E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
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 investigate whether a reduced-dose dosing regimen (1x500mg semiannually) of rituximab (RTX) (Mabthera®) is non-inferior in patients with rheumatoid arthritis (RA) whose disease is in persistent low disease activity (LDA) or clinical remission (REM) (pLDA/pREM) as compared to the standard dosing regimen of 1x1000mg semi-annual infusions. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of RA according to the 2010 ACR/EULAR classification criteria • Current treatment with RTX (at time of inclusion have already received at least 2 cycles of 1000mg RTX) at the Day-Clinic of the Division of Rheumatology of the Medical University of Vienna • Persistent low disease activity or clinical remission. Persistent clinical remission (pREM) will be defined as a simplified disease activity index (CDAI) ≤2.8 measured at two time-points 6 months apart. The CDAI is calculated as follows: TJC + SJC + GH + EGH (EGH=evaluator's assessment of general health on a 100 mm VAS, GH=patient's assessment of general health on a 100 mm VAS, SJC=28 swollen joint count, TJC=28 tender joint count). • Persistent low disease activity (pLDA) will be defined as a CDAI ≤10 measured at two timepoints 6 months apart • Patients who achieve REM at only either one of the two successive time-points will be considered as having pLDA with regard to the current trial |
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E.4 | Principal exclusion criteria |
• Patients ≤ 18 yrs • Patients receiving RTX for a disease other than RA • Patients who fail to meet criteria for REM or LDA at either one of the two successive timepoints (i.e. having a disease activity >10 as measured by the CDAI |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end points will be the proportions of flares in both groups evaluated by the disease activity score 28 (DAS28). Disease flare will be defined as a change in DAS28 of >1.2 or an increase in DAS28 of 0.6-1.2 if this results in DAS28 >3.2 ("reverse" EULAR improvement criteria). DAS28 is defined as follows: 0.56 * sqrt(TJC) + 0.28 *sqrt(SJC) + 0.70*ln(ESR) + 0.014*GH. ESR=erythrocyte sedimentation rate. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
months 3, 6, 9, 12, 15, 18, 21, 24 |
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E.5.2 | Secondary end point(s) |
Secondary outcome measures will include radiographic progression as measured by change in the Sharp modified van der Heijde (SvdH) score on standard radiographs, as well as physical function, as measured by the health assessment questionnaire disability index (HAQ-DI). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |