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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pain; Osteoarthritis, Knee
• Intervention / Treatment: Drug: ONO-4474; Drug: Placebo matching ONO-4474

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Investigational Site
  • Frederiksberg, Denmark
    • Investigational Site
  • Odense, Denmark
    • Investigational Site 4504
• Hungary
  • Balatonfured, Hungary
    • Investigational Site
  • Budapest, Hungary
    • Investigational Site
  • Eger, Hungary
    • Investigational Site
  • Kistarcsa, Hungary
    • Investigational Site
  • Mezokovesd, Hungary
    • Investigational Site
  • Szolnok, Hungary
    • Investigational Site
• Poland
  • Bialystok, Poland
    • Investigational Site 4808
  • Bialystok, Poland
    • Investigational Site 4818
  • Bialystok, Poland
    • Investigational Site 4819
  • Elblag, Poland
    • Investigational Site
  • Gdynia, Poland
    • Investigational Site
  • Katowice, Poland
    • Investigational Site
  • Kielce, Poland
    • Investigational Site
  • Krakow, Poland
    • Investigational Site 4810
  • Krakow, Poland
    • Investigational Site 4812
  • Lublin, Poland
    • Investigational Site
  • Nadarzyn, Poland
    • Investigational Site
  • Poznan, Poland
    • Investigational Site
  • Siedlce, Poland
    • Investigational Site
  • Staszow, Poland
    • Investigational Site
  • Warszawa, Poland
    • Investigational Site 4811
  • Warszawa, Poland
    • Investigational Site 4815
  • Wroclaw, Poland
    • Investigational Site
  • Zamosc, Poland
    • Investigational site 4801
  • Zamosc, Poland
    • Investigational Site 4816
• Spain
  • A Coruna, Spain
    • Investigational Site
  • Barcelona, Spain
    • Investigational Site 3406
  • Barcelona, Spain
    • Investigational Site 3407
  • Madrid, Spain
    • Investigational Site 3402
  • Madrid, Spain
    • Investigational Site 3410
  • Mostoles, Spain
    • Investigational Site
  • Sabadell, Spain
    • Investigational Site
  • Santiago de Compostela, Spain
    • Investigator site
  • Sevilla, Spain
    • Investigational Site
  • Villajoyosa, Spain
    • Investigational Site
• United Kingdom
  • Barnsley, United Kingdom
    • Investigational Site
  • Blackpool, United Kingdom
    • Investigational Site
  • Leeds, United Kingdom
    • Investigational Site 4401
  • Leeds, United Kingdom
    • Investigational Site 4410
  • Liverpool, United Kingdom
    • Investigational Site
  • Manchester, United Kingdom
    • Investigational Site
  • Middlesex, United Kingdom
    • Investigational Site
  • North Shields, United Kingdom
    • Investigational Site
  • Romford, United Kingdom
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm 1; ONO-4474 low dose every day for 4 weeks	Drug: ONO-4474
Experimental: Experimental arm 2; ONO-4474 high dose every day for 4 weeks	Drug: ONO-4474
Placebo Comparator: Placebo arm; Placebo matching ONO-4474 every day for 4 weeks	Drug: Placebo matching ONO-4474

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
Percentage of patients who meet Osteoarthritis Research Society International - Outcome Measures in Rheumatology (OMERACT-OARSI) responder criteria	Week 1, Week 2 and Week 4
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

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Investigators: Principal Investigator: Philip Conaghan, MBBS PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): January 9, 2018
• Study Completion (Actual): January 9, 2018

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 15, 2016
• First Posted (Estimate): December 20, 2016

Study Record Updates

• Last Update Posted (Actual): February 26, 2018
• Last Update Submitted That Met QC Criteria: February 23, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: ONO-4474-02; 2016-002675-97 (EudraCT Number)