E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progressive supranuclear palsy |
Parálisis supranuclear progresiva |
|
E.1.1.1 | Medical condition in easily understood language |
A rare and progressive condition that can cause problems with balance, movement, vision, speech and swallowing |
Enfermedad rara y progresiva que causa problemas de equilibrio, movilidad, visión, habla y deglución |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036813 |
E.1.2 | Term | Progressive supranuclear palsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of BMS-986168, compared to placebo, as measured by a change from baseline in the PSP Rating Scale (PSPRS) at Week 52.
To assess the safety and tolerability of BMS-986168, relative to placebo, by measuring the frequency of deaths, SAEs, AEs leading to discontinuation, and Grade 3 & 4 laboratory abnormalities. |
Evaluar la eficacia de BMS-986168 en comparación con un placebo midiendo el cambio con respecto al inicio en la escala de valoración de la PSP (PSPRS) en la semana 52.
Evaluar la seguridad y la tolerabilidad de BMS-986168 en comparación con el placebo midiendo la frecuencia de muertes, AAGs, AAs que conlleven la interrupción del tratamiento y anomalías en las pruebas de laboratorio de grado 3 y 4. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of BMS-986168, compared to placebo, as measured by: - a change in baseline in the MDS-UPDRS Part II at Week 52. - the CGI-C at Week 52. - a change in baseline in the RBANS at Week 52. - a change from baseline at Week 48 (Week 52 for CGI-S) on the following instruments: - SEADL Scale - CGI-S - Phonemic Fluency Test - Letter-Number Sequencing Test - Color Trails Test - MoCA
To assess the impact of BMS-986168 on quality of life, relative to placebo, as measured by change from baseline on the PSP-QoL scale at Week 52.
To assess the immunogenicity of BMS-986168.
To assess the efficacy of BMS-986168, relative to placebo, as measured by absolute and percent change from baseline of brain volumes, as determined by MRI, at Week 52 in the following regions: - Ventricles - Whole brain - Midbrain - Superior cerebellar peduncle - Third ventricle - Frontal lobe |
Evaluar eficacia BMS-986168 respecto placebo midiendo : -cambio respecto inicio en parte II de revisión escala valoración unificada enfermedad Parkinson (UPDRS) promovida por Sociedad trastornos movimiento (MDS-UPDRS) en sem 52 -impresión clínica global cambio (CGI-C) en sem 52 -cambio respecto inicio en RBANS sem 52 -cambio respecto inicio en sem 48 (sem 52 para CGI-S) en: - Escala actividades vida diaria Schwab y England-SEADL - CGI-S - Prueba fluidez fonémica, secuenciación letras-números, rastros de color - Evaluación cognitiva Montreal (MoCA) -Evaluar efecto BMS-986168 en calidad vida respecto placebo midiendo cambio respecto inicio en PSP-QoL en sem 52 -Evaluar inmunogenia BMS-986168 -Evaluar eficacia BMS-986168 en respecto placebo midiendo cambio absoluto y porcentual respecto inicio en sem 52 según determinado por RM en los volúmenes cerebrales siguientes : Ventrículos, todo el cerebro, mesencéfalo, pedúnculo cerebeloso superior, tercer ventrículo, lóbulo frontal |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Participants with probable or possible PSP • Able to ambulate independently or with assistance • Able to tolerate MRI • Have reliable caregiver to accompany participant to all study visits • Score greater or equal to 20 on the Mini Mental State Exam (MMSE) at screening • Participant must reside outside a skilled nursing facility or dementia care facility at the time of screening and admission to such a facility must not be planned |
-Participante con PSP probable o posible. -Capaz de deambular con independencia o con ayuda. -Capaz de tolerar una RM. -Que cuenta con un cuidador fiable que lo acompaña a todas las visitas del estudio. -Con una puntuación igual o superior a 20 en el Miniexamen del Estado Mental (MMSE) en la selección. -El participante debe residir fuera de un centro especializado de enfermería o de un centro de atención a personas con demencia en el momento de la selección y no debe estar previsto su ingreso en un centro de ese tipo. |
|
E.4 | Principal exclusion criteria |
• Presence of other significant neurological or psychiatric disorders • Diagnosis of amyotrophic lateral sclerosis (ALS) or other motor neauron disease • History of early, prominent rapid eye movement (REM) sleep behaviour disorder • History of or screening brain MRI scan indicative of significant abnormality • Known history of serum or plasma progranulin level less than one standard deviation below the normal patient mean for the laboratory performing the assay |
-Presencia de otros trastornos psiquiátricos o neurológicos importantes. -Diagnóstico de esclerosis lateral amiotrófica (ELA) u otras enfermedades de la motoneurona. -Antecedentes de trastorno del comportamiento del sueño de movimientos oculares rápidos (REM) precoz e importante. -Antecedentes o RM cerebral en la selección indicativos de anomalías significativas. -Antecedentes conocidos de concentración plasmática o sérica de progranulina menor que una desviación estándar inferior a la media del valor de paciente normal para el laboratorio que realiza el análisis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in PSP (Progressive Supranuclear Palsy) Rating Scale 2. Frequency of Adverse Events |
1. Cambio en la escala de valoración de la PSP (PSPRS) 2.Frecuencia de Acontecimientos Adversos |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 52 weeks |
Hasta 52 semanas |
|
E.5.2 | Secondary end point(s) |
1. Change in Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDSUPDRS) Part II. 2. Impact of on the Clinical Global Impression of Change (CGI-C) scale score . 3. Impact on the Repeatable Battery for the Assessment of Neuropsychological Disease Severity (RBANS) scale. 4. Impact on the Progressive Supranuclear Palsy Quality of Life scale (PSP-QoL) scale. 5. Impact on the following instruments: - Schwab and England Activities of Daily Living (SEADL) Scale - Clinical Global Impression of Severity (CGI-S) - Phonemic Fluency Test - Letter-Number Sequencing Test - Color Trails Test - Montreal Cognitive Assessment (MoCA). 6. Immunogenicity by assessment of the presence or absence of specific drug antibodies (anti-BMS-986168) in serum. 7. Impact on brain volumes, as determined by MRI. |
1. Cambio en la parte II de la revisión de la escala de valoración unificada de la enfermedad de Parkinson (UPDRS) promovida por la Sociedad de trastornos del movimiento (MDS-UPDRS) 2. Efecto en la puntuación de la escala de impresión clínica global de cambio (CGI-C) 3. Efecto en la escala de la batería repetible para la evaluación de la gravedad de la enfermedad neuropsicológica (RBANS) 4. El efecto en la escala de calidad de vida de la parálisis supranuclear progresiva (PSP-QoL) 5. El efecto en los instrumentos siguientes: - Escala de actividades de la vida diaria de Schwab y England (SEADL). - Impresión clínica global de la gravedad (CGI-S). - Prueba de fluidez fonémica. - Prueba de secuenciación de letras y números. - Prueba de rastros de color. - Evaluación cognitiva de Montreal (MoCA). 6. La inmunogenia se evaluará midiendo la presencia o ausencia de anticuerpos específicos contra el fármaco (anti-BMS-986168) en el suero. 7. El efecto según lo determinado por la RM en los volúmenes cerebrales |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All - screening and Week 52. Except: - Scale, Phonemic Fluency Test, Letter-Number Sequencing Test, Color Trails Test and MoCA - screening and Week 48. - Immunogenicity - Day 1, Weeks 4, 8, 12, 24, 36 and 48 then at 24 week intervals during the open-label period. |
Todos: selección y Semana 52. Excepto: - Escala, Prueba de Fluidez Fonética, Prueba de Secuenciación de Letras y Números, Prueba de Rastros de Color y Evaluación Cognitiva de Montreal (MoCA): selección y Semana 48.
- Inmunogenia: Día 1, Semanas 4, 8, 12, 24, 36 y 48 y después a intervalos de 24 semanas durante el periodo en abierto. |
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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 | Yes |
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 | 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 |
Immunogenicity, biomarker analysis |
Inmunogenia y análisis de biomarcadores |
|
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 | Yes |
E.8.1.7.1 | Other trial design description |
Periodo de tratamiento en doble ciego seguido de una fase de extensión de tratamiento abierta. |
Double-blind treatment period followed by an open-label extension period |
|
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Austria |
Canada |
France |
Germany |
Greece |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Russian Federation |
Spain |
United Kingdom |
United States |
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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
|
The date that the last participant completes the last study visit or scheduled procedure, will be defined as the end of the study. |
Se definirá como fin del estudio la fecha en que el último participante complete la última visita del estudio o el último procedimiento programado. |
|
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 | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |