Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of AMG 557 in Adults With Psoriasis

Inclusion Criteria:

- Subjects must sign an Institutional Review Board (IRB)-approved informed consent form
(ICF) before any study specific procedures.

- Diagnosis of moderate to severe plaque PsO for at least 6 months prior to screening
as defined by:

- A minimum PASI score of ≥ 10 obtained at screening;

- Psoriasis involving ≥ 10% of the Body Surface Area (BSA) at screening.

- Received at least 1 previous phototherapy or systemic PsO therapy (but not within the
30 days before study drug administration), or has been a candidate to receive
phototherapy or systemic PsO therapy in the opinion of the PI.

- Stable treatment without topical or systemic steroids, topical or systemic retinoids,
vitamin D analogues (Dovenex), Psoralen Ultraviolet A (PUVA) therapy, Ultraviolet A
(UVA) therapy or Ultraviolet B (UVB) therapy, methotrexate, or cyclosporine for at
least 60 days prior to IP administration. Stable treatment of PsO involving scalp,
axillae, or groin with topical corticosteroids of moderate strength will be allowed.

- Agrees to wear clothing that protects from sun exposure for the duration of the
study.

- Agrees to use sunscreen (SPF of at least 30) on sun-exposed skin for the duration of
the study.

- Male or female subjects between 18 and 55 years of age, inclusive at the time of
screening.

- Body mass index (BMI) between 18 and 35 kg/m2, inclusive, at screening, unless
considered by the PI and the Amgen Medical Monitor to be at an appropriate value in
the context of other measured safety parameters.

- Able and willing to complete entire study (including skin biopsies) according to
study schedule.

- Additional criteria per protocol.

Exclusion Criteria:

- Diagnosis of guttate, pustular, or other non plaque forms of PsO.

- Evidence of skin conditions other than PsO (eg, eczema) during the screening period
that would interfere with evaluations of the effect of IP on PsO.

- Previous receipt of any approved or investigational biologic agent for PsO or other
medical conditions.

- Received PUVA therapy, UVA therapy or UVB therapy ≤ 30 days prior to IP
administration.

- Treatment with any other systemic PsO therapy or oral or parenteral corticosteroids ≤
30 days prior to IP administration.

- Use of high potency topical steroids, topical vitamin A or D analog preparations, or
anthralin ≤ 30 days prior to IP administration (Note: stable doses > 30 days of low
or moderate strength topical steroids are permitted only on the scalp, axillae, and
groin according to the package insert).

- Received topical cyclosporin or calcineurin inhibitors such as pimecrolimus (Elidel)
and tacrolimus (Protopic) ≤ 30 days prior to IP administration.

- Received IV or oral calcineurin inhibitors such as tacrolimus (Prograf) ≤ 30 days
prior to IP administration.

- Significant concurrent medical conditions at the time of screening or prior to
randomization, including:

- Uncontrolled hypertension (defined as screening systolic blood pressure
measurement of greater than 140 mm Hg or a screening diastolic blood pressure of
greater than 90 mm Hg) confirmed by 2 separate measurements during the screening
visit;

- Unstable angina pectoris;

- Congestive heart failure;

- Steroid or oxygen dependent chronic obstructive pulmonary disease;

- Diagnosis of multiple sclerosis or any other demyelinating disease;

- Open cutaneous ulcers;

- Uncontrolled diabetes (HbA1c > 7%).

- History of myocardial infarction.

- Subjects with two or more cardiovascular risk factors (defined as BMI > 30, BP
systolic > 140 mm Hg, diagnosis of diabetes, history of cardiovascular event).

- Evidence of significant renal insufficiency during the screening period, defined by a
glomerular filtration rate < 50 mL/min using the Cockcroft and Gault equation:

72 x Serum Creatinine (in mg/dL) / (140 - Age) x Body Weight (in kg) x [0.85 if
female]

- Evidence of any bacterial, viral, parasitic, or systemic fungal infections during the
30 days prior to study drug administration (eg, common cold, viral syndrome, flu like
symptoms).

- Evidence of a recent (within 6 months of randomization) infection requiring in
patient hospitalization or intravenous antibiotics.

- Positive test for HIV antibodies, hepatitis B surface antigen, or hepatitis C
antibodies.

- Underlying condition that predisposes the subject to infections (eg, history of
splenectomy; history of immunodeficiency).

- Evidence of past or active tuberculosis on chest x-ray performed during screening (or
documented evidence on a chest x-ray performed within 6 months prior to planned
dosing); known tuberculosis antecedents; known exposure (without adequate treatment)
to a person with active tuberculosis; or positive protein purified derivative (PPD)
Mantoux skin or serum quantiferon test at screening (without documented history of
treatment). A positive result is defined as either induration greater than or equal
to 5 mm 48-72 hours after administration (Mantoux) or a positive serum quantiferon
test result.

- History of malignancy.

- Evidence of liver disease (eg, serum ALT and AST > 1.5 x the upper limit of normal)
during screening period.

- Donated blood (including blood products) or experienced loss of blood ≥ 500 mL within
2 months of screening.

- Additional criteria per protocol.