E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe plaque psoriasis |
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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 assess the efficacy and safety of etanercept 50 mg administered once weekly in subjects with psoriasis over 12 weeks. |
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E.2.2 | Secondary objectives of the trial |
to evaluate the quality of life, pharmacokinetics as well as the open-label safety and efficacy of etanercept administered once weekly for up to 24 weeks. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Adults ≥ 18 years of age with clinically stable plaque psoriasis involving ≥ 10% of the body surface and a minimum Psoriasis Area and Severity Index (PASI) score of 10 at screening. 2. Failure to respond to, or have a contraindication to, or intolerance to at least 1 of the following systemic or phototherapies at an adequate dose of sufficient duration: · Methotrexate (MTX) · Acitretin· Cyclosporine · Ultraviolet A (UVA)· Ultraviolet B (UVB)· Psoralen and ultraviolet A (PUVA)· Fumarate 3. Negative serum ß-human chorionic gonadotropin (ß-HCG) pregnancy test taken at screening or baseline for all women, except those who are surgically sterile or at least 1 year postmenopausal. 4. Sexually active women of childbearing potential and sexually active men participating in the study must use a medically acceptable form of contraception. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used barrier contraception. Additionally, the use of condoms is suggested as an adjunct to the methods previously addressed to protect against sexually transmitted diseases and to provide additional protection against accidental pregnancy. 5. Subject or designee must have the ability to reconstitute and inject test article subcutaneously. 6. Subject is capable of understanding and giving written, voluntary informed consent before study screening. 7. Ability to store injectable test article at 2°C to 8°C. |
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E.4 | Principal exclusion criteria |
1. Previous treatment with etanercept, antibody to TNFa, or other TNFa inhibitors. 2. Active guttate, erythrodermic, or pustular psoriasis at the time of the screening or baseline visit. 3. Serious infection (requiring parenteral antibiotic and/or hospitalization) within one month prior to screening or baseline visit. 4. Abnormality in hematology or chemistry profiles at screening or baseline visit: alanine transaminase (ALT) and aspartate transaminase (AST) ≥ 2 x the upper limit of normal: hemoglobin ≤ 85 g/L (8.5 g/dL); platelet count ≤ 125 x109/L (125,000 cells/mm3); white blood cell count ≤ 3.5 x109/L (3,500 cells/mm3); serum creatinine ≥ 177 µmol/L (2 mg/dL). 5. Evidence of skin conditions at the time of the screening or baseline visit (eg, eczema) that would interfere with evaluations of the effect of test article on psoriasis. 6. Receipt of any investigational drug(s) within 3 months of baseline visit. 7. Receipt of any live (attenuated) vaccine within one month prior to baseline visit. 8. Receipt of alefacept, efalizumab, anti-CD4 agents, and diphtheria IL-2 fusion protein 6 months prior to baseline visit. 9. PUVA, UVA, or UVB therapy one month prior to baseline visit. 10. Receipt of any systemic psoriasis therapy (including methotrexate) or oral or parenteral corticosteroids one month prior to baseline visit. 11. Topical steroids, topical vitamin A or D analog preparations or anthralin 2 weeks prior to baseline visit (exception – topical steroids at no higher than moderate strength are permitted on the scalp, axillae, groin, but dose and brand must be kept constant for the duration of part A). 12. Topical cyclosporine, pimecrolimus, and tacrolimus, or calcineurin inhibitors 2 weeks prior to baseline visit. 13. Body mass index > 38 (see attachment) 14. Pregnant or breast-feeding women. 15. Abnormal or clinically significant chest radiograph within 12 months of the screening visit. 16. Significant concurrent medical conditions at the time of screening or baseline including:· Presence of active infection or any underlying diseases that could predispose subjects to infections.· Uncontrolled hypertension (defined as screening systolic blood pressure measurement of greater than 180 mm Hg or screening diastolic blood pressure of greater than 110 mm Hg).· Myocardial infarction less than one year prior to baseline visit.· Unstable angina pectoris within 6 months of baseline visit.· Class III or IV congestive heart failure as defined by the New York Heart Association10(see attachment).· Severe pulmonary disease requiring hospitalization or supplemental oxygen therapy.· Diagnosis of multiple sclerosis or any other demyelinating disease.· Uncontrolled insulin-dependent diabetes mellitus.· Any rheumatologic disease such as rheumatoid arthritis, systemic lupus erythematous, systemic vasculitis, scleroderma, polymyositis, or associated syndromes.· Cancer or history of cancer (other than resected cutaneous basal cell or squamous cell carcinoma).· Open cutaneous ulcers.· Active tuberculosis (follow your country’s guidelines for appropriate screening and treatment of tuberculosis in the setting of anti-TNF therapy).· Known human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) positive.· Any condition that, in the judgment of the investigator, might cause this study to be detrimental to the subject. 17. Current or history of psychiatric disease that would interfere with the ability to comply with the study protocol or give informed consent. 18. History of alcohol or drug abuse that would interfere with the ability to comply with the study protocol. 19. 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 efficacy endpoint is the PASI 75 response at week 12. PASI 75 is defined as a 75% or greater improvement in PASI score from baseline.
The secondary efficacy endpoints will include but not limited to: · PASI 50 · PASI 75 (at visit other than week 12) · PASI 90 · PASI score · PGA of 0 or 1 (clear or minimal) · PGA of 0, 1, 2 (clear, minimal, mild) · PGA · Patient global assessment of Psoriasis · DLQI score · DLQI response (proportion of subjects with a DLQI score of 0 or with an improvement of greater than or equal 5 points from baseline) · FACIT-F response (proportion of subject with improvement of greater than or equal 3 points from baseline) · FACIT-F score· EQ-5D score |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 the study is the last visit (follow-up) of the last subject. |
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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 | 14 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 14 |