E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Sclerosis (MS) |
Esclerosis Múltiple (EM) |
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E.1.1.1 | Medical condition in easily understood language |
Multiple Sclerosis (MS) |
Esclerosis Múltiple (EM) |
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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 | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
The primary objective is to assess the long term safety of GNbAC1 in patients with RRMS. |
El objetivo principal es evaluar la seguridad a largo plazo de GNbAC1 en pacientes con esclerosis múltiple recidivante-remitente. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the long-term efficacy of GNbAC1 in terms of MRI outcomes, relapse rate, disability and disease progression. |
Los objetivos secundarios son evaluar la eficacia a largo plazo de GNbAC1 basándose en los resultados de las RM, la tasa de recidivas, la incapacidad y la progresión de la enfermedad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients must have completed Period 2 of study GNC-003 and must meet all eligibility criteria for the GNC-004 study; - Patients (male or female with reproductive potential) must agree to use highly effective methods of birth control |
- Pacientes que hayan finalizado el Período 2 del estudio GNC-003 y que cumplan todos los criterios de selección para el estudio GNC-004; - Los pacientes (de ambos sexos que sean potencialmente fértiles) deben estar de acuerdo en el uso de métodos anticonceptivos altamente eficaces |
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E.4 | Principal exclusion criteria |
- Patients not having completed study GNC-003. - Emergence of any disease diagnosis during the course of study GNC-003 that is not MS and could better explain the patient’s neurological signs and symptoms. - Any major medical or psychiatric disorder that could put the patient at undue risk during the study, according to the investigator’s opinion, or that would affect the capacity of the patient to fulfill the requirements of the study, including: Schizophrenia, bipolar disorder, or major depressive disorder, History of suicide attempt, or current suicidal ideation, current alcohol or drug abuse. - Body weight<40kg - Patients not able to follow study instructions, or not able to follow the study assessments defined by the protocol. - Forbidden concomitant treatments - Legal incapacity or limited legal capacity. - Pregnancy. - Female patients of childbearing potential (FPCBP) or procreative male patients (PMP), not willing to use highly effective contraceptive methods throughout the study duration and at least until 5 months after the last study treatment. |
- Pacientes que no hayan finalizado el estudio GNC-003; - Cualquier enfermedad distinta de MS durante el estudio GNC-003 que pudiera explicar mejor los signos y síntomas neurológicos del paciente; - Cualquier trastorno médico o psiquiátrico de índole mayor que, a criterio del investigador, pudiera comportar un riesgo indebido para el paciente durante el estudio o que pudiera afectar la capacidad del paciente para cumplir los requisitos del estudio, como: esquizofrenia, trastorno bipolar o trastorno depresivo mayor, antecedentes de intentos de suicidio o ideas suicidas actuales; abuso actual de alcohol o de drogas; - Peso corporal <40 kg - Pacientes que no sean capaces de seguir las instrucciones del estudio o las evaluaciones del estudio definidas en el protocolo; - Tratamientos concomitantes prohibidos - Incapacidad legal o limitación de la capacidad legal; - Embarazo; - Mujeres o varones potencialmente fértiles que no estén dispuestos a utilizar métodos anticonceptivos altamente eficaces durante todo el estudio y al menos hasta 5 meses después del último tratamiento del estudio; |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following parameters will be evaluated to assess the long term safety of GNbAC1: - Spontaneously-reported adverse events (AEs) and serious adverse events (SAEs); - Clinical safety laboratory (Haematology, Chemistry, Coagulation) and urine pregnancy test; - IgG4 dosing; - Physical examination and vital signs: Blood pressure, heart rate, temperature, and body weight; - 12-lead ECG; - Human anti-GNbAC1 antibodies in serum; - Suicidality assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). |
Los siguientes parámetros serán evaluados para evaluar la seguridad a largo plazo de GNbAC1: - Acontecimientos adversos comunicados espontáneamente en cada visita y acontecimientos adversos graves - Analítica de seguridad (hematología, bioquímica, coagulación), y prueba de embarazo en orina - Determinación de IgG4 - Exploración física y constantes vitales: presión arterial, frecuencia cardíaca, temperatura y peso corporal, - ECG de 12 derivaciones - Anticuerpos humanos anti-GNbAC1 en suero - Evaluación de las tendencias suicidas con la Columbia Suicide Severity Rating Scale (C-SSRS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- AEs at each visit; SAEs at any time - Laboratory parameters every 6 months and urine pregnancy test at each study visit - Physical examination and vital signs at selection and at each study visit - C-SSRS at every visit - ECG and human anti-GNbAC1 antibodies every 6 months - IgG4 at baseline, W48 and W96 |
- Acontecimientos adversos comunicados espontáneamente en cada visita y acontecimientos adversos graves comunicados en cualquier momento; - Analítica de seguridad cada 6 meses y prueba de embarazo en orina en cada visita del estudio; - Exploración física y constantes vitales en la inclusión y en cada visita del estudio; - C-SSRS en cada visita. - ECG y anticuerpos humanos anti-GNbAC1 cada 6 meses. - Determinación de IgG4 en el punto temporal basal, S48 y S96 |
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E.5.2 | Secondary end point(s) |
The following parameters will be evaluated to assess the long term efficacy of GNbAC1: - Brain MRI markers of inflammation, disease progression, demyelination and remyelination; - Annualized relapse rate; - Proportion of patients with confirmed neurological disability worsening (defined as an increase of ≥ 1.5 step on the EDSS for EDSS= 0; increase of ≥ 1 step on the EDSS from EDSS > 0 and < 5.5; and ≥0.5 EDSS steps from EDSS ≥ 5.5, confirmed after at least 3 months at scheduled clinic visits) - Proportion of patients with confirmed neurological disability improvement (defined as a decrease of at least 1 step on the EDSS from EDSS ≥1 and < 5.5and decrease of at least 0.5 EDSS steps from EDSS ≥ 5.5, confirmed after at least 3 months at scheduled clinic visits) - Proportion of patients with No Evidence of Disease Activity (NEDA, defined as absence of new T1 or T2 lesions on MRI scan, absence of relapse and absence of confirmed disability worsening at Week 48 and 96); - Time to confirmed neurological disability worsening (as defined above); - Time to confirmed neurological disability improvement (as defined above); - EDSS change from baseline in GNC-003 study; - MSFC scores (including subcomponent scores) change from baseline in GNC-003 study. |
Los siguientes parámetros serán evaluados para evaluar la eficacia a largo plazo de GNbAC1: - En la RM cerebral, marcadores de inflamación, progresión de la enfermedad, desmielinización y remielinización: - Tasa anualizada de recidivas - Porcentaje de pacientes con empeoramiento confirmado de la incapacidad neurológica (definido como aumento de ≥ 1,5 puntos en la EDSS para EDSS = 0; aumento de ≥ 1 punto en la EDSS desde EDSS > 0 a < 5,5; y de ≥ 0,5 puntos en la EDSS desde EDSS ≥ 5,5, confirmado después de al menos 3 meses en las visitas clínicas programadas) - Porcentaje de pacientes con mejoría confirmada de la incapacidad neurológica (definida como disminución de al menos 1 punto en la EDSS desde EDSS ≥1 a < 5,5 y disminución de al menos 0,5 puntos en la EDSS desde EDSS ≥ 5,5, confirmada después de al menos 3 meses en las visitas clínicas programadas) - Porcentaje de pacientes sin indicios de actividad de la enfermedad (No Evidence of Disease Activity, NEDA), lo que se define como ausencia de nuevas lesiones en T1 o T2 en la RM, ausencia de recidivas y ausencia de empeoramiento confirmado de la incapacidad en la Semana 48 y la Semana 96 del estudio GNC-004) - Tiempo hasta el empeoramiento confirmado de la incapacidad neurológica (según la definición anterior); - Tiempo hasta la mejoría confirmada de la incapacidad neurológica (según la definición anterior); - Cambio en el EDSS, entre el punto temporal basal del estudio GNC-003 - Cambio en la puntuación del complejo funcional de esclerosis múltiple (MSFC) (incluidas puntuaciones de subcomponentes) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Brain MRI at Weeks 48 and 96 - Annualized relapse rate from baseline in GNC-003 to Weeks 48 and from weeks 48 to weeks 96 - EDSS and MSFC at Weeks 24, 48, 72 and 96 - Proportion of patients with confirmed neurological disability worsening or improvement from baseline in GNC-003 study to weeks 24, 48, 72 and 96 |
- RM cerebral y las Semanas 48 y 96 - Tasa anualizada de recidivas, entre el punto temporal basal del estudio GNC-003 y la Semana 48 del estudio GNC-004 y entre las semanas 48 y 96; - EDSS y MSFC y las Semanas 24, 48, 72 y 96 - Porcentaje de pacientes con empeoramiento confirmado de la incapacidad neurológica entre el punto temporal basal del estudio GNC-003 y las Semanas 24, 48, 72 y 96; |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, biomarkers analysis |
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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 | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Bulgaria |
Croatia |
Czech Republic |
Estonia |
Germany |
Hungary |
Italy |
Poland |
Russian Federation |
Serbia |
Spain |
Ukraine |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |