E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoarthritis of the Hip or Knee |
Artrosis de cadera o rodilla |
|
E.1.1.1 | Medical condition in easily understood language |
Osteoarthritis of the Hip or Knee |
Artrosis de cadera o rodilla |
|
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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020108 |
E.1.2 | Term | Hips 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 |
The primary objective is to demonstrate the efficacy using 2 co-primary endpoints (as measured by the changes from baseline to the end of Week 16 in the Western Ontario and McMaster University Osteoarthritis Index [WOMAC] pain and physical function subscales, and Patient Global Assessment [PGA] scores), safety, and tolerability of fulranumab subcutaneous (SC) injections as monotherapy compared with placebo in subjects with signs and symptoms of osteoarthritis of the hip or knee. |
El objetivo principal es demostrar la eficacia usando 2 criterios de valoración principales (según la medición de los cambios del inicio al fin de la semana 16 en las subescalas de dolor y función física del índice de artrosis WOMAC [Western Ontario and McMaster University Osteoarthritis Index]), la seguridad y la tolerabilidad de fulranumab en inyecciones subcutáneas (s.c.) como monoterapia en comparación con placebo en sujetos con signos y síntomas de artrosis de cadera o rodilla que no controlados adecuadamente con el tratamiento analgésico actual y que planifican una intervención quirúrgica de sustitución de articulación |
|
E.2.2 | Secondary objectives of the trial |
- Joint pain using Numerical Rating Scale (NRS) - Stiffness, sleep, functional status and well-being as perceived by the subject - Supplemental analgesic pharmacologic therapy use - Pharmacokinetics and immunogenicity of fulranumab |
- El dolor articular, mediante la escala de puntuación numérica (Numerical Rating Scale, NRS) - La rigidez, el sueño, el estado funcional y el bienestar, medidos por el sujeto - El uso adicional de analgésicos - La farmacocinética e inmunogenicidad de fulranumab |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Clinical diagnosis of osteoarthritis (OA) of hip or knee based on criteria defined by the American College of Rheumatology and radiographic evidence of OA (Kellgren-Lawrence class ?2) of the study joint -Scheduled joint replacement or planning to undergo a joint replacement surgery for the study joint -Must have an unsatisfactory response that includes at least one each of the following 3 classes of analgesic medications (acetaminophen/paracetamol, NSAIDs, and opioids) -Moderate to severe pain and functional impairment based on the NRS, WOMAC pain and physical function subscales, and PGA - During treatment and within 24 weeks after the last injection of study drug: if female of childbearing potential, is not pregnant, breast-feeding, or planning to become pregnant, or if male, will not father a child |
- Diagnóstico clínico de artrosis de cadera o rodilla basado en los criterios definidos por el American College of Rheumatology (Sociedad estadounidense de reumatología, o ACR) y pruebas radiográficas de artrosis (clase Kellgren-Lawrence ? 2) de la articulación estudiada -Tener planificado o programado someterse a artroplastia de la articulación en estudio. -Tener dolor e insuficiencia funcional de moderados a intensos basados en las subescalas de dolor y función física de la NRS, WOMAC y la PGA -Tener una respuesta no satisfactoria (eficacia inadecuada o mala tolerabilidad) que incluya al menos una de cada una de las siguientes 3 clases de analgésicos orales (paracetamol, AINE y un opioide). - Durante todo el estudio, desde la selección y hasta 24 semanas tras la última inyección del fármaco del estudio: si es mujer en edad fértil y no está embarazada, ni en periodo de lactancia o tiene intención de quedarse embarazada; o si es hombre, no debe tner intención de ser padre. |
|
E.4 | Principal exclusion criteria |
-Increased risk of osteonecrosis (ON) or rapidly progressive osteoarthritis (RPOA) -Unstable or progressive neurologic disorders |
- Un riesgo incrementado de RPOA o de osteonecrosis (ON) - La existencia de trastornos neurológicos inestables o progresivos |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Change from baseline to the end of Week 16 in Western Ontario and McMaster University Arthritis Index (WOMAC) pain subscale score - Change from baseline to the end of Week 16 in Western Ontario and McMaster University Arthritis Index (WOMAC) physical function subscale score |
- Cambio desde la visita basal hasta el final de la semana 16 en la subescala del dolor Western Ontario y McMaster Índice Artritis Universidad (WOMAC). - Cambio desde la visita basal hasta el final de la semana 16 en la subescalas de función física Western Ontario y McMaster Universidad Artritis Index (WOMAC). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, Week 16 |
Basal, semana 16 |
|
E.5.2 | Secondary end point(s) |
Change from baseline to the end of the 16-week double-blind phase in scores in: - WOMAC Stiffness subscale - Daily NRS scores - MOS Sleep subscales - SF-36 subscales - EQ-5D-5L - Patient Global Assessment (PGA) score |
Cambio del inicio al fin de la fase de doble ciego de 16 semanas en las puntuaciones de: - Subescala de rigidez WOMAC - Puntuaciones NRS diarias - Escala de sueño MOS - Subescalas de SF-36 - EQ-5D-5L - Evaluación global por el paciente (PGA) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints listed above in endpoints. |
Momento de evaluación de esta variable secundaria listada arriba en Variables de evaluación. |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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 | 60 |
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 |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Netherlands |
Poland |
Romania |
Spain |
United Kingdom |
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
|
LPLV |
Último paciente Última visita |
|
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 | 19 |
E.8.9.1 | In the Member State concerned days | 19 |
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 | 19 |
E.8.9.2 | In all countries concerned by the trial days | 19 |