E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 whether Etanercept 25mg once weekly is effective in maintaining a clinical response in patients with ankylosing spondylitis who have responded to 50mg once weekly.
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E.2.2 | Secondary objectives of the trial |
To assess additional measurements of efficacy and adverse effects in low and high dose groups.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
At screening / baseline The participant will be placed on Etanercept 50mg once weekly providing: a) Diagnosis of AS according to the modified New York criteria (Study Protocol, Appendix 1). b) Confirmation of sustained active spinal disease, demonstrated by: i. BASDAI score of at least 4 units (Study Protocol, Section 5.6) ii. At least 4 cm on a 0-10cm spinal pain visual analogue scale (VAS) iii. Both severity measures demonstrated on two occasions at least 12 weeks apart without any change of treatment c) Conventional treatment with two or more NSAIDs taken sequentially at maximum tolerated or recommended dosage for 4 weeks have failed to control symptoms. d) Participant has clinically acceptable results from laboratory screening test. e) Male or Female, aged 18 – 80 years f) Participant is willing and able to give informed consent to participate in the study. g) Able (in the Investigators opinion) and willing to comply with all study requirements.
At randomisation The participant will be randomised to 50mg or 25mg Etanercept providing: a) An adequate response to treatment has been achieved, with response defined as: i. reduction of the BASDAI score to 50% of the pre-treatment value OR ii. reduction in BASDAI by 2 or more units AND iii. reduction of the spinal pain VAS by 2 cm or more. b) The participant finds Etanercept acceptable and wishes to continue treatment
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E.4 | Principal exclusion criteria |
At screening / baseline: the participant will not enter the study if ANY of the following apply: a) Previous treatment with any licensed or experimental anti TNF therapy. b) Chronic infection of the upper respiratory tract (e.g. sinusitis), chest (e.g. bronchiectatic lung disease), urinary tract or skin (e.g. paronychia, chronic ulcers, open wounds). c) Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. d) Any ongoing or active infection or any major episode of infection requiring hospitalisation or treatment with intravenous (IV) antibiotics within the preceding 30 days and/or orally administered antibiotics in the preceding 15 days. e) Received any live (attenuated) vaccines within four weeks of screening visit. f) Known immunosuppressive disease or treatment with immunosuppressive drugs. g) Active / latent tuberculosis as identified by local screening guidelines. h) Stable corticosteroid use ≥10mgs OD taken in the 4 weeks prior to screening. i) History of hepatitis B or C. j) Significant concurrent cardio-vascular disease including; uncompensated congestive heart failure, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension. k) Cancer or a history of cancer (other than resected cutaneous basal cell carcinoma, and in situ cervical cancer) within five years of entering the screening period. l) Significant renal or hepatic impairment. m) Leukopaenia (wbc <3000 x 10^6/L) and/or neutropeania (wbc ≥1500 x 10^6/L). n) Thrombocytopaenia (platelets less than 150 x 10^9/L). o) Demyelinating disorders such as multiple sclerosis. p) Women who are pregnant, lactating or of childbearing potential not using contraception. q) Scheduled elective surgery/procedures requiring general anaesthesia during the study. r) Allergy to latex (the needle cover of the syringe contains latex). s) Presence of any other significant and uncontrolled medical condition, which in the investigator's opinion precludes the use of Etanercept t) Unable to give informed consent u) Unable/unwilling to comply with study procedures. v) Not available for follow-up assessments w) Received treatment with an investigational drug within 12 weeks prior to study screening. x) History of back injury or trauma which confounds the clinical scenario
At randomisation: the participant will not be randomised if ANY of the following apply: a) An adequate response to Etanercept 50mg per week has not been achieved by the end of the 6 month lead in period. b) The participant wishes to discontinue treatment with Etanercept. c) On the basis of adverse reactions, the treating physician considers the participant should withdraw from treatment with Etanercept.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome measure will be: • 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) AND/OR • Fall in BASDAI by >/= 2 units.
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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 | No |
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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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 |
Enbrel 50mg solution for injection in prefilled syringe (etanercept) - EU/1/99/126/015-18 |
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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 | 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
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The end of trial is defined in the study protocol as the date of the last follow up 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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |