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

Phase 2

Terminated

• Conditions: Osteoarthritis, Knee; Pain
• Interventions: Drug: ONO-4474; Drug: Placebo matching ONO-4474

• Registration Number: NCT02997696
• Lead Sponsor: Ono Pharmaceutical Co. Ltd

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-12-02
• Study First Submitted QC: 2016-12-15
• Study First Posted: 2016-12-20
• Study Start: 2017-01
• Primary Completion: 2018-01-09
• Study Completion: 2018-01-09
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-23
• Last Update Posted: 2018-02-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 70

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental arm 1	ONO-4474	ONO-4474 low dose every day for 4 weeks
Experimental arm 2	ONO-4474	ONO-4474 high dose every day for 4 weeks
Placebo arm	Placebo matching ONO-4474	Placebo matching ONO-4474 every day for 4 weeks

Primary Outcome Measures

Name	Time	Method
Change from baseline in mean daily average index knee pain while walking	Week 4

Secondary Outcome Measures

Name	Time	Method
Safety of ONO-4474 as assessed by neurological examination	From baseline to study completion, an average of 6 weeks
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 Patient Global Assessment	Week 1, Week 2, Week 4 and Weeks 1-4
Pharmacokinetics of ONO-4474 in plasma: Ctrough of ONO-4474	Week 1, Week 2 and Week 4
Change from baseline in mean daily average index knee pain while walking	Week 1, Week 2, Week 3 and Weeks 1-4
Improvement score in Clinical Global Impression	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
Use of rescue medication as total number of tablets taken	Week 1, Week 2, Week 3, Week 4
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
Change from baseline in: EuroQoL EQ-5D-5L	Week 4
Time to first rescue medication use	Week 4

Trial Locations

Locations (19)

Investigational Site; 🇬🇧 Romford, United Kingdom

Investigational Site 4808; 🇵🇱 Bialystok, Poland

Investigational Site 4818; 🇵🇱 Bialystok, Poland

Investigational Site 4815; 🇵🇱 Warszawa, Poland

Investigational Site 4801; 🇵🇱 Zamosc, Poland

Investigational Site 3406; 🇪🇸 Barcelona, Spain

Investigational Site 3402; 🇪🇸 Madrid, Spain

Investigational Site 3407; 🇪🇸 Barcelona, Spain

Investigational Site 3410; 🇪🇸 Madrid, Spain

Investigator Site; 🇪🇸 Santiago de Compostela, Spain

Investigational site; 🇪🇸 Villajoyosa, Spain

Investigational Site 4401; 🇬🇧 Leeds, United Kingdom

Investigational Site 4410; 🇬🇧 Leeds, United Kingdom

Investigational Site 4504; 🇩🇰 Odense, Denmark

Investigational Site 4819; 🇵🇱 Bialystok, Poland

Investigational Site 4812; 🇵🇱 Krakow, Poland

Investigational Site 4811; 🇵🇱 Warszawa, Poland

Investigational Site 4810; 🇵🇱 Krakow, Poland

Investigational Site 4816; 🇵🇱 Zamosc, Poland