| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Psoriasis is an inflammatory skin disorder that affects between 1 and 2% of the population. It is characterised by an increased proliferation of the epidermis, and presents as well-defined thickened erythematous patches typically covered with a silver scale. | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10037153 | |
| 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 | | The primary objective is to assess the safety and efficacy of an initial 12-week treatment course with onercept 150 mg TIW for the induction of remission in patients with moderate to severe psoriasis, compared to matching placebo. | |
| E.2.2 | Secondary objectives of the trial | | The secondary objectives are to assess the safety of continued therapy with onercept for 28 weeks in patients having received an initial 12-week treatment course with onercept 150 mg TIW or placebo and to assess the safety and efficacy of withdrawal of therapy after 28-40 weeks continuous treatment by comparing onercept 150 mg TIW with matching placebo during a 12-week placebo controlled randomised withdrawal period. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | 1. Written informed consent, given before any study-related procedure not part of the subject’s normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care.
2. At least 18 years of age.
3. Female subjects must be neither pregnant nor breast-feeding, and must lack childbearing potential, as defined by either:·
Being post-menopausal (i.e. at least 12 months past last menses) or surgically sterile, or
Using an effective form of contraception (i.e. condoms, oral contraceptives or IUD).
Confirmation that the subject is not pregnant must be established by a negative urinary hCG test within 7 days before Study Day 1 (SD1). A pregnancy test is not required if the subject is post-menopausal or surgically sterile.
4. Outpatient status at the time of enrolment.
5. Plaque psoriasis for at least 12 months.
6. Plaque psoriasis covering at least 10% of total body surface area and a PASI score of 12.0 or more.
7. Candidacy for phototherapy or systemic therapy.
8. Static PGA of 3 or more. | |
| E.4 | Principal exclusion criteria | 1. Use of more than one NSAID to treat psoriatic arthritis or having a change in chronic NSAID regimen during the 28 days before SD1. Note for guidance: subjects with psoriatic arthritis who are not expected to be controlled by one stable NSAID regimen throughout the entire duration of the study should not be included.
Clarification: After SD1, use of short courses of NSAIDs or opioids (for less than 28 days) is allowed to treat adverse events.
2. No change. Same as in original application form.
3. Participation in any other investigational study or experimental therapeutic procedure that is considered to interfere with the study within 3 months before
SD 1.
Clarification: For investigational medicinal products, the 3-month period prior to SD 1 is calculated from the last dose received. This period can be reduced if the previous treatment is not considered to interfere with participation in this study, e.g. topical treatments for psoriasis and/or if time between last dose received is more than 5 times the half life of the IMP received. However, if the subject is still in the follow-up period of another study, participation in this study is not allowed.
4. No change. Same as in original application form.
5. Experimental or off-label treatments for psoriasis and/or psoriatic arthritis, such as azathioprine, hydroxyurea/hydroxycarbamide, mycophenolate, chlorambucil, leflunomide or cyclophosphamide, within 1 year prior to SD1.
6. Treatment with cyclosporin, methotrexate, oral retinoids retinoids (i.e acetretin), or fumaric acid esters within 28 days (3 months for acetretin) before SD 1.
7. Treatment with any topical therapies, such as vitamin D derivatives, corticosteroids, tars and tar oils, dithranol for chronic or short contact therapy, salicylic acid and topical retinoids, within 14 days before SD 1.
8. No change. Same as in original application form.
9. No change. Same as in original application form.
10. Abnormal liver function, defined by a total bilirubin ≥ 1.2 times the upper limit of normal values (except in case of Gilbert’s syndrome), or aspartate aminotransferase, alanine aminotransferase or total alkaline phosphatase levels ≥ 2.5 times the upper limit of normal values.
11. No change. Same as in original application form.
12. No change. Same as in original application form.
13. Seropositivity for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
Clarification: Subjects previously vaccinated for hepatitis B are allowed into this study. Testing for hepatitis B seropositivity as the eligibility criterion for this study is related to hepatitis B surface antigen (HBsAg) results.
14. No change. Same as in original application form.
15. History of cancer in the preceding 5 years (except adequately treated basal cell carcinoma of the skin or squamous cell carcinoma in situ of the skin). Any history of hematopoietic cancer.
16. History of active tuberculosis, current active tuberculosis or candidacy for prophylactic therapy for tuberculosis (see Appendix I for guidance on PPD testing, chest X-ray screening and evaluation of patients at high risk for tuberculosis).
17. No change. Same as in original application form.
18. History of any opportunistic infection (e.g., viral, fungal, protozoal, or bacterial) in the 6 months preceding SD1 related to any clinical condition of immunodeficiency.
19. No change. Same as in original application form.
20. No change. Same as in original application form.
21. No change. Same as in original application form.
22. Requirement for immunisation, allergy desensitisation or vaccination during the entire study period (it is recommended that these procedures be scheduled at least 14 days prior to SD 1 or >3 months after the last injection of study drug), with the exception of killed influenza vaccines which are allowed at any time during the study.
23. No change. Same as in original application form.
24. No change. Same as in original application form.
25. No change. Same as in original application form.
26. Live or killed virus or bacteria vaccines within 14 days before SD 1, with the exception of killed influenza vaccines which are allowed prior to SD 1 and at any time during the study.
27. Bedridden status.
28. No change. Same as in original application form. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary endpoint is the proportion of subjects with at least a 75% improvement in the Psoriatic Area and Severity Index (PASI) score between baseline (Study Day 1) and week 12 of the First Treatment period (PT). | |
| 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 | 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| 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 | |
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 6 |
