Secukinumab Therapy for the Treatment of Moderate to Severe Plaque Psoriasis With Response Monitoring Using Optical Coherence Tomography (OCT).

Secukinumab, an anti-IL-17A monoclonal antibody, is an effective treatment for moderate to
severe plaque psoriasis.While there is an abundance of clinical data in the literature
supporting the clinical efficacy of this therapy, there is limited data on early disease
clearance and other histologic findings elucidating a drug mechanism of action.
Hyper-proliferation of the epidermis and inflammation of dermis seen in psoriasis are thought
to be due to persistent T-cell activation and production of several pro-inflammatory
cytokines by dermal immune reaction. Therefore, with treatments with immunomodulatory
effects, such as Secukinumab, monitoring markers of inflammation, angiogenesis, and collagen
synthesis would be useful in establishing mechanism of action. While a skin biopsy can show
these findings at one moment in time, it does not allow for repetitive monitoring overtime.
The investigators propose the use of non-invasive imaging with Optical Coherence Tomography
(OCT) to demonstrate histologic features of plaque psoriasis not clinically evident. Upon
completion of the study, the investigators will assess when OCT improvements of psoriasis
treatment are detectable and how these findings correlate to observed clinical improvements.

Inclusion Criteria:

1. Male or female subject at least 18 years of age with a diagnosis of moderate to severe
chronic plaque psoriasis vulgaris for at least 6 months.

2. Subjects must be candidates for systemic therapy and have at least moderate to severe
psoriasis, as defined by the Psoriasis Area and Severity Index (PASI) score: body
surface area (BSA) involvement >10% , PASI >12 and/or IGA modified (mod 2011) score of
3 ("moderate") or 4 ("severe"). [2-4]

3. Patients must be naïve to prior biologic treatment

4. Subject is able to provide written informed consent and comply with the requirements
of this study protocol.

5. Subjects who are women of childbearing potential must have a negative urine pregnancy
test at screening and must be practicing an adequate, medically acceptable method of
birth control for at least 30 days before Day 0 and at least 6 months after the last
study drug administration. Acceptable methods of birth control include intrauterine
device (IUD); oral, transdermal, implanted or injected hormonal contraceptives (must
have been initiated at least 1 month before entering the study); tubal ligation;
abstinence and barrier methods with spermicide. Otherwise, if not of childbearing
potential, subjects must: have a sterile or vasectomized partner; have had a
hysterectomy, a bilateral oophorectomy or be clinically diagnosed infertile; or be in
a menopausal state for at least a year.

6. Tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT)
negative at the time of screening, or if patient has a history of positive PPD or
QuantiFERON, he/she has completed the appropriate prophylaxis.

7. Subject is judged to be in good general health as determined by the principal
investigator based upon the results of medical history, laboratory profile, and
physical examination.

Exclusion Criteria:

1. Patients with guttate, erythrodermic, exfoliative, or pustular psoriasis, other skin
conditions affecting the treatment area, severe hepatic disorders or severe renal
insufficiency

2. Have received systemic psoriasis treatments (such as psoralen and PUVA light therapy,
cyclosporine, corticosteroids, methotrexate, retinoids, mycophenolate, hydroxyurea,
azathioprine, sirolimus) or phototherapy within the previous 4 weeks; or have had
topical therapy within the previous 2 weeks.

3. Have received any biologic agent for the treatment of psoriasis, including etanercept,
infliximab or adalimumab, alefacept, ustekinumab, or any other biologic agent

4. Use of other drugs with potential effect on psoriasis, such as beta blockers,
antimalarials, angiotensin-converting enzyme inhibitors, and lithium, are allowed,
provided that treatment was not initiated and the dosage did not change during the
trial.

5. Any subject who is pregnant or refuses to practice an acceptable method of birth
control (as stated in inclusion criterion # 4)

6. History of an ongoing, chronic or recurrent infectious disease, or evidence of
tuberculosis infection as defined by a positive tuberculin purified protein derivative
(PPD) or QuantiFERON TB-Gold test (QFT) at screening. Subjects with a positive or
indeterminate PPD or QFT test may participate in the study if a full tuberculosis work
up (according to local practice/guidelines) is completed within 12 weeks prior to
randomization and establishes conclusively that the subject has no evidence of active
tuberculosis. If presence of latent tuberculosis is established, then treatment must
have been initiated at least for 4 weeks prior to randomization and the course of
prophylaxis is planned to be completed.

7. Active Crohn's disease

8. History of significant allergies or intolerances

9. Imumunocompromised patients, including Subjects with a history of TB, HIV, Hepatitis B
or Hepatitis C infections

10. Have had live vaccination within 12 weeks prior to study

11. Have evidence of active infection, such as fever, within 5 days of dosing