A Study to Evaluate ONO-4474 in Patients With Pain Due to Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The purpose of this phase 2, randomised, double-blind, placebo controlled, parallel group, multicentre study is to investigate the efficacy, safety, tolerability and pharmacokinetics of a compound ONO-4474 in patients with moderate to severe pain due to osteoarthritis of the knee following 4 weeks of oral administration of ONO-4474.

Official Title
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A Randomised, Double-blind, Placebo Controlled, Parallel Group, Multi-centre, Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of ONO-4474 in Patients With Pain Due to Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee, Pain

Intervention / Treatment
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* Drug: ONO-4474
* Drug: Placebo matching ONO-4474


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic OA of the knee for ≥3 months diagnosed prior to screening as per American College of Rheumatology clinical criteria. Radiographic evidence of tibiofemoral OA of index knee (Kellgren-Lawrence grade 2-3), as confirmed at screening. Moderate to severe index knee pain due to OA requiring use of analgesic medication. Willing to discontinue use of all analgesic medication (aside from rescue medication) during the study. Exclusion Criteria: Presence of, or history of, any inflammatory arthritis (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthropathy, septic arthritis, previous diagnosis of pseudogout in target joint with proven crystals on joint aspiration or elevated C-Reactive Protein (CRP) at time of knee arthritis flare), RPOA, osteonecrosis, osteoporotic fracture or any other painful joint disease other than OA, Secondary causes of OA; other rheumatologic or musculoskeletal conditions (e.g., rheumatoid arthritis, fibromyalgia, septic arthritis, congenital abnormality). Orthopaedic surgery of a lower extremity or any major surgery within the previous 6 months prior to Visit 1 or has plans for surgical intervention during the study. Symptomatic hip OA. A history of partial or complete joint replacement surgery in the index knee at any time or anticipating knee surgery during the study period. Significant knee injury or any knee surgery (including arthroscopy) in the index knee within 6 months prior to screening. Uncontrolled diabetes.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Experimental arm 1<br>ONO-4474 low dose every day for 4 weeks | Drug: ONO-4474<br> <br> |
| Experimental: Experimental arm 2<br>ONO-4474 high dose every day for 4 weeks | Drug: ONO-4474<br> <br> |
| Placebo Comparator: Placebo arm<br>Placebo matching ONO-4474 every day for 4 weeks | Drug: Placebo matching ONO-4474<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean daily average index knee pain while walking |  | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile assessed by adverse events, vital signs, laboratory tests, 12-lead electrocardiograms (ECG), physical examination |  | From baseline to study completion, an average of 6 weeks | 
| Safety of ONO-4474 as assessed by C-SSRS (evaluation of suicidal ideation and behavior) |  | From baseline to study completion, an average of 6 weeks | 
| Safety of ONO-4474 as assessed by neurological examination |  | From baseline to study completion, an average of 6 weeks | 
| Change from baseline in mean daily average index knee pain while walking |  | Week 1, Week 2, Week 3 and Weeks 1-4 | 
| Change from baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, stiffness and physical function scores |  | Week 1, Week 2, Week 4 and Weeks 1-4 | 
| Change from baseline in overall WOMAC score |  | Week 1, Week 2, Week 4 and Weeks 1-4 | 
| Change from baseline in mean daily average index knee pain |  | Week 1, Week 2, Week 3, Week 4 and Weeks 1-4 | 
| Change from baseline in Patient Global Assessment |  | Week 1, Week 2, Week 4 and Weeks 1-4 | 
| Improvement score in Clinical Global Impression |  | Week 1, Week 2, Week 4 and Weeks 1-4 | 
| Change from baseline in: EuroQoL EQ-5D-5L |  | Week 4 | 
| Use of rescue medication as total number of tablets taken |  | Week 1, Week 2, Week 3, Week 4 | 
| Time to first rescue medication use |  | Week 4 | 
| Pharmacokinetics of ONO-4474 in plasma: Ctrough of ONO-4474 |  | Week 1, Week 2 and Week 4 |