Secukinumab Dosage Optimisation in Partial Responders With Moderate to Severe Plaque-type Psoriasis

Inclusion Criteria

Subjects eligible for inclusion in this study must fulfill all of the following criteria:

• Subjects must be able to understand and communicate with the investigator and must give a written, signed and dated informed consent before any study related activity is performed and who are willing and capable to comply with all study procedures.
• Men or women at least 18 years of age at time of screening.
• Chronic plaque type psoriasis diagnosed for at least 6 months prior to baseline
• Moderate to severe plaque type psoriasis at baseline derived from the European consensus (Mrowietz et al., 2011): BSA (Body Surface Area) >10% and PASI>10 and DLQI>10.
• Candidates for biologic therapy who failed to respond to, or who had a contraindication to or were intolerant to previous conventional systemic therapies.
• According to local guidelines, to exclude chest infection before initiation of a biologic immunomodulating therapy, it is necessary to have obtained an image of the chest (X-ray, computerized tomography or magnetic resonance imaging) within 12 weeks prior to screening and have this evaluated by a qualified physician.

Exclusion Criteria

• Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttata psoriasis).
• Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium).
• Ongoing use of prohibited psoriasis and non-psoriasis treatments. Washout periods have to be adhered to.
• Subjects not willing to limit UV light exposure (e.g., sunbathing and/or the use of tanning devices) during the course of the study.
• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
• Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting IL-17A or the IL-17A receptor (e.g. brodalumab, ixekizumab).
• History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
• Study personnel or first degree relatives of investigator(s) must not be included in the study.
• Women who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)) who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception (Pearl Index 40 mIU/m or 6 weeks post- surgical bilateral oophorectomy with or without hysterectomy

**examples of particularly reliable methods with Pearl Index (PI) <1, according to guidelines of Deutsche Gesellschaft für Gynakologie und Geburtshilfe:

• hormonal oral contraception (Combination of estrogen and gestagen, PI=0.1-0.9) hormonal vaginal ring (combination of estrogen and gestagen, PI=0.65 uncorr.; 0.4 corr.)
• hormonal transdermal patch (combination of estrogen and gestagen, PI= 0.72 uncorr.; 0.9 corr.)
• Estrogen-free ovulation inhibitors containing desogestrel (PI=0.14)
• Implanted hormones containing etonogestrel (PI=0-0.08)
• Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.)
• Intra-uterine progestine device (synthetic progestin containing IUDs,PI=0.16)
• Oral contraceptives without estrogen (e.g. "mini-pills"), nonsynthetic progesterone only IUDs, female condoms, cervical shield, periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy. Patients with psoriatic arthritis are not excluded.
• Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places t