E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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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 evaluate the response to etanercept treatment in TNF-alpha blockade naïve patients and patients who failed prior other anti-TNF-alpha treatment and to understand the mechanisms underlying the clinical response to TNF-alpha blockade. |
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E.2.2 | Secondary objectives of the trial |
1) What factors distinguish responding patients from non responding patients on etanercept treatment? Differences in cytokine profiles or other serological markers, RA activity driven by other mediators than TNF-alpha )
2) What percentage of patients (TNF-alpha blockade naïve versus failures on prior anti-TNF-alpha treatment) respond after 16 weeks of etanercept treatment?
3) What is the clinical efficacy of etanercept after 1 year treatment? (Eular response criteria (DAS 28), ACR response, RADAI, SF 36, HAQ, and radiological progession) 4) Can we find genetic markers, e.g. genetic polymorphisms in the TNF-alpha genes, that may predict diagnosis, efficacy and side-effects of treatment in the individual patient?
5) Can periferal blood (mRNA) micro-array analysis identify new markers that distinguish responders from non-responders to etanercept treatment?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients with the diagnosis rheumatoid arthritis according to the American Rheumatism Association (ARA) 1987 criteria and in ACR 1991 functional classes I, II, and III (see appendix) 2) The patient is naïve for anti-TNF-alpha therapy or has failed other prior TNF-alpha blockers 3) DAS 28 higher and/or equal to 3.2 4) Failure on two previously used DMARDs 5) Age > 18 and < 85 years old 6) Use concurrent methotrexate treatment (5 - 30 mg/week; stable since at least 28 days before initiation) during the study. Subjects may be taking nonsteroidal anti-inflammatory drugs, provided the dose and frequency have been stable for at least 28 days. Subjects may be receiving prednisone therapy < or equal to 10 mg/day provided that the dosage has been stable for at least 28 days prior to entry.
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E.4 | Principal exclusion criteria |
1) Pregnancy 2) Breastfeeding 3) A history of or current acute inflammatory joint disease of different origin e.g. mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter’s syndrome, systemic lupus erythematosus or any arthritis with onset prior to age 16 years 4) Acute major trauma 5) Therapy within the previous 60 days with: any experimental drug alkylating agents, e.g. cyclophosphamide, chlorambucil antimetabolites monoclonal antibodies (including infliximab and etanercept) growth factors other cytokines 6) Therapy within the previous 28 days with: parenteral or intraarticular corticoid injections oral corticosteroid therapy exceeding a prednisone equivalent of 10 mg daily present use of DMARDs other than methotrexate 7) Receipt of any live (attenuated) vaccines within 4 weeks prior to baseline 8) Fever (orally measured > 38 °C), chronic infections or infections requiring anti- microbial therapy 9) Other active medical conditions such as inflammatory bowel disease, bleeding diathesis, or severe unstable diabetes mellitus 10) Manifest cardiac failure (stage III or IV according to NYHA classification) 11) Progressive fatal disease/terminal illness 12) a history of lymphoproliferative disease or treatment with total lymphoid irradiation. 13) A white cell count less than 3.5 x 109/l 14) Platelet count less than 100 x 109/l 15) Haemoglobin of less than 5.3 mmol/l 16) Body weight of less than 45 kg 17) History of drug or alcohol abuse 18) Any concomitant medical condition which would in the investigator’s opinion compromise the patient’s ability to tolerate, absorb, metabolize or excrete the study medication. 19) Inability to give informed consent 20) Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the percentage of patients with a moderate to good response to etanercept treatment at 16 weeks according to the Eular response criteria which is also applied in routine rheumatological practice. |
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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 | No |
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 | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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Provided in the protocol on page 18 |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
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 |