E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoarthritic Pain |
Dolor por artrosis |
|
E.1.1.1 | Medical condition in easily understood language |
Pain resulting from swollen joints |
Dolor debido a la inflamación de las articulaciones |
|
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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073925 |
E.1.2 | Term | Generalised osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
|
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 |
Investigar los efectos de ONO-4474 sobre el dolor al caminar |
|
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 |
Investigar los efectos de ONO-4474 sobre el dolor, la rigidez y la funcionalidad de la rodilla Investigar los efectos de ONO-4474 sobre el estado de salud funcional y la calidad de vida Investigar el uso de medicamentos de rescate Evaluar la seguridad y tolerabilidad de ONO-4474 Evaluar la farmacocinética (FC) de ONO-4474 |
|
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. |
1. Hombre o mujer (sin capacidad de quedarse embarazada) con edad comprendida entre los 40-75 años (ambos incluidos) en el momento de firmar el formulario de consentimiento informado 2. Gonartrosis sintomática durante ≥3 meses que se haya diagnosticado antes de la selección según los criterios clínicos del Colegio Americano de Reumatología [American College of Rheumatology] 3. Prueba radiológica de gonartrosis femorotibial en la rodilla de referencia (Kellgren-Lawrence, grado 2-3), confirmada en la selección 4. Dolor moderado o grave en la rodilla de referencia por gonartrosis, que requiere el uso de analgésicos 5. Disposición a interrumpir el uso de analgésicos (excepto los medicamentos de rescate) durante el estudio
Se aplicarán otros criterios de inclusión. |
|
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. |
Antecedentes o existencia de: a. Cualquier tipo de artritis inflamatoria (p. ej., gota, artritis reactiva, artropatía soriática, espondiloartropatía seronegativa, artritis séptica, diagnóstico previo de seudogota en la articulación objeto del estudio con presencia de cristales en la aspiración articular o nivel elevado de proteína C-reactiva [PCR] en el momento de exacerbación de la gonartrosis) b. Artrosis rápidamente destructiva (RPOA), osteonecrosis, fractura osteoporótica o cualquier otra artropatía que cause dolor, además de la artrosis c. Causas secundarias de la artrosis; otras enfermedades reumáticas o del aparato locomotor (p. ej., artritis reumatoide, fibromialgia, artritis séptica o anomalías congénitas) 2. Cirugía ortopédica de las extremidades inferiores, cirugía mayor durante los 6 meses anteriores a la visita 1 o intervención quirúrgica prevista durante el estudio 3. Coxartrosis sintomática 4. Cirugía de reemplazo articular parcial o completo en la rodilla de referencia en cualquier momento previo al estudio o cirugía de rodilla prevista durante el periodo del estudio 5. Lesión de rodilla significativa o cualquier tipo de cirugía de rodilla (incluida la artroscopia) en la rodilla de referencia durante los 6 meses anteriores a la selección 6. Pacientes con diabetes no controlada Se aplicarán otros criterios de exclusión. |
|
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) |
Cambio desde el inicio hasta la semana 4 en el promedio del dolor medio diario en la rodilla de referencia al caminar (recuerdo a las 24 h) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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 |
Cambio desde el inicio: • Hasta las semanas 1, 2 y 3, y durante 4 semanas en el promedio del dolor medio diario en la rodilla de referencia al caminar (recuerdo a las 24 h) • Hasta las semanas 1, 2 y 4, y durante 4 semanas en las puntuaciones de dolor, rigidez y función física según la escala de dolor de la artrosis de las Universidades de Western Ontario y McMaster (WOMAC) (recuerdo a las 48 h) • Hasta las semanas 1, 2 y 4, y durante 4 semanas en la puntuación total de la escala WOMAC (recuerdo a las 48 h) • Hasta las semanas 1, 2, 3 y 4, y durante 4 semanas en el promedio del dolor medio diario en la rodilla de referencia (recuerdo a las 24 h) Cambio desde el inicio hasta las semanas 1, 2 y 4, y durante 4 semanas en la Evaluación Global del Paciente (PGA) Mejora de la puntuación en las semanas 1, 2 y 4, y durante 4 semanas en la Impresión Clínica Global (CGI) Cambio desde el inicio hasta la semana 4 en el cuestionario EuroQoL EQ-5D-5L Uso de medicamentos de rescate como número total de comprimidos tomados en las semanas 1, 2, 3 y 4 Tiempo transcurrido hasta el primer uso de medicamentos de rescate Evaluación del perfil de seguridad mediante una exploración física (incluidos el peso y la talla [esta última solo en la selección]), constantes vitales, electrocardiograma (ECG) de 12 derivaciones, analíticas de seguridad, Escala Columbia para evaluar la seriedad de la ideación suicida (C-SSRS), acontecimientos adversos y exploración neurológica Cmín de ONO-4474 en plasma obtenida antes de administrar la dosis en las visitas 4, 5 y 7 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 1, 2, 3, 4 and over 4 weeks |
Semanas 1, 2, 3, 4, y durante 4 semanas |
|
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 | 11 |
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
|
LVLS |
Última visita del último paciente |
|
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 |