E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Knee osteoarthritis |
Osteoartritis de rodilla (OA) |
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E.1.1.1 | Medical condition in easily understood language |
Knee osteoarthritis |
Osteoartritis de rodilla |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee 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 |
To assess efficacy of QUC398 vs placebo in relieving OA pain in the target knee |
Evaluar la eficacia de QUC398 frente a placebo para aliviar el dolor de la OA en la rodilla estudiada |
|
E.2.2 | Secondary objectives of the trial |
•To assess the efficacy of QUC398 vs placebo in preservation of cartilage in the medial compartment of the target knee •To assess the efficacy of QUC398 vs placebo in relieving OA pain in the target knee over time •To assess the efficacy of QUC398 vs placebo in relieving clinical symptoms and improving function in the target knee over time •To assess the safety and tolerability of QUC398 vs placebo. |
- Evaluar la eficacia de QUC398 frente a placebo para la preservación del cartílago en el compartimento medial de la rodilla estudiada. - Evaluar la eficacia de QUC398 frente a placebo para aliviar el dolor de la OA en la rodilla estudiada a lo largo del tiempo. - Evaluar la eficacia de QUC398 frente a placebo para aliviar los síntomas clínicos y mejorar la función en la rodilla estudiada a lo largo del tiempo. - Evaluar la seguridad y la tolerabilidad de QUC398 frente a placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Weight >/= 50 kg and a body mass index (BMI) between 18 -35 kg/m2, at Screening 1 •Kellgren-Lawrence grade 2 to 4 in the tibio-femoral compartment in the target knee confirmed by radiography in standing weight-bearing fixed flexion position and posterior-anterior view, at Screening 1 •Radiographic medial joint space width (mJSW) of 2 to 4 mm in men or 1.5 to 3.5 mm in women measured at the X=0.225 fixed point location within the medial tibio-femoral compartment of the target knee at Screening 1 •Symptomatic OA with moderate to severe pain (corresponding to Pain NRS >/= 5 to </= 9) in the target knee for the majority of days in the last 3 months prior to Screening 1, as per participant's judgement •Symptomatic OA with moderate to severe pain (corresponding to Pain NRS >/= 5 to </= 9) in the target knee at Screening 1 and 2. •Moderate to severe OA pain (corresponding to Pain NRS >/= 5 to </= 9) in the target knee during the last 7 days prior to Screening 3, confirmed by: - Completed pain diary for at least 6 of the last 7 days prior to Screening 3 AND - Diary reported Pain NRS >/= 5 to </= 9 for at least 6 of the last 7 days prior to Screening 3 • KOOS pain subscale </= 60 in the target knee at Screening 1, Screening 2, and Screening 3.
Additional protocol specified criteria may apply. |
• Peso >/=50 kg e índice de masa corporal (IMC) entre 18 y 35 kg/m2 en la selección 1. • OA en el compartimento tibiofemoral de la rodilla estudiada de grado de 2 a 4 en la escala de Kellgren-Lawrence confirmada mediante una radiografía con carga en flexión fija en bipedestación y con vista anteroposterior en la selección 1. • Anchura del espacio articular medial (mJSW) de 2 a 4 mm en hombres o de 1,5 a 3,5 mm en mujeres confirmada mediante una radiografía y medida en el punto fijo X = 0,225 del compartimento tibiofemoral medial de la rodilla estudiada en la selección 1. • OA sintomática con dolor de moderado a grave (correspondiente a >/=5 e </=9 en la escala numérica del dolor) en la rodilla estudiada la mayoría de días en los 3 meses anteriores a la selección 1 según el criterio del participante. • OA sintomática con dolor de moderado a grave (correspondiente a >/=5 e </=9 en la escala numérica del dolor) en la rodilla estudiada en la selección 1 y 2. • OA con dolor de moderado a grave (correspondiente a >/=5 e </=9 en la escala numérica del dolor) en la rodilla estudiada durante los 7 días anteriores a la selección 3 confirmada mediante: • Diario para notificar el dolor cumplimentado durante al menos 6 de los 7 días anteriores a la selección 3 Y • Escala numérica del dolor >/=5 e </=9 notificada en el diario durante al menos 6 de los 7 días anteriores a la selección 3. • Subescala KOOS del dolor </=60 en la rodilla estudiada en la selección 1, selección 2 y selección 3. Pueden aplicarse criterios adicionales especificados en el protocolo. |
|
E.4 | Principal exclusion criteria |
•Painful ipsilateral hip OA defined as a Pain NRS >/3 on the majority of days in the last 3 months prior to Screening 1, as reported by the patient. •Symptomatic, patello-femoral pain in the target knee as per investigator's examination at Screening 1. •Severe malalignment > 7.5º in the target knee (either varus or valgus), measured using standardized knee X-ray at Screening 1. •Patient unable or unwilling to undergo MRI or presenting absolute contraindications to MRI. •Previous exposure to any ADAMTS-5 drug, including QUC398. •History or current diagnosis of ECG abnormalities.
Additional protocol specified criteria may apply. |
• OA dolorosa en la cadera ipsilateral definida como >/=3 en la escala numérica del dolor la mayoría de días en los 3 meses anteriores a la selección 1 según lo notificado por el paciente. • Dolor patelofemoral sintomático en la rodilla estudiada según la exploración realizada por el investigador en la selección 1. • Alineamiento defectuoso grave >7.5º en la rodilla estudiada (varo o valgo) medido mediante una radiografía estándar de rodilla en la selección 1. • El paciente no puede o no quiere someterse a una RM o presenta contraindicaciones determinantes para la RM. • Exposición previa a cualquier fármaco inhibidor de ADAMTS-5, incluido QUC398. • Antecedentes o diagnóstico actual de anomalías en el ECG. Pueden aplicarse criterios adicionales especificados en el protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12 |
Cambio respecto a la basal en la subescala del dolor Knee Injury and Osteoarthritis Outcome Score (KOOS) en la semana 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
•Change from baseline in cartilage volume of the knee index region at Week 52, as determined from the automated segmentation of 3D-MRI scans •Change from baseline in KOOS Pain subscale at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 •Change from baseline in pain assessed by a Pain Numerical Rating Scale (NRS) at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 •Change from baseline in total KOOS at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 •Change from baseline in KOOS subscales: Other symptoms, Function in daily living, Function in sport and recreation, and Knee related quality of life at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
•Change from baseline in Patient's Global Assessment (PGA) as assessed by NRS at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
•Systemic and local Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, Electrocardiogram parameters (ECGs), Vital signs, Laboratory tests |
- Cambio respecto a la basal en el volumen del cartílago en la zona de la rodilla afectada en la semana 52, según lo determinado a partir de la segmentación automática de RM en 3D. - Cambio respecto a la basal en la subescala del dolor KOOS en las semanas 1 (día 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 y 52. - Cambio respecto a la basal en el dolor evaluado mediante una escala numérica del dolor en las semanas 1 (día 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, y 52. - Cambio respecto a la basal en la puntuación total de la KOOS en las semanas 1 (día 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 y 52. - Cambio respecto a la basal en las subescalas KOOS (otros síntomas, función en la vida diaria, función en deporte y ocio y calidad de vida relacionada con la rodilla) en las semanas 1 (día 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 y 52. - Cambio respecto a la basal en la evaluación global del paciente (PGA) según la escala numérica en las semanas 1 (día 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 y 52. - Acontecimientos adversos aparecidos con el tratamiento (AAAT) sistémicos y locales y AAAT graves, parámetros electrocardiográficos (ECG), constantes vitales, pruebas analíticas |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As specified in the secondary endpoints |
Según se especifica en las evaluaciones secundarias. |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
|
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 | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Australia |
New Zealand |
United States |
France |
Spain |
Denmark |
Norway |
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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
|
Study completion is defined as when the last participant finishes their End of study (EOS) visit. |
La finalización del estudio se define cuando el último participante finaliza su visita de fin de estudio. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |