NCT01961609

Methods	RCT, active‐controlled, double‐blind trial (SIGNATURE) Date of study: October 2013‐July 2016 Location: UK
Participants	Randomised: 230 participants Inclusion criteria Chronic plaque‐type psoriasis diagnosed for ≥ 6 months prior to screening, aged ≥ 18 years at screening Moderate‐severe disease severity: PASI ≥ 10 and DLQI > 10 Failed to respond to systemic therapies including ciclosporin and/or methotrexate and/or PUVA (or is intolerant and/or has a contraindication to these) Previously treated with ≥ 1 anti‐TNFα for moderate or severe psoriasis but is a primary or secondary non‐responder Exclusion criteria Forms of psoriasis other than chronic plaque‐type (e.g. pustular, erythrodermic and guttate psoriasis) Drug‐induced psoriasis (i.e. new onset or current exacerbation from beta‐blockers, calcium channel inhibitors or lithium) Ongoing use of prohibited psoriasis treatments (e.g. topical or systemic corticosteroids (CS), UV therapy). Washout periods detailed in the protocol must be adhered to. Ongoing use of other non‐psoriasis prohibited treatments. Washout periods detailed in the protocol have to be adhered to. All other prior non‐psoriasis concomitant treatments must be on a stable dose for ≥ 4 weeks before initiation of study drug. Previous exposure to secukinumab or any other biologic drug directly targeting IL‐17 or the IL‐17 receptor Pregnant or nursing (lactating) women, where pregnancy is 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) Women of childbearing potential, defined as all women physiologically capable of becoming pregnant unless they use 2 effective forms of contraception during the study and for 16 weeks after stopping treatment Men with a female partner of childbearing potential defined as all women physiologically capable of becoming pregnant unless they use 1 effective form of contraception during the study and for 16 weeks after stopping treatment Active systemic infections during the last 2 weeks (exception: common cold) prior to initiation of study drug and any infections that recur on a regular basis; investigator discretion should be used regarding patients who have travelled or recently resided in areas of endemic mycoses, such as histoplasmosis, coccidioidomycosis or blastomycosis and for patients with underlying conditions that may predispose them to infection, such as advanced or poorly controlled diabetes History of an ongoing, chronic or recurrent infectious disease, or evidence of TB infection as defined by a positive QuantiFERON TB‐Gold test (QFT) at screening. Patients with a positive QFT test may participate in the study if further work up establishes conclusively that the patient has no evidence of active TB. If presence of latent TB is established, then treatment must have been initiated and maintained according to UK guidelines Known infection with HIV, hepatitis B or hepatitis C at screening or at initiation of study drug
Interventions	Intervention Biological: secukinumab 150 mg at day 0 (initiation of study drug) and at weeks 1, 2, 3 & 4 Control Intervention Biological: secukinumab 300 mg at day 0 (initiation of study drug) and at weeks 1, 2, 3 & 4
Outcomes	At 16 weeks Primary outcome PASI 75 Secondary outcomes PASI 90 and PASI 75 after 2, 4, 8, 12, 24, 48 and 72 weeks Quality of life at 16 weeks
Notes	On www.clinicaltrials.gov Study completion date: July 2016 Ongoing study