E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | PT |
E.1.2 | Classification code | 10031161 |
E.1.2 | Term | Osteoarthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
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 |
To demonstrate the efficacy of at least one dose (among 3 doses) of S201086 compared to placebo after 52 weeks of treatment in reducing cartilage loss measured by cartilage thickness using quantitative magnetic resonance imaging (qMRI) of the central medial tibiofemoral compartment (cMTFC) of the target knee. |
Demostrar la eficacia de al menos una dosis (entre 3 dosis) de S201086 en comparación con el placebo, tras 52 semanas de tratamiento, en la reducción de la pérdida de cartílago medida por el grosor del cartílago mediante imagen de resonancia magnética cuantitativa (RMc) del compartimento tibiofemoral medial central (CTFMc) de la rodilla afectada |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of 3 doses of S201086 To assess efficacy of 3 doses of S201086 versus placebo after 52 weeks of treatment on: - the proportion of structural progressors based on cartilage thickness using qMRI of the cMTFC of the target knee - pain, function, and stiffness measured with WOMAC - pain measured with a 100-mm VAS - patient global assessment (PGA) of disease activity measured with 100-mm VAS - reduction of cartilage loss measured by cartilage thickness using qMRI of the total tibiofemoral compartment (tTFC) of the target knee - Joint Space Width (JSW) measured by x-ray To assess efficacy of 3 doses of S201086 versus placebo after 28 and 52 weeks of treatment on bone area using qMRI of the medial femoral condyle surface of the target knee To assess the pharmacokinetics of S201086 To assess efficacy of 3 doses of S201086 versus placebo after 52 weeks of treatment on analgesic consumption |
Evaluar la seguridad y tolerabilidad de 3 dosis de S201086. Evaluar la eficacia de 3 dosis de S201086 frente al placebo tras 52 semanas de tratamiento en: la proporción de pacientes con empeoramiento estructural basado en el grosor del cartílago con una RMc del CTFMc de la rodilla afectada, el dolor, la funcionalidad y la rigidez medidos con la escala WOMAC, el dolor medido con una escala visual analógica de 100 mm, la evaluación global del paciente de la actividad de la enfermedad medida con una EVA de 100 mm la reducción de la pérdida de cartílago medida por el grosor del cartílago con una RMc del compartimento tibiofemoral total de la rodilla afectada la anchura del espacio articular determinado con radiografía Evaluar la eficacia en cuanto a área ósea con una RMc de la superficie condílea femoral medial de la rodilla afectada Evaluar la farmacocinética de S201086 Evaluar la eficacia en cuanto a consumo de analgésicos |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male patients or female patients of non-childbearing potential Age between 40 to 75 years (both inclusive) Body weight > 40 kg, body mass index (BMI) < 40 kg/m2 Diagnosed for knee osteoarthritis based on clinical and radiological criteria of the American College of Rheumatology History of knee pain for at least 6 months and on the majority of days (> 50%) during the preceding month Symptoms severity defined by a pain ≥ 40 mm and ≤ 90 mm on VAS (100 mm) Documented need for symptomatic as needed-treatment for OA in the target knee with systemic non-steroidal anti-inflammatory drugs (NSAIDs) and/or other analgesics |
Pacientes hombres o mujeres sin potencial reproductivo De entre 40 y 75 años de edad (ambos inclusive) Peso corporal > 40 kg, un índice de masa corporal (IMC) < 40 kg/m2 Con diagnóstico de artrosis de rodilla según los criterios clínicos y radiológicos del Colegio Americano de Reumatología Con antecedentes de dolor de rodilla de al menos 6 meses de evolución y la mayoría de los días (> 50 %) del mes anterior Con una intensidad ≥ 40 mm y ≤ 90 mm en la EVA (100 mm). Con necesidad documentada de tratamiento sintomático a demanda para la OA de la rodilla afectada con antiinflamatorios no esteroideos (AINE) sistémicos y/u otros analgésicos |
|
E.4 | Principal exclusion criteria |
Severe clinical knee malalignment according to the investigator Knee prosthesis already implanted (< 1 year) or not well-tolerated (contralateral side) Knee prosthesis already foreseen within the study period (whichever side) Hip prosthesis recently implanted (< 1 year) or foreseen within the study period (whichever side) Previous osteotomy on the inferior limbs (whichever side) Surgical operation on the target knee within the 12 months prior to the screening visit or planned during the study Arthroscopy of the target knee within the 6 months prior to the screening visit or planned during the study Other pathologies affecting the knee Any contraindication to MRI including the inability to undergo a knee MRI exam because of inability to fit in the scanner or knee coil |
Malignidad clínica severa en la rodilla a juicio del investigador Protesis de rodilla ya implantada (<1 año) o no bien tolerada (lado contralateral) Protesis de rodilla ya programada en el periodo del estudio (cualquier lado) Protesis de rodilla recientemente implantada (<1año) o ya programada en el periodo del estudio (cualquier lado) Osteotomía previa de miembros inferiores (cualquier lado) Operación quirúrgica de la rodilla afectada en los 12 meses previos a la visita de selección o programada durante el estudio Artroscopia de la rodilla afectada en los 6 meses previos a la visita de selección o programada durante el estudio Otras patologías que afecten la rodilla Cualquier contraindicación a la RM incluida la imposibilidad de realizar una prueba de RM de rodilla por no poder ajustarse al escáner o a la bobina de rodilla |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Cartilage thickness of the central medial tibiofemoral compartment (cMTFC) of the target knee |
Grosor del cartílago del compartimento tibiofemoral medial central de la rodilla afectada |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from baseline to W052 |
Cambio entre visita basal y S052 |
|
E.5.2 | Secondary end point(s) |
Efficacy endpoints: Proportion of structural progressors based on cartilage thickness of the cMTFC of the target knee WOMAC subscales scores of the target knee for pain, function and stiffness Pain of the target knee PGA of disease activity of the target knee Proportion of Outcome Measures in Rheumatology (OMERACT)-OARSI responders Cartilage thickness of the total tibiofemoral compartment (tTFC) of the target knee Bone area of the medial femoral condyle surface of the target knee JSW of the target knee Analgesic consumption
Safety endpoints: Adverse events Physical examination Body weight Vital signs Laboratory examinations ECG
Pharmacokinetic parameters of S201086 |
Criterios de eficacia: Proporción de pacientes con empeoramiento estructural según el grosor del cartílago del CTFMc de la rodilla afectada Variación en las puntuaciones de dolor, funcionalidad y rigidez en las subescalas WOMAC de la rodilla afectada Dolor de la rodilla afectada EGP de la actividad de la enfermedad en la rodilla afectada Proporción de pacientes con respuesta en OMERACT (Outcome Measures in Rheumatology)-OARSI Grosor de cartílago del compartimento tibiofemoral total (CTFt) de la rodilla afectada Zona ósea de la superficie condílea femoral medial de la rodilla afectada Anchura del EA de la rodilla afectada Consumo de analgésicos
Criterios de seguridad: Acontecimientos adversos Evaluación física Peso corporal Signos vitales Análisis de laboratorio ECG
Parámetros farmacocinéticos de S201086 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Proportion of structural progressors based on cartilage thickness of the cMTFC of the target knee, cartilage thickness of the tTFC of the target knee, bone area of the medial femoral condyle surface of the target knee : W000, W028, W052 WOMAC subscales scores, PGA of disease activity of the target knee, proportion of OMERACT-OARSI responders: W000, W012, W028, W040, W052 Pain of the target knee: ASSE, W000, W004, W008, W012, W020, W028, W040, W052 JSW of the target knee: ASSE, W052 Analgesic consumption: all over the study Adverse events, Physical examination, Vital signs, Laboratory examinations: all over the study Body weight: ASSE, W000, W012, W028, W052 ECG: ASSE, W000, W004, W028, W052 Pharmacokinetic parameters of S201086: W004, W012, W028, W040, W052 |
Proporción de pacientes con empeoramiento estructural según el grosor del cartílago del CTFMc , grosor de cartílago del CTFt , zona ósea de la superficie condílea femoral medial: S000, S028, S052 Puntuación de las subescalas WOMAC, EGP de la actividad de la enfermedad, proporción de pacientes con respuesta en OMERACT–OARSI: S000, S012, S028, S040, S052 Dolor: ASSE, S000, S004, S008, S012, S020, S028, S040, S052 Anchura del espacio articular: ASSE, S052 Consumo de analgésicos: durante todo el estudio Acontecimientos adversos, evaluación física, signos vitales, análisis de laboratorio: durante todo el estudio Peso corporal: ASSE, S000, S012, S028, S052 ECG: ASSE, S000, S004, S028, S052 Parámetros farmacocinéticos de S201086/GLPG197: S004, S012, S028, S040, S052 |
|
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Bulgaria |
Canada |
Denmark |
Hungary |
Japan |
Korea, Democratic People's Republic of |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
Last visit last patient |
Ultima visita del ultimo paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |