E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Pain resulting from swollen joints |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073925 |
E.1.2 | Term | Generalised osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigate the effects of ONO-4474 on walking pain |
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E.2.2 | Secondary objectives of the trial |
Investigate the effects of ONO-4474 on knee pain, stiffness and function Investigate the effects of ONO-4474 on functional health status and quality of life Investigate the use of rescue medication Evaluate the safety and tolerability of ONO-4474 Evaluate the PK of ONO-4474
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female (of non-childbearing potential) aged between 40 – 75 years inclusive at the time of signing the informed consent form 2. Symptomatic OA of the knee for ≥3 months diagnosed prior to screening as per American College of Rheumatology clinical criteria 3. Radiographic evidence of tibiofemoral OA of index knee (Kellgren-Lawrence grade 2-3), as confirmed at screening 4. Moderate to severe index knee pain due to OA requiring use of analgesic medication 5. Willing to discontinue use of all analgesic medication (aside from rescue medication) during the study
Other inclusion criteria will also be applied. |
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E.4 | Principal exclusion criteria |
1. Presence of, or history of, a. 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) b. RPOA, osteonecrosis, osteoporotic fracture or any other painful joint disease other than OA c. Secondary causes of OA; other rheumatologic or musculoskeletal conditions (e.g., rheumatoid arthritis, fibromyalgia, septic arthritis, congenital abnormality) 2. 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 3. Symptomatic hip OA 4. A history of partial or complete joint replacement surgery in the index knee at any time or anticipating knee surgery during the study period 5. Significant knee injury or any knee surgery (including arthroscopy) in the index knee within 6 months prior to screening 6. Patients with uncontrolled diabetes
Other exclusion criteria will also be applied. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Week 4 in mean daily average index knee pain while walking (24h recall) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline to: • Weeks 1, 2 and 3, and over 4 weeks in mean daily average index knee pain while walking (24h recall) • Weeks 1, 2 and 4, and over 4 weeks in WOMAC pain, stiffness and physical function scores (48h recall) • Weeks 1, 2 and 4, and over 4 weeks in overall WOMAC score (48h recall) • Weeks 1, 2, 3 and 4, and over 4 weeks in mean daily average index knee pain (24h recall) Change from baseline to Weeks 1, 2 and 4, and over 4 weeks in Patient Global Assessment (PGA) Improvement score on Weeks 1, 2 and 4, and over 4 weeks in Clinical Global Impression (CGI) Change from baseline to Week 4 in EuroQoL EQ-5D-5L Use of rescue medication as a total number of tablets taken at Weeks 1, 2, 3 and 4 Time to first rescue medication use Safety profile as assessed by physical examination (including weight and height [height screening only]), vital signs, 12-lead electrocardiogram (ECG), safety laboratory evaluations, C-SSRS, adverse events, neurological examination Ctrough of ONO-4474 in plasma collected pre-dose at Visits 4, 5 and 7
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 1, 2, 3, 4 and over 4 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 27 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 27 |