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

Pain Clinical Trial

— MOTION  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02997696
• Other study ID #: ONO-4474-02
• Secondary ID: 2016-002675-97
• Status: Terminated
• Phase: Phase 2
• First received: December 2, 2016
• Last updated: February 23, 2018
• Start date: January 2017
• Est. completion date: January 9, 2018

Study information

• Verified date: February 2018
• Source: Ono Pharmaceutical Co. Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: January 9, 2018
• Est. primary completion date: January 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee
• Pain

Intervention

Drug:
• ONO-4474

• Placebo matching ONO-4474

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

Denmark,  Hungary,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of patients who meet Osteoarthritis Research Society International - Outcome Measures in Rheumatology (OMERACT-OARSI) responder criteria		Week 1, Week 2 and Week 4
Other	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
Other	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
Other	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
Other	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
Other	Change from baseline to study completion in WOMAC pain score		From baseline to study completion, an average of 6 weeks
Other	Change from baseline to study completion in WOMAC physical function score		From baseline to study completion, an average of 6 weeks
Other	Change from baseline to study completion in PGA		From baseline to study completion, an average of 6 weeks
Other	Change of daily average index knee pain while walking versus daily physical activity		From baseline to study completion, an average of 6 weeks
Other	Change of average index knee pain versus daily physical activity		From baseline to study completion, an average of 6 weeks
Other	Ctrough versus change from baseline to Weeks 1, 2 and 4 in WOMAC pain score		Week 1, Week 2 and Week 4
Other	Ctrough versus change from baseline to Weeks 1, 2 and 4 in WOMAC physical function score		Week 1, Week 2 and Week 4
Other	Ctrough versus change from baseline to Weeks 1, 2 and 4 in PGA		Week 1, Week 2 and Week 4
Primary	Change from baseline in mean daily average index knee pain while walking		Week 4
Secondary	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
Secondary	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
Secondary	Safety of ONO-4474 as assessed by neurological examination		From baseline to study completion, an average of 6 weeks
Secondary	Change from baseline in mean daily average index knee pain while walking		Week 1, Week 2, Week 3 and Weeks 1-4
Secondary	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
Secondary	Change from baseline in overall WOMAC score		Week 1, Week 2, Week 4 and Weeks 1-4
Secondary	Change from baseline in mean daily average index knee pain		Week 1, Week 2, Week 3, Week 4 and Weeks 1-4
Secondary	Change from baseline in Patient Global Assessment		Week 1, Week 2, Week 4 and Weeks 1-4
Secondary	Improvement score in Clinical Global Impression		Week 1, Week 2, Week 4 and Weeks 1-4
Secondary	Change from baseline in: EuroQoL EQ-5D-5L		Week 4
Secondary	Use of rescue medication as total number of tablets taken		Week 1, Week 2, Week 3, Week 4
Secondary	Time to first rescue medication use		Week 4
Secondary	Pharmacokinetics of ONO-4474 in plasma: Ctrough of ONO-4474		Week 1, Week 2 and Week 4