose (two doses) rituximab (Group B) achieving ACR20 response at Week 28.
|
|
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 | Yes |
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 | Yes |
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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
intially open label with blinding for the placebo phase (final dose) |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Yes |
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
| |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |