Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 827

Study Overview
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Brief Summary
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This Phase 1 study will evaluate safety, tolerability, PK and PD of AMG 827 when administered as a single SC or IV dose.

Detailed Description
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This Phase 1 study will evaluate safety, tolerability, PK and PD of AMG 827 when administered as a single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).

Official Title
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A Randomized, Double-blind, Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 827 in Healthy Subjects and Subjects With Moderate to Severe Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: 700 mg IV
* Drug: 350 mg SC
* Drug: Placebo
* Drug: 140 mg SC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A: Able to provide written informed consent Healthy male or female between 18 to 45 years of age, inclusive at the time of screening Additional inclusion criteria apply Part B: 18 - 55 years old inclusive at Screening Active but clinically stable, plaque psoriasis Psoriasis involving ≥ 10% of the body surface area A minimum PASI score of ≥ 10 obtained during the screening period Additional inclusion criteria apply Exclusion Criteria: Part A: History or evidence of a clinically significant disorder (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric), condition or disease that, in the opinion of the Investigator and Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion Underlying condition that predisposes the subject to infections (eg, uncontrolled diabetes - HbA1c > 7%, history of splenectomy) Additional exclusion criteria apply Part B: Active guttate, erythrodermic, or pustular psoriasis at the time of the screening visit Evidence of skin conditions other than psoriasis (eg, eczema) at the time of the screening visit or between the screening visit and study drug initiation that would interfere with evaluations of the effect of investigational product on psoriasis Any condition that, in the judgment of the investigator, might cause this study to be detrimental to the subject Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo treatment | Drug: Placebo<br>* single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).<br>|
| Experimental: 140 mg SC<br>140 mg SC PsO | Drug: 140 mg SC<br>* single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).<br>|
| Active Comparator: 350 mg SC<br>350 mg SC PsO | Drug: 350 mg SC<br>* single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).<br>|
| Experimental: 700 mg IV<br>700 mg IV PsO | Drug: 700 mg IV<br>* single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43 | Summary of percent change in PASI (Psoriasis Area Severity Index) Scores over time by treatment groups between baseline and day 43, PASI score ranging from (0) no disease to (72) maximal disease. | Through day 43 | 
| Part B: All Treatment Adverse Events Reported for Safety Evaluation | This primary outcome assesses number of participants iwth any reported adverse events emerging during treatment period. | 85 days | 
| Part A: All Treatment Adverse Events Reported for Safety Evaluation | This primary outcome assesses the number of participants with any reported adverse events emerging during treatment period. | Cohort 1-4 43 days, Cohort 5-8 64 days |