E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
early active Rheumatoid Arthritis, previously untreated with DMARDS |
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E.1.1.1 | Medical condition in easily understood language |
early active Rheumatoid Arthritis, previously untreated with DMARDS |
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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 | 20.0 |
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 study in patients with severe RA, the efficacy and effectiveness of a classic COBRA scheme (with 15mg MTX) versus two modified COBRA schemes respectively “slim” (without SSZ and with half dose steroids) and “avant-garde” (leflunomide instead of SSZ and half dose steroids) in daily practice.
To study in patients with less severe RA, the daily practice efficacy and effectiveness of a tight step up regimen (with 15mg MTX) versus a modified COBRA slim scheme (without SSZ and with half dose steroids).
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E.2.2 | Secondary objectives of the trial |
A superiority analysis will be performed: in the high risk arm, COBRA classic and COBRA avant-garde vs. COBRA slim and in the low risk arm, COBRA slim vs. Tight Step Up. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Genetic substudy.
Objectives:
- This genetic research can lead to better strategies for the treatment of RA. |
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E.3 | Principal inclusion criteria |
- Age ≥ 18 years
- Diagnosis of RA as defined by the 1987-revised ACR classification criteria or the new ACR/Eular 2010 criteria for early RA
- Early RA defined by a disease duration of ≤ 1 year
- Use of a reliable method of contraception for women of childbearing potential
- Able and willing to give written informed consent and participate in the study
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E.4 | Principal exclusion criteria |
- Previous treatment with methotrexate or leflunomide
- Previous treatment with cyclophosfamide, azathioprine or cyclosporine
- Previous treatment with sulphasalazine for more than 3 weeks
- Previous treatment with hydroxychloroquine for more than 6 weeks
- Previous treatment with corticoids or intra-articular glucocorticoïds within 4 weeks before treatment start or for more than 4 weeks
- Previous treatment with an investigational drug for the treatment/prevention of RA
- Contraindications for corticosteroids
- Contraindications for methotrexate, sulphasalazine or leflunomide
known chronic hepatic disease (alcoholic, fibrosis, …)
known pulmonary interstitial disease or fibrosis
known chronic renal failure
history of malignant neoplasm within 5 years
hematologic problems at the discretion of the investigator
- Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study
- Pregnancy, breastfeeding or no use of a reliable method of contraception
- Alcohol or drug abuse
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion in remission (DAS28CRP < 2.6) |
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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) |
Efficacy:
• Disease activity:
– Proportion good EULAR responders
– Proportion of patients in remission according to the SDAI
(score ≤ 3,3).
– Proportion of patients in remission according to the CDAI
(score ≤ 2 ,8).
– Proportion of patients in remission according to the preliminary
Boolean ACR/EULAR criteria.
– Proportion of patients in remission according to DAS28CRP
<2.4
• Functionality:
– Proportion CM HAQ responders (delta > 0,22)
– Proportion HAQ = 0
• X-ray (Sharp Vanderheijde score)
Effectiveness:
• Proportion of treatment failures due to efficacy/effectiveness problems
• Proportion with unplanned treatment changes (steroids and DMARDs)
• Proportion lost from follow up
• Total cumulative steroid dose / mean steroid dose per day
• Proportion started on biologics
Safety: number / type of (serious) adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 16 weeks, 52 weeks and 104 weeks |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
prospective study to compare different treatmentstrategies. |
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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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 16 |
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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end of trial is normally the last visit of the last subject, in case of safety concerns or major logistic problems the organizer of the trial can discontinue it, as described in the protocol |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |