Clinical trial NCT02997696: A Study to Evaluate ONO-4474 in Patients With Pain Due to Osteoarthritis of the Knee
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Pain
Lead sponsor: Ono Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
First posted: 2016-12-20
Enrollment: 70
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in mean daily average index knee pain while walking
timeFrame: Week 4
Secondary outcomes:
measure: Safety profile assessed by adverse events, vital signs, laboratory tests, 12-lead electrocardiograms (ECG), physical examination
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Safety of ONO-4474 as assessed by C-SSRS (evaluation of suicidal ideation and behavior)
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Safety of ONO-4474 as assessed by neurological examination
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Change from baseline in mean daily average index knee pain while walking
timeFrame: Week 1, Week 2, Week 3 and Weeks 1-4
measure: Change from baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, stiffness and physical function scores
timeFrame: Week 1, Week 2, Week 4 and Weeks 1-4
measure: Change from baseline in overall WOMAC score
timeFrame: Week 1, Week 2, Week 4 and Weeks 1-4
measure: Change from baseline in mean daily average index knee pain
timeFrame: Week 1, Week 2, Week 3, Week 4 and Weeks 1-4
measure: Change from baseline in Patient Global Assessment
timeFrame: Week 1, Week 2, Week 4 and Weeks 1-4
measure: Improvement score in Clinical Global Impression
timeFrame: Week 1, Week 2, Week 4 and Weeks 1-4
measure: Change from baseline in: EuroQoL EQ-5D-5L
timeFrame: Week 4
measure: Use of rescue medication as total number of tablets taken
timeFrame: Week 1, Week 2, Week 3, Week 4
measure: Time to first rescue medication use
timeFrame: Week 4
measure: Pharmacokinetics of ONO-4474 in plasma: Ctrough of ONO-4474
timeFrame: Week 1, Week 2 and Week 4
Other outcomes:
measure: Percentage of patients who meet Osteoarthritis Research Society International - Outcome Measures in Rheumatology (OMERACT-OARSI) responder criteria
timeFrame: Week 1, Week 2 and Week 4
measure: Percentage of patients who report a ≥30%, ≥50% or ≥70% decrease versus baseline in mean daily average index knee pain while walking
timeFrame: Weeks 1, 2, 3 and 4, and Weeks 1-4
measure: Percentage of patients who report a ≥30%, ≥50% or ≥70% decrease versus baseline in WOMAC pain score
timeFrame: Weeks 1, 2 and 4, and Weeks 1-4
measure: Percentage of patients who report a ≥30%, ≥50% or ≥70% decrease versus baseline in WOMAC physical function score
timeFrame: Weeks 1, 2 and 4, and Weeks 1-4
measure: Change from baseline to study completion in mean daily average index knee pain while walking
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Change from baseline to study completion in WOMAC pain score
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Change from baseline to study completion in WOMAC physical function score
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Change from baseline to study completion in PGA
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Change of daily average index knee pain while walking versus daily physical activity
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Change of average index knee pain versus daily physical activity
timeFrame: From baseline to study completion, an average of 6 weeks
measure: Ctrough versus change from baseline to Weeks 1, 2 and 4 in WOMAC pain score
timeFrame: Week 1, Week 2 and Week 4
measure: Ctrough versus change from baseline to Weeks 1, 2 and 4 in WOMAC physical function score
timeFrame: Week 1, Week 2 and Week 4
measure: Ctrough versus change from baseline to Weeks 1, 2 and 4 in PGA
timeFrame: Week 1, Week 2 and Week 4
Locations:
city: Aalborg
country: Denmark
facility: Investigational Site
city: Frederiksberg
country: Denmark
facility: Investigational Site
city: Odense
country: Denmark
facility: Investigational Site 4504
city: Balatonfured
country: Hungary
facility: Investigational Site
city: Budapest
country: Hungary
facility: Investigational Site
city: Eger
country: Hungary
facility: Investigational Site
city: Kistarcsa
country: Hungary
facility: Investigational Site
city: Mezokovesd
country: Hungary
facility: Investigational Site
city: Szolnok
country: Hungary
facility: Investigational Site
city: Bialystok
country: Poland
facility: Investigational Site 4808
city: Bialystok
country: Poland
facility: Investigational Site 4818
city: Bialystok
country: Poland
facility: Investigational Site 4819
city: Elblag
country: Poland
facility: Investigational Site
city: Gdynia
country: Poland
facility: Investigational Site
city: Katowice
country: Poland
facility: Investigational Site
city: Kielce
country: Poland
facility: Investigational Site
city: Krakow
country: Poland
facility: Investigational Site 4810
city: Krakow
country: Poland
facility: Investigational Site 4812
city: Lublin
country: Poland
facility: Investigational Site
city: Nadarzyn
country: Poland
facility: Investigational Site
city: Poznan
country: Poland
facility: Investigational Site
city: Siedlce
country: Poland
facility: Investigational Site
city: Staszow
country: Poland
facility: Investigational Site
city: Warszawa
country: Poland
facility: Investigational Site 4811
city: Warszawa
country: Poland
facility: Investigational Site 4815
city: Wroclaw
country: Poland
facility: Investigational Site
city: Zamosc
country: Poland
facility: Investigational Site 4801
city: Zamosc
country: Poland
facility: Investigational Site 4816
city: A Coruna
country: Spain
facility: Investigational Site
city: Barcelona
country: Spain
facility: Investigational Site 3406
city: Barcelona
country: Spain
facility: Investigational Site 3407
city: Madrid
country: Spain
facility: Investigational Site 3402
city: Madrid
country: Spain
facility: Investigational Site 3410
city: Mostoles
country: Spain
facility: Investigational Site
city: Sabadell
country: Spain
facility: Investigational Site
city: Santiago de Compostela
country: Spain
facility: Investigator Site
city: Sevilla
country: Spain
facility: Investigational Site
city: Villajoyosa
country: Spain
facility: Investigational site
city: Barnsley
country: United Kingdom
facility: Investigational Site
city: Blackpool
country: United Kingdom
facility: Investigational Site
city: Leeds
country: United Kingdom
facility: Investigational Site 4401
city: Leeds
country: United Kingdom
facility: Investigational Site 4410
city: Liverpool
country: United Kingdom
facility: Investigational Site
city: Manchester
country: United Kingdom
facility: Investigational Site
city: Middlesex
country: United Kingdom
facility: Investigational Site
city: North Shields
country: United Kingdom
facility: Investigational Site
city: Romford
country: United Kingdom
facility: Investigational Site
Study officials:
affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK
name: Philip Conaghan, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: