Treatment for Patients With Osteoarthritis (OA)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical benefit (change in Western Ontario and McMaster University Osteoarthritis Index [WOMAC] pain score) of AMG 108 (300 mg subcutaneously [SC] every 4 weeks) in subjects with OA.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Systemic AMG 108 in Subjects With Osteoarthritis (OA)

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: Systemic AMG 108
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with knee OA as determined by American College of Rheumatology (ACR) criteria Pain defined by a level of greater than or equal to 30 mm on a 100 mm Visual Analogue Scale (VAS) If currently taking any over the counter nutritional supplements, must be on stable doses for greater than 2 months prior to screening If utilizing physical therapy, biomechanical devices or orthotic support, must have been using treatment or device for greater than or equal to 2 months prior to screening If currently or previously taking any non-prescribed supplement (e.g., glucosamine or chondroitin sulphate, shark cartilage, diacerein, soya extract, etc.) must be on stable doses for at least 2 months prior to screening If currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), must be on stable doses for at least 2 months prior to screening Able to discontinue NSAIDs at least 5 half-lives (approximately 3 days) prior to Day 1 Radiographic evidence of tibio-femoral compartment knee OA within 12 months of screening Signed written informed consent Exclusion Criteria: Malignancy within the previous 5 years, except for basal cell or in situ cancer Significant hematologic disease - Active infection or history of recurrent or chronic infections Known diagnosis of HIV, hepatitis B, or hepatitis C infection Uncontrolled diabetes or cardiovascular disease and hypertension Inflammatory arthropathy including secondary OA Isolated OA of the patellofemoral joint (bi or tri-compartmental involvement are not exclusions) End-stage (bone-on-bone) OA (Kellgren Lawrence score of 4) OA of the hip ipsilateral to the index knee - Total white cell count less than 2.0 x 10^9/L and/or platelet count less than 100 x 10^9/L observed within 1 month preceding screening Prior intra-articular (IA) injection of anakinra or experimental interleukin-1 (IL-1) inhibitor therapy - Concurrent treatment with SC anakinra Concurrent or recent (less than or equal to 1 month) use of experimental therapy Prior IA corticosteroid injection within 1 month of study Prior viscosupplement therapy within 3 months of study Contraindication(s) to IA injections Subjects who are pregnant or breast-feeding, or plan to become pregnant during the study Subject is not using adequate contraception Known allergy to E coli-derived products Unable to understand informed consent Concerns regarding subject's compliance with the protocol procedures Subject will not be available for follow-up assessment Active substance abuse

Ages Eligible for Study
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Minimum Age: 30 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Minor sub-study AMG 108<br>N = 15 | Drug: Systemic AMG 108<br>* 300 mg SC AMG 108 Q4W for 3 doses<br>|
| Placebo Comparator: Minor sub-study placebo<br>N = 15 | Other: Placebo<br>* SC placebo injection Q4W for 3 doses<br>|
| Active Comparator: Main sub-study AMG 108<br>N = 73 | Drug: Systemic AMG 108<br>* 300 mg SC AMG 108 Q4W for 3 doses<br>|
| Placebo Comparator: Main sub-study placebo<br>N = 73 | Other: Placebo<br>* SC placebo injection Q4W for 3 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in WOMAC pain score |  | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in WOMAC pain score |  | Week 12 | 
| Change in WOMAC composite score and function and stiffness index scores |  | Weeks 6 and 12 | 
| Achieving 50% or more improvement from Day 1 in the WOMAC |  | Weeks 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intra-articular, Osteoarthritis, OA, anakinra, Amgen