A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 403 in Subjects With Osteoarthritis Knee Pain

Study Overview
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Brief Summary
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This is a sequential, randomized, double-blind, placebo controlled, multiple dose, dose escalation study in subjects with OA knee pain (n=32; 8/cohort). In each cohort, subjects will be randomized 3:1 to receive SC AMG 403 or placebo once every 4 weeks for a total of 4 doses (Q28D x 4).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 403 in Younger and Older Subjects With Osteoarthritis Knee Pain

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: AMG 403
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with knee OA as determined by ACR criteria: Knee pain and radiographic osteophytes and at least 1 of the following 2 items: Morning stiffness 30 minutes, Crepitus on motion, a VAS pain score of ≥ 30 mm for index knee at screening, Exclusion Criteria: Weight of > 125 kg, Inflammatory arthropathy including secondary OA (eg, degenerative arthritis in patients with rheumatoid arthritis) as confirmed by a rheumatologist or investigator, Diagnosis of a condition other than knee OA that, in the investigator's opinion, may cause or affect pain or pain assessment in the index knee; these conditions may include but are not limited to radiculopathy or neuropathy, vasculopathy, fibromyalgia or active depression, Subjects taking neuromodulatory agents (antiepileptics or antidepressants) used as analgesic therapy for neuropathic pain

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 403<br>AMG 403 administered as subcutaneous doses | Drug: AMG 403<br>* AMG 403 for the treatment of subjects with osteoarthritis<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 as measured by subject incident of treatment-emergent adverse events, clinically significant changes in vital signs, physical examinations endpoints, clinical laboratory safety tests, and ECGs | Subject incident of treatment-emergent adverse events, clinically significant changes in vital signs, physical examinations endpoints, clinical laboratory safety tests, and ECGs | from 197 days to 211 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics profile of AMG 403 including Tmax, AUClast and Cmax | serum concentrations and derived PK parameters of AMG 403 | from 197 days to 211 days |