E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active, severe and advanced axial ankylosing spondylitis |
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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 compare the efficacy of etanercept (50mg, once weekly) with that of placebo in adults with active, severe and advanced Ankylosis Spondylitis (as defined by the Modified New York criteria) at week 12. |
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E.2.2 | Secondary objectives of the trial |
To determine: - The efficacy of etanercept compared with that of placebo at weeks 2, 4, 8. - The efficacy of the original etanercept group from baseline to week 24 - The change in efficacy of the original placebo group from week 12 to week 24. (the efficacy of the original etanercept group will be analysed separately from the original placebo group even though both groups will be treated with etanercept for the 2nd 12 weeks). - The safety of etanercept in this patient population by analyzing safety data for all patients receiving at least one dose of test article. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of Ankylosing Spondylitis (AS), as defined by the Modified New York criteria. 2. Axial, defined by a score ≥ 30 for the overall level of AS neck, back or hip pain (on a 100 mm VAS) (question 2 of the BASDAI). 3. Refractory to standard anti-rheumatic treatment (at least 2 NSAIDs at maximum tolerated dose with duration > 3 months and according to the opinion of the investigator). 4. Active, defined by BASDAI ≥ 40 despite optimal NSAID treatment. 5. Advanced and severe, defined by the presence of 1 of the 3 following criteria : - 2 intervertebral adjacent bridges and/or fusion of the lumbar spine, - 3 intervertebral adjacent bridges and/or fusion of the dorsal spine, - 2 intervertebral adjacent bridges and/or fusion of the cervical spine. 6. Between 18 and 70 years of age. 7. Negative serum pregnancy test taken at screening in all women except those surgically sterile or at least 1 year post-menopausal. Sexually active women of childbearing potential participating in the study must use a medically acceptable form of contraception (which includes oral contraception, injectable or implantable methods, intrauterine devices, or properly used barrier contraception). A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who use contraceptives or whose sexual partners are either sterile or use contraceptives. 8. Agreement by male subjects who are not surgically sterile and female subjects who are not surgically sterile or post-menopausal to use of a reliable method of birth control for the duration of the study. 9. Ability to reconstitute and self-inject drug or have a designee who can do so. 10. Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific screening procedures are performed. 11. Ability to store injectable test article at 2°C-8°C. |
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E.4 | Principal exclusion criteria |
1. Previous receipt of etanercept or other TNFα inhibitors. 2. Use of disease modifying drugs other than hydroxychloroquine, sulphasalazine, and methotrexate within 4 weeks of baseline. Patients treated with hydroxychloroquine, sulphasalazine and methotrexate may continue these drugs during this study but doses must be held stable for 4 weeks before baseline examination and for the duration of the study. 3. Receipt of multiple NSAIDs at baseline. 4. Dose of NSAID changed within 2 weeks of baseline evaluation. 5. Dose of prednisone > 10mg/day (or equivalent) or changed within 2 weeks of baseline evaluation. 6. Abnormality in chemistry or haematologic profiles: white blood cell count ≤ 3.5 x 109/L; haemoglobin ≤ 85 g/L or 5.3 mmol/L; haematocrit ≤ 27%; platelet count ≤ 125 x 109/L; serum creatinine ≥ 175 μmol/L; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2 times the laboratory’s upper limit of normal. 7. Significant concurrent medical events : - Uncompensated congestive heart failure. - Diagnosis of multiple sclerosis or other central demyelinating diseases. - Presence or history of confirmed blood dyscrasias. - Cancer or history of cancer (other than resected cutaneous basal cell or squamous cell carcinoma). - Serious infection (infection association with hospitalization and/or intravenous antibiotics) within 1 month of test article administration or active infection at baseline. - Any condition that, in the physician’s judgment, might cause this study to be detrimental to the subject. - History of HIV+ or TB+ test (follow the local country guidelines for appropriate screening and treatment of tuberculosis in the setting of anti-TNF α therapy) 8. Known contraindication or hypersensitivity to etanercept or its excipients. 9. Pregnant or breast-feeding women. 10. History of poor compliance. 11. History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent. 12. History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements or give informed consent. 13. Receipt of any investigational drug or biological agent within 3 months of screening visit. 14. Employment by the investigator or reporting directly or indirectly to the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the normalized net incremental area under the curve (AUC) between randomization and week 12 for the BASDAI. |
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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 | 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 | 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 | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |