A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 282 in Healthy Subjects and Subjects With Chronic Rhinosinusitis With Nasal Polyps

Study Overview
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Brief Summary
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A randomized, double-blind, ascending multiple dose study in healthy volunteers and subjects with chronic rhinosinusitis with nasal polyps

Official Title
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A Randomized, Double-blind, Placebo-controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 282 in Healthy Subjects and Subjects With Chronic Rhinosinusitis With Nasal Polyps

Conditions
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Chronic Rhinosinusitis With Nasal Polyps

Intervention / Treatment
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* Drug: AMG 282
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Healthy Volunteers: Inclusion Criteria: Healthy males and females witha BMI between 18.0 and 32.0 kg/m2, inclusive Exclusion Criteria: subject with evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with study evaluation, procedures, or completion. Subjects with chronic rhinosinusitis with nasal polyps (CRSwNP): Inclusion Criteria: diagnosis of CRSwNP (inflammation of the nose and paranasal sinuses characterized in adults by 2 or more symptoms, 1 of which should be either nasal blockage or nasal discharge and/or facial pain and/or reduced smell for greater than 12 weeks) bilateral nasal polyps of grade 3 or 4 Exclusion Criteria: Forced Expiratory Volume (FEV1) </= 70% Asthma exacerbation requiring systemic corticosteroid treatment or hospitalization for > 24h for treatment of asthma, within 3 months prior to screening or are on a dose of greater than 1000 μg fluticasone.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 282<br>AMG 282 administered as subcutaneous and intravenous doses. | Drug: AMG 282<br>* AMG 282 is for the treatment of subjects with chronic rhinosinusitis with nasal polyps<br>|
| Placebo Comparator: Placebo<br>No active drug | Drug: Placebo<br>* Contains no active drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Subject incidence of treatment-emergent adverse events, vital signs, physical examinations, laboratory safety tests, and 12-lead electrocardiograms (ECGs) | 169 days | 
| Immunogenicity | Subject incidence of anti-AMG 282 antibodies | 169 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of AMG 282 | Serum concentrations and derived PK parameters (eg, time to maximum concentration [tmax], area under the concentration-time curve over the dosing interval τ [AUCτ] after the first and last dose, and maximum observed concentration [Cmax]). | 169 days |