A randomized, double-blind, placebo-controlled, multicenter study to demonstrate the efficacy at 16 weeks of secukinumab 150 and 300 mg s.c. and to assess safety, tolerability and long-term efficacy up to 132 weeks in subjects with moderate to severe palmoplantar psoriasis (CAIN457A2312)

Plaque psoriasis (psoriasis vulgaris) is the most frequent clinical
presentation of psoriasis. Palmoplantar psoriasis is a variant affecting the
palms and soles, often associated with functional limitations and pain and
often resistant to many forms of therapy. Palmoplantar psoriasis may have a
severe impact on the quality of life.
A variety of treatments has been tried from topical treatments to UV light
therapy and classic systemic treatment. None of them has been shown to be very
effective. Treatment options have increased with the arrival of biological
treatments, but the place of these newer treatments is not clear yet and larger
prospective, controlled studies are required.
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 data on the use of secukinumab for moderate to
severe psoriasis that includes a significant involvement of palms and soles.
Phase III studies for secukinumab included assessments of psoriasis, but did
not include specific assessments of palms and soles. The purpose of this study
is to demonstrate the efficacy of 2 doses (150 and 300 mg) of secukinumab
versus placebo at Week 16. Treatment will continue up to 132 weeks to assess
long term efficacy, safety and tolerability. Patients will administer the
injections themselves.
Till week 80, this study is placebo-controlled. As of week 80 (protocol version
01) there is no placebo-arm anymore and subjects of placebo-group will receive
150 mg or 300 mg secukinumab s.c. 4-weekly.

Primary: To demonstrate the superiority of secukinumab 150 mg and/or 300 mg to
placebo in subjects with moderate to severe palmoplantar psoriasis as assessed
by the palmoplantar Investigator*s Global Assessment (ppIGA) at Week 16.
Secondary: Efficacy (ppIGA, ppPASI) up to week 132 Safety and tolerability.
Immunogenicity.

Multicenter randomized double-blind phase III parallel-group placebo-controlled
study (placebo-controlled till week 80).
Randomisation (1:1:1) to:
* Secukinumab 150 mg (s.c. injections every 4 weeks) *)
* Secukinumab 300 mg (s.c. injections every 4 weeks) *)
* Placebo.
*) after loading period of 4 week with weekly injections.
As of week 80 subjects placebo-group (group 3 above), randomisation 1:1:
* Secukinumab 150 mg (s.c. injections every 4 weeks)
* Secukinumab 300 mg (s.c. injections every 4 weeks)

Screening period of max. 4 weeks. Treatment period approx. 132 weeks. Follow-up
period 8 weeks.
Evaluation of efficacy at week 16. Patients on placebo and not qualifying as
ppIGA responders will be switched at week 16 to secukinumab (randomized
allocation of dose).
Approx. 200 patients.

Treatment with Secukinumab (150 or 300 mg) or placebo s.c 4-weekly.
Placebo till week 80, as of week 80 secukinumab 4-weekly 150 of 300 mg s.c. (no
placebo-arm anymore)

Risk: Adverse effects of study medication.
Burden: Study duration approx. 144 weeks. Approx. 24 visits. Fasting 6x.
Duration 2 h.
Approx. 39 times s.c. administration of study medication (2 injections of 1 mL
per occasion).
Physical examination during all visits.
Blood tests approx. 10 times, 5-10 ml/occasion.
ECG 7 times.
TBC skin test or blood test 1x.
Chest X ray 1x (if not performed in previous 3 months).
Optional photographs of affected areas 9 times.
4 Questionnaires (symptoms and quality of life) 4 times.