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

• Status: Terminated
• Trial end date: 2013-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to study the safety, tolerability and immunogenicity of AMG 557 following multiple subcutaneous dose administration in adults with moderate to severe psoriasis.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amgen

Criteria

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.