E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult Rheumatoid Arthritis (RA) |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 efficacy of treatment with tocilizumab (TCZ) 8 mg/kg intravenously (iv) (every 4 weeks) versus adalimumab (ADA) 40 mg subcutaneously (sc) (every 2 weeks), both in combination with methotrexate (MTX), with regard to achievement of clinical remission as measured by Disease Activity Score 28 (DAS28) <2.6 at the end of 24 weeks of treatment in patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate efficacy response to treatment with only one tumor necrosis factor (TNF) inhibitor (other than ADA). |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of TCZ and ADA by assessing:
• Efficacy parameters at week 24 by using American College of Rheumatology (ACR) criteria, European League Against Rheumatism (EULAR) criteria, low disease activity scores, patient-reported health assessments (Health Assessment Questionnaire [HAQ], Functional Assessment of Chronic Illness Therapy- Fatigue questionnaire [FACIT-Fatigue Scale], Short Form-36 [SF-36], Routine Assessment of Patient Index
Data [RAPID3]).
• Change of haemoglobin levels at week 24 vs baseline.
• Safety throughout the study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients, >/= 18 years of age
- Rheumatoid arthritis of >/= 6 months duration (according to ACR criteria)
- Inadequate response due to inefficacy of treatment (at least 3 months) with only one approved TNF-agent other than adalimumab. Depending on the TNF-inhibitor, last dose of TNF-inhibitor should have been 1 to 8 weeks before randomization to the study
- On methotrexate treatment for >/=12 weeks immediately prior to baseline, with stable dose (10-25 mg/week) for the last 8 weeks
- Disease Activity Score (DAS28) >3.2 at baseline
- Oral corticosteroids (</=10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs) are permitted if the dose has been stable for >/=6 weeks prior to baseline |
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E.4 | Principal exclusion criteria |
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
- Rheumatic autoimmune disease other than rheumatoid arthritis
- Prior history of or current inflammatory joint disease other than rheumatoid arthritis
- Functional class IV (ACR criteria)
- History of severe allergic reaction to human, humanized or murine monoclonal antibodies
- Known active current or history of recurrent infection (including TB)
- Primary or secondary immunodeficiency (history of or currently active)
- Body weight >150 kg
- Previous treatment with any cell-depleting therapies
- Previous treatment with tocilizumab
- Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical remission defined as DAS28<2.6 at week 24.
As a result of early termination of the recruitment prior to the completion of planned enrollment, the power/precision for the tests originally planned will not be sufficient. Therefore, revisions are necessary and will be specified in the SAP and noted in the final clinical study report. Descriptive statistics and/or patient listings will be prepared. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Proportion of patients with ACR20, ACR50 and ACR70 responses.
• Change from baseline in DAS28.
• Proportion of patients classified as categorical DAS28 responders (EULAR moderate and good response).
• Proportion of patients who achieve low disease activity defined as DAS28<3.2.
• Change from baseline in hemoglobin.
• Change from baseline in FACIT-Fatigue scores.
• Change from baseline in ACR core set (includes SJC, TJC, Patient Pain VAS, Patient Global VAS, Physician Global VAS, HAQ-DI, and acute phase reactants [hsCRP or ESR]).
• Change from baseline of RAPID3 score.
• Change from baseline in SF-36 scores (8 domain scores and physical and mental component summary measures [PCS and MCS, respectively]) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 66 |
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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The end of the study will occur when the last patient, last visit occurs (LPLV). The LPLV is either the date of the last patient visit of the last patient to complete the study, or the date at which the last data point from the last patient, which is required for statistical analysis (i.e., key safety and efficacy results for decision making), is received, whichever is the later date. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |