E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spondyloarthropaties and ankylosing spondyllitis |
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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 the effect of discontinuation of TNF-alpha inhibitor therapy in patients with spondyloarthritis (SpA) with low disease activity after at least 1 year of treatment with respect to clinical disease flare (as assessed by Kaplan-Meier statistics). To investigate the efficacy of TNF-alpha inhibitor when re-starting therapy because of disease flare in the above mentioned patient population. |
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of discontinuation of TNF-alpha inhibitor therapy with respect to disease flare as assessed by MRI (as measured by Kaplan-Meier statistics) To investigate the effect (as measured by conventional and experimental imaging and laboratory methods) of discontinuation of TNF-alpha inhibitor. To identify candidate imaging- and bio- markers for prediction of flare in SpA patients discontinuing TNF-alpha inhibitor. To identify candidate imaging- and bio- markers for improved assessment of disease activity and progression in SpA patients discontinuing and eventually re-starting TNF-alpha inhibitor. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. At least 12 months of treatment with a) adalimumab 40 mg subcutaneously every other week, or b) subcutneous injection of Etanercept 25 mg twice weekly or Etanercept 50 mg once a week or c) infusion of Infliximab 3 mg/kg or 5 mg/kg every 6 to 8 week 2. Diagnosis of spondylarthritis according to the European Spondyloarthritis Study Group (ESSG) criteria (Dougados et al, Arthritis Rheum 1991; 34: 1218-27) or ankylosing spondylitis according to the modified New York Criteria 3. No clinical active disease, defined as a BASDAI score < 4 (equal to 40 mm on a 100 mm Visual Analogue Scale) on 2 consecutive timepoints with at least 3 months between 4. An X-ray or MRI made before initiation of TNF-alpha inhibitor that showed features confirming previous sacroiliitis, or active inflammatory changes on MRI 5. Among other issues: Age >18 years, able to give informed consent, no contraindications for anti-TNFa-therapy |
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E.4 | Principal exclusion criteria |
1. Treatment with disease modifying anti-rheumatic drugs (DMARDs) are accepted during the study, but no changes in the dose is allowed. 2. Oral, intraarticular, intramuscular or intravenous glukokorticoid within 4 weeks before screening 3. Pregnancy or lactation - patients who wants to get pregnant (male or female) can take part in the first 6 months of the study, because they have to use sufficient contraceptives in 6 moths after withdrawal of TNF-alpha inhibitors 4. HIV, hepatitis B or C, tuberculosis, other infections 5. Malignancies 6. Other serious concomitant diseases (uncontrolled/severekidney, liver, haematological, gastrointestinal, endocrine, cardiovascular, pulmonary, neurological ore cerebral disease (including demyelinating disease) 7. Contraindications to anti-TNFa-therapy 8. Contraindications to MRI |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is disease flare defined as a change in BASDAI of 2 points (or 20 mm on a VAS scale). For patients with disease flare re-starting adalimumab there is a secondary endpoint: ASAS50% response 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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | 13 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |