A randomized, multicenter Study to evaluate the Effect of secukinumab 300 mg s.c. administered during 52 Weeks to patients suffering from new-onset moderate to severe plaque Psoriasis as early Intervention compared to standard treatment with narrow band UVB (STEPin study)

A randomized, multicenter STudy to evaluate the Effect of secukinumab 300 mg
s.c. administered during 52 weeks to patients suffering from new-onset moderate
to severe plaque Psoriasis as early Intervention compared to standard treatment
with narrow band UVB (STEPIn study).

There is evidence that treatment of psoriasis during the first years is
conservative and frequently based on topical agents which rarely clear lesions
completely. Treatment with biologic systemic agents is often initiated only
when topical agents, phototherapy and conventional systemic treatment have
proved to be inadequate, even in patients with moderate to severe disease.
inhibition of IL-17A early after disease onset may be a novel and important
therapeutic approach interfering with the immune system before the
establishment of extensive and chronic inflammation.

The purpose of this study is to determine whether early intervention with
subcutaneous (s.c.) secukinumab 300 mg in patients with new-onset moderate to
severe psoriasis may lead to prolonged symptom-free periods by preventing
reactivation of old lesions or ultimately totally hindering the occurrence of
new lesions, i.e., changing the natural course of the disease (Main Study).

Primary objective: To demonstrate that early treatment with secukinumab 300 mg
s.c. (Arm A1) is superior to standard of care treatment with nb-UVB (Arm B1) in
patients with new-onset moderate to severe psoriasis with respect to patients
achieving * 90% improvement (reduction) in psoriasis area and severity index
(PASI 90) response at Week 52.

Key secondary objective: To evaluate the superiority of early treatment with
secukinumab (Arm A1) versus nb-UVB (Arm B1) based on the proportion of all
randomized patients who achieve at least PASI 90 at Week 104.

The design consists of the Main Study (with 3 clinical epochs: Screening Epoch,
Treatment Epoch, and Follow-up Epoch) and a Mechanistic Sub-study (with 2
epochs: Screening Epoch and Treatment Epoch).

The Main Study is multicenter, randomized, 2-treatment-arm (secukinumab and
nb-UVB), parallel-group and not blinded.

The Mechanistic Sub-study comprises 5 treatment arms (A1b, A2, B1, C1, and C2).

Secukinumab (AIN457) 300 mg
Narrow-band UVB

Risks:
Secukinumab has the potential to increase the risk of infections. In clinical
studies, infections (e.g., nasopharyngitis, upper respiratory tract infections,
oral herpes, pharyngitis, sinusitis, tinea pedis, conjunctivitis, tonsillitis,
oral candidiasis) have been observed in patients receiving secukinumab. Most of
these were mild or moderate.

The main risk derived from the treatment with nb-UVB is the occurrence of *sun
burn* leading to itching, irritation, redness of the skin, and tanning.
Calcipotriol (component of the combination product calcipotriol 50 *g/g and
betamethasone 0.5 mg/g), which is given for the first 4 weeks of each cycle of
nb-UVB, may also cause redness and itching. The risk of skin cancer is
considered minimal.

The risk to study patients will be minimized by complying with the eligibility
criteria and study procedures and close clinical monitoring.

Burden:
Psoriasis area severity index scores outcome measures, the assessment of the
severity of the psoriasis symptoms and the extent to which the patient*s body
area is affected by the disease, is mandated by the EMA for the clinical
investigation of medicinal products for the treatment of psoriasis.

Benefits:
The current hypothesis is that early intensive intervention with biological
drugs in the autoimmune process dampens the immune mechanism that leads to a
chronic inflammatory disease. In rheumatoid arthritis it has been shown that
early intervention can modify disease activity (in particular bone erosion) and
severity outcomes.
The potential benefits of early intensive intervention with secukinumab may
result in quick clearance of psoriatic plaques and prolong relapse-free periods
or complete prevention of relapses. Patients may benefit from 1 or 2 years of
treatment that has been proven to be effective for at least 1 year.