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

NCT02997696 | Terminated Phase 2

• 2 other identifiers: ONO-4474-022016-002675-97
• Study Type: interventional
• Target: 70
• Locations: 5 countries
• Sites: 47

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.

Conditions

Osteoarthritis, Knee; Pain

Outcome Measures

Primary Outcomes (1)

• Change from baseline in mean daily average index knee pain while walking

  Week 4

Secondary Outcomes (13)

• 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

Other Outcomes (13)

• 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

Study Arms (3)

Experimental arm 1

EXPERIMENTAL

ONO-4474 low dose every day for 4 weeks

Drug: ONO-4474

Experimental arm 2

EXPERIMENTAL

ONO-4474 high dose every day for 4 weeks

Drug: ONO-4474

Placebo arm

PLACEBO COMPARATOR

Placebo matching ONO-4474 every day for 4 weeks

Drug: Placebo matching ONO-4474

Interventions

ONO-4474 DRUG

Experimental arm 1; Experimental arm 2

Placebo matching ONO-4474 DRUG

Placebo arm

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (47)

Investigational Site

Aalborg, Denmark

Location

Investigational Site

Frederiksberg, Denmark

Location

Investigational Site 4504

Odense, Denmark

Location

Investigational Site

Balatonfüred, Hungary

Location

Investigational Site

Budapest, Hungary

Location

Investigational Site

Eger, Hungary

Location

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Kistarcsa, Hungary

Location

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Mezőkövesd, Hungary

Location

Investigational Site

Szolnok, Hungary

Location

Investigational Site 4808

Bialystok, Poland

Location

Investigational Site 4818

Bialystok, Poland

Location

Investigational Site 4819

Bialystok, Poland

Location

Investigational Site

Elblag, Poland

Location

Investigational Site

Gdynia, Poland

Location

Investigational Site

Katowice, Poland

Location

Investigational Site

Kielce, Poland

Location

Investigational Site 4810

Krakow, Poland

Location

Investigational Site 4812

Krakow, Poland

Location

Investigational Site

Lublin, Poland

Location

Investigational Site

Nadarzyn, Poland

Location

Investigational Site

Poznan, Poland

Location

Investigational Site

Siedlce, Poland

Location

Investigational Site

Staszów, Poland

Location

Investigational Site 4811

Warsaw, Poland

Location

Investigational Site 4815

Warsaw, Poland

Location

Investigational Site

Wroclaw, Poland

Location

Investigational Site 4801

Zamość, Poland

Location

Investigational Site 4816

Zamość, Poland

Location

Investigational Site

A Coruña, Spain

Location

Investigational Site 3406

Barcelona, Spain

Location

Investigational Site 3407

Barcelona, Spain

Location

Investigational Site 3402

Madrid, Spain

Location

Investigational Site 3410

Madrid, Spain

Location

Investigational Site

Móstoles, Spain

Location

Investigational Site

Sabadell, Spain

Location

Investigator Site

Santiago de Compostela, Spain

Location

Investigational Site

Seville, Spain

Location

Investigational site

Villajoyosa, Spain

Location

Investigational Site

Barnsley, United Kingdom

Location

Investigational Site

Blackpool, United Kingdom

Location

Investigational Site 4401

Leeds, United Kingdom

Location

Investigational Site 4410

Leeds, United Kingdom

Location

Investigational Site

Liverpool, United Kingdom

Location

Investigational Site

Manchester, United Kingdom

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Middlesex, United Kingdom

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North Shields, United Kingdom

Location

Investigational Site

Romford, United Kingdom

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Philip Conaghan, MBBS PhD

  Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 20, 2016
• Study Start: January 1, 2017
• Primary Completion: January 9, 2018
• Study Completion: January 9, 2018
• Last Updated: February 26, 2018

Record last verified: 2018-02

Locations

GB (9); DK (3); HU (6); PL (19); ES (10)