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 | 18.1 |
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 |
To assess the efficacy of repeated doses of GNbAC1 in patients with MS based on the cumulative number of gadolinium (Gd)-enhancing T1 lesions on brain MRI vs. placebo. |
Evaluar la eficacia de dosis repetidas de GNbAC1 en pacientes con EM basándose en el número acumulado de lesiones potenciadas con gadolinio (Gd) en T1 en la RM cerebral, frente al placebo |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of GNbAC1 on other parameters of disease activity - To evaluate the safety and tolerability of repeated doses of GNbAC1 - To evaluate pharmacokinetics of repeated doses of GNbAC1 |
- Evaluar el efecto de GNbAC1 en otros paremetros de actividad de la enfermedad - Evaluar la seguridad y tolerabilida de dosis repetidas de GNbAC1 - Evaluar la farmacocinética de dosis repetidas de GNbAC1 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of relapsing remitting multiple sclerosis according to Mc Donald criteria (2010) - Evidence of recent disease activity: at least one documented relapse within the last 12 months and /or at least one Gd-enhancing T1 lesion at selection or evidenced within the last 3 months - Body weight > 40 kg and ? 100 kg - EDSS score < 6.0 - Patient (male or female with reproductive potential) who agree to use a highly effective method of birth control. -Other criteria as stated in study protocol |
- Diagnostico de EMRR de acuerdo con los criterios de McDonald revisados en 2010 - Evidencia de actividad de la enfermedad: por al menos una recidiva documentada en los últimos 12 meses, y/o al menos una lesión potenciada con Gd en T1 en la selección o en el plazo de los últimos 3 meses - Peso corporal > 40 kg y ? 100 kg - Puntuación de la EDSS < 6,0 - Pacientes (de ambos sexos que sean potencialmente fértiles) deben estar de acuerdo en el uso de métodos anticonceptivos altamente eficaces
Otros criterios de seleccion segun el protocolo |
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E.4 | Principal exclusion criteria |
- Patients suffering from secondary progressive MS (SPMS) or primary progressive MS (PPMS); - Any disease other than MS that could better explain signs and symptoms; - Complete transverse myelitis or bilateral optic neuritis; - Patients who have been treated with: oral or systemic corticosteroids, adrenocorticotropic hormone (ACTH), or fingolimod within 30 days prior to selection ; interferon beta or glatiramer acetate, intravenous immunoglobulin (IVIG), natalizumab, dimethylfumarate or teriflunomide in the last 3 months prior to selection ; mitoxantrone, alemtuzumab, cyclophosphamide, cytotoxic or immunosuppressive therapy (excluding systemic steroid and ACTH), total lymphoid irradiation or bone marrow transplantation at any time ; any cytokine (other than interferon), B cell modulating therapy such as anti-CD 20 antibodies like ocrelizumab or rituximab, or anti-cytokine therapy, plasmapheresis in the last 6 months prior to selection ; ongoing treatment with an experimental drug; preceding treatment with another experimental drug if not washed out for ? 5 halflives or ? 3 months (whichever is longer); - Lymphopenia following treatment with an immunosuppressor or immunomodulator; - Any major medical or psychiatric disorder - History or presence of serious or acute heart disease - Known inability to undergo an MRI scan - positive serology for hepatitis B/C , HIV - abnormal liver function tests (ASAT, ALAT, Total bilirubin >2ULN; AP >3 ULN) - Moderate to Severe Renal impairment - positive pregnancy test - other criteria as stated in the study protocol |
- Pacientes con EMSP o con EMPP; - Cualquier enfermedad distinta de la EM que pudiera explicar mejor los signos y síntomas - Mielitis transversa completa o neuritis óptica bilateral; - Pacientes que hayan sido tratados con: corticoesteroides orales o sistémicos, corticotropina (ACTH) o fingolimod en los 30 días anteriores a la selección; uso de interferón beta o de glatiramero acetato, inmunoglobulina intravenosa (IGIV), natalizumab, dimetilfumarato o teriflunomida en los últimos 3 meses antes de la selección; uso en cualquier momento de mitoxantrona, alemtuzumab, ciclofosfamida, terapia citotóxica o inmunosupresora (excepto corticoesteroides sistémicos y ACTH), irradiación linfoidea total o trasplante de médula ósea, uso de cualquier citocina (distinta del interferón), terapia moduladora de los linfocitos B (p. ej., anticuerpos anti-CD 20, como ocrelizumab o rituximab) o tratamiento anti-citocinas, plasmaféresis, en los últimos 6 meses antes de la selección; tratamiento en curso con un fármaco experimental. En el caso de tratamiento previo con otro fármaco experimental, si no se ha hecho lavado de este durante ? 5 semividas del producto o ? 3 meses (lo que sea más largo); - Linfopenia después del tratamiento con un inmunosupresor o un inmunomodulador; - Cualquier trastorno médico o psiquiátrico de índole mayor - Antecedentes o presencia de cardiopatía grave o aguda, - Incapacidad conocida para la práctica de una RM; - Serología positiva para la hepatitis vírica B y/o C y/o VIH; - Resultados anormales de las pruebas de función hepática (ASAT, ALAT, bilirrubina total > 2 x LSN o fosfatasa alcalina > 3 x LSN); - Insuficiencia renal moderada o severa; - Prueba de embarazo positiva.
- Otros criterios como se indica en el protocolo de estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cumulative number of Gd-enhancing T1 lesions measured using repeated MRI assessments from Week 12 to 24. |
Número acumulado de Di-s-mejora de lesiones T1 medidos usando evaluaciones MRI repetidos desde la semana 12 a 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Week 12 to 24 |
Desde la semana 12 a 24. |
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E.5.2 | Secondary end point(s) |
- Cumulative T2 lesions and CUAL. - Change from baseline (SD1) in T1 and T2 lesion load (T1 and T2 burden of disease) - Relapse (time to first relapse; relapse rate; percentage of patients free of relapse) - Adverse events (AEs) and serious adverse events (SAEs) - Pharmacokinetics (PK) of repeated doses of GNbAC1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-MRI scan: SD1, Week 12, Week 16, Week 20, Week 24, Week 36, Week 48 -Relapse: Week 24 and Week 48 -AEs, SAEs: entire study -PK: on Days 85, 169, 253 and 337 |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, Biomarker 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
France |
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |