Osteoarthritis, Knee, Pain
Conditions
Brief summary
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.
Interventions
DRUGONO-4474
DRUGPlacebo matching ONO-4474
Sponsors
Ono Pharmaceutical Co. Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
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, 1. 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), 2. RPOA, osteonecrosis, osteoporotic fracture or any other painful joint disease other than OA, 3. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in mean daily average index knee pain while walking | Week 4 |
Secondary
| Measure | 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 |
Other
| Measure | Time frame |
|---|---|
| Percentage of patients who report a ≥30%, ≥50% or ≥70% decrease versus baseline in mean daily average index knee pain while walking | Weeks 1, 2, 3 and 4, and Weeks 1-4 |
| Percentage of patients who report a ≥30%, ≥50% or ≥70% decrease versus baseline in WOMAC pain score | Weeks 1, 2 and 4, and Weeks 1-4 |
| Percentage of patients who report a ≥30%, ≥50% or ≥70% decrease versus baseline in WOMAC physical function score | Weeks 1, 2 and 4, and Weeks 1-4 |
| Change from baseline to study completion in mean daily average index knee pain while walking | From baseline to study completion, an average of 6 weeks |
| Change from baseline to study completion in WOMAC pain score | From baseline to study completion, an average of 6 weeks |
| Change from baseline to study completion in WOMAC physical function score | From baseline to study completion, an average of 6 weeks |
| Change from baseline to study completion in PGA | From baseline to study completion, an average of 6 weeks |
| Change of daily average index knee pain while walking versus daily physical activity | From baseline to study completion, an average of 6 weeks |
| Change of average index knee pain versus daily physical activity | From baseline to study completion, an average of 6 weeks |
| Ctrough versus change from baseline to Weeks 1, 2 and 4 in WOMAC pain score | Week 1, Week 2 and Week 4 |
| Ctrough versus change from baseline to Weeks 1, 2 and 4 in WOMAC physical function score | Week 1, Week 2 and Week 4 |
| Ctrough versus change from baseline to Weeks 1, 2 and 4 in PGA | Week 1, Week 2 and Week 4 |
| Percentage of patients who meet Osteoarthritis Research Society International - Outcome Measures in Rheumatology (OMERACT-OARSI) responder criteria | Week 1, Week 2 and Week 4 |
Countries
Denmark, Hungary, Poland, Spain, United Kingdom
Outcome results
None listed