A 52-week, multicenter, randomized, double-blind study of subcutaneous secukinumab to demonstrate efficacy as assessed by Psoriasis Area and Severity Index at 16 weeks of treatment compared to ustekinumab and to assess long-term safety, tolerability and efficacy in subjects with
moderate to severe plaque psoriasis (CAIN457A2317)

Plaque psoriasis (psoriasis vulgaris) is the most frequent clinical
presentation of psoriasis. Psoriasis is a chronic disease with often a severe
impact on the quality of life.
The classic treatment is topical treatment with creams, ointments etc. (e.g.
corticosteroids), UV light therapy and systemic treatments like methotrexate
and cyclosporin. Treatment options have increased with the arrival of
biological treatments (especially TNF*-inhibitors, such as adalimumab,
etanercept and infliximab), but the place of these newer treatments must be
investigated. The existing biological have the disadvantage of relatively
frequent administration (adalimumab en etanercept, subcutaneously) or of
intravenous administration (infliximab). The percentage of patients with an
inadequate response to TNF*-inhibitors can be as high as 40-60%.
The arrival of a new class of systemic, biological drugs such as ustekinumab
(interleukin (IL)-12/23 inhibitor) has provided more treatment options.
Ustekinumab has shown good clinical efficacy. PASI response rates were better
than those of etanercept and comparable to PASI response rates of infliximab
and efficacy was generally maintained up to 3 years after initiation of
treatment.
Secukinumab is a recombinant high-affinity fully human monoclonal anti-human
Interleukin-17A antibody of the IgG1/*-class. Secukinumab binds to human IL-17A
and neutralizes the bioactivity of this cytokine. IL-17A is pivotal in several
autoimmune and inflammatory processes. Its neutralization is expected to treat
the underlying pathophysiology of immune mediated disease, and as a consequence
provide relief of psoriatic symptoms.
This study aims to provide additional data on the use of secukinumab for
moderate to severe psoriasis in comparison with ustekinumab.

Primary: To demonstrate the superiority of secukinumab in subjects with
moderate to severe plaque psoriasis based on the proportion of PASI 90
responders at Week 16, compared to ustekinumab.
Secondary: To demonstrate the superiority of secukinumab in week 52 in PASI 90
and onset of effect (proportion of subjects achieving PASI 75 at Week 4).
Safety and tolerability.

Multicenter randomized double-blind phase III parallel-group study.
Randomization (1:1) to:
* Secukinumab 300 mg (s.c. injections every 4 weeks) *)
* Ustekinumab 45 or 90 (depending on body weight) mg s.c. (s.c. injections
every 12 weeks).
*) after loading period of 4 week with weekly injections.
Secukinumab injections contain 150 mg of active drug. Therefore 2 injections
with active drug will be given every 4 weeks.
Ustekinumab injections contain 45 mg of active drug. Therefore both 12 weekly
injections may contain active drug (ustekinumab 90 mg) or one may contain
active drug and one placebo (ustekinumab 45 mg).
Placebo injections (2 per occasion) will be used for the ustekinumab group at 4
and 8 weeks after the last active dose.
Screening period of max. 4 weeks. Treatment period approx. 1 year. Follow-up 4
weeks.
Evaluation of efficacy at week 16.
Approx. 640 patients.

The study will be extended by up to one year (until week 104). In the
Netherlands, the extension will be about half a year.
The Netherlands also participates in the extension of this study despite
secukinumab now registered and available in the Netherlands. The unblinding can
only happen as soon as the database lock of the 52 week data is performed,
expected mid-September 2015. Once the unblinding has occurred the physician can
decide with the patient to continue or change the treatment.

Treatment with secukinumab or ustekinumab.

Risk: Adverse effects of study medication.
Burden when study duration 80 weeks:
Study duration approx. 1.5 year. Approx. 25 visits. Fasting 1x. Duration 1-2 h
per visit.
Approx. 20 times s.c. administration of study medication (2 s.c.
injections/occasion).
Physical examination 11 times.
Blood tests approx. 11 times, 7-25 ml/occasion.
ECG 1 time.
4 Questionnaires (quality of life and work productivity) 10 times.
Questionnaire on pain, itching and scaling every visit up to week 28 and week
48, 52, 72 and end of study visit.