E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing Remitting Multiple Sclerosis (RRMS) |
Sclerosi Multipla Recidivante Remittente (SMRR) |
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E.1.1.1 | Medical condition in easily understood language |
Autoimmune disease of the central nervous system characterized by alternating relapses. |
Malattia autoimmune del Sistema Nervoso centrale caratterizzata da alternanza di ricadute |
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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 | 14.1 |
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 of the study is to assess the BG00012 treatment effect on cognition over 2 year period in RRMS patients |
L’obiettivo primario dello studio consiste nel valutare l’effetto del trattamento con BG00012 sulle funzioni cognitive nei pazienti affetti da SMRR in un periodo di 2 anni |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to further assess BG-12 treatment effect on cognition, predictors of cognitive impairment, clinical efficacy, and patient reported outcomes. In additional the relationship between cognition and patient reported outcome on depression, fatigue, quality of life, and work and social life activity will be examined.
Additional Assessment:
- any adverse event (including relapses) that could occur throughout the study
- comparison of Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) versus Rao’s Brief Repeatable Battery of Neuropsychological Tests (BRB) together with Stroop Test as a screening tool of cognitive impairment in patients with RRMS. |
L’obiettivo secondario dello studio è di valutare ulteriormente l’effetto del trattamento con BG00012 sulle funzioni cognitive, sui fattori predittivi del deficit cognitivo, sull’efficacia clinica e sui “patient reported outcomes”. Sarà inoltre esaminata la relazione tra funzioni cognitive e “patient reported oucomes” su depressione, “fatigue, qualità della vita e attività lavorativa e sociale.
Ulteriori valutazioni:
- qualsiasi evento avverso (incluse le recidive) che si verifichi durante lo studio
- confronto della performance della batteria di Rao e Stroop Test e della batteria BICAMS nella valutazione delle funzioni cognitive
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with local subject privacy regulations.
2. Age ≥18 years at the time of informed consent.
3. Must have a confirmed diagnosis of RRMS according to McDonald criteria (Polman, Reingold et al. 2005).
4. Must have a baseline EDSS between 0.0 and 5.0, inclusive.
5. Must have experienced at least 1 relapse within the 12 months prior to randomization, with a prior brain MRI demonstrating lesion(s) consistent with MS, or show evidence of Gd-enhancing lesion(s) of the brain on an MRI performed within the 6 weeks prior to randomization.
6. Subjects of childbearing potential (including female subjects who are not post-menopausal for at least 1 year) must practice effective contraception (as defined by the Investigator) during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment. For further details of contraceptive requirements for this study, please refer to Section 15.5.3. |
1. Capacità di comprendere lo scopo e rischi dello studio e fornire firmato e datato il consenso informato firmato e datato e l'autorizzazione ad utilizzare le informazioni sanitarie personali, in conformità con la normativa sulla privacy locale.
2. età ≥ 18 anni al momento del consenso informato
3. Deve avere una diagnosi confermata di SMRR in base a criteri di McDonald (Polman, Reingold et al. 2005)
4. Deve avere un EDSS al basale compreso tra 0.0 e 5.0, incluso
5. Deve aver sperimentato almeno 1 recidiva nei 12 mesi precedenti la randomizzazione, con una lesione al cervello rilevata da MRI compatibile con MS, o che mostri segni di lesione del cervello captante il gadolinio da MRI effettuata entro 6 settimane prima della randomizzazione.
6. Soggetti in età fertile (inclusi soggetti di sesso femminile che non sono in post-menopausa da almeno 1 anno) devono adottare un sistema di contraccezione efficace (come definito dallo sperimentatore) durante lo studio ed essere disposti e in grado di continuare la contraccezione per 30 giorni dopo la loro ultima dose di trattamento di studio. Per ulteriori dettagli su requisiti di contraccettivi per questo studio, si prega di fare riferimento alla Sezione 15.5.3 del protocollo. |
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E.4 | Principal exclusion criteria |
1. Primary progressive, secondary progressive, or progressive relapsing MS, as defined by Lublin and Reingold (Lublin and Reingold 1996)
2. Severe depression (MADRS score >34) (Montgomery and Asberg 1979)
3. History of malignancy (except basal cell carcinoma that has been completely excised prior to study enrollment)
4. History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
For a complete list see te protocol |
1. Sclerosi multipla progressiva primaria, secondaria progressiva o progressiva recidivante come definito da Lublin and Reingold (Lublin and Reingold 1996)
2. Depressione grave (MADRS score >34) (Montgomery and Asberg 1979)
3. Storia di neoplasia maligna (eccetto il carcinoma a cellule basali, che è stato completamente asportato prima dell'arruolamento nello studio)
4. Storia di gravi reazioni allergiche o anafilattiche o ipersensibilità conosciuta ai farmaci.
Per un elenco completo dei criteri di esclusione si faccia riferimento al protocollo
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with worsening in CI. |
Proporzione di pazienti con un peggioramento del peggioramento cognitivo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Change in cognitive impairment index score (CII) over two years
•Annualized relapse rate (ARR) at year 1 and year 2. Proportion of relapse at year 1 and year 2, and time to relapse over 2 years.
•Proportion of patients with 6-month sustained progression of disability
• Assessment of baseline demographic, disease characteristics and related patient reported outcomes that predict CI at two years.
•Change from baseline over two years in patient reported outcomes:
- Depression
- Fatigue- Quality of life- Work/social life activity |
• Variazioni del Cognitive Impairment Index score (CII) a 2 anni.
• Tasso annualizzato di ricadute (Annualized relapse rate, ARR) a 1 e 2 anni. Proporzione di pazienti con ricadute a 1 e 2 anni e tempo alla recidiva a 2 anni.
• Proporzione di pazienti con progressione di disabilità mantenuta a 6 mesi
• Valutazione al basale dei dati demografici, delle caratteristiche della malattia e dei “patient reported outocomes” predittivi di un CI a 2 anni.
• Variazione dal basale a 2 anni nei seguenti “patient reported outcomes”:
- Depressione
- “Fatigue”
- Qualità della vita
- Attività lavorativa/vita sociale
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 24 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |