E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Remitting-Relapsing Multiple Sclerosis |
sclerosi multipla recidivante remittente |
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E.1.1.1 | Medical condition in easily understood language |
Multiple Sclerosis |
Sclerosi multipla |
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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 | 21.1 |
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 evaluate the effects of treatment with daclizumab on the proportion of participants relapse-free at 6 months in Relapsing-Remitting Multiple Sclerosis (RRMS) participants, who switched from treatment with natalizumab to daclizumab due to safety concerns. |
L¿obiettivo primario dello studio consiste nel valutare gli effetti del trattamento con daclizumab sulla percentuale di partecipanti che non mostrano recidive a 6 mesi tra i partecipanti affetti da sclerosi multipla recidivante remittente (SMRR), che sono passati dal trattamento con natalizumab a daclizumab permotivi di sicurezza. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study in this study population are to evaluate the effects of daclizumab on the following: 1) Multiple Sclerosis (MS) relapse activity including the annualized relapse rate (ARR) and the proportion of participants experiencing relapses requiring hospitalization and/or steroid treatment; 2) MS-related outcomes measured using magnetic resonance imaging (MRI); 3) Safety and tolerability in participants previously treated with natalizumab. |
Gli obiettivi secondari di questo studio in questa popolazione di studio consistono nel valutare gli effetti di daclizumab su quanto segue: 1) attivit¿ della recidiva di sclerosi multipla (SM), compresi il tasso annualizzato di recidiva (ARR) e la percentuale di partecipanti che manifestano recidive e necessitano di ricovero e/o trattamento steroideo; 2) esiti correlati alla SM misurati mediante risonanza magnetica (RMI); 3) sicurezza e tollerabilit¿ in partecipanti precedentemente trattati con natalizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria
1. Must have documented diagnosis of RRMS (McDonald 2010 Criteria) at screening [Polman 2011].
2. Must have been treated with natalizumab for at least the 12 months prior to screening and have not missed 2 or more consecutive scheduled doses.
3. Must be naïve to daclizumab and other forms of daclizumab such as Zenapax® prior to enrollment.
4. Must have a confirmed Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive, at screening.
5. Female participants of childbearing potential must practice effective contraception from Day -1 and be willing and able to continue contraception for duration of the study.
NOTE: Other protocol defined Inclusion criteria may apply.
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1. I soggetti devono presentare una diagnosi documentata di SMRR (Criteri McDonald 2010) allo screening [Polman 2011]. 2. I soggetti devono essere stati trattati con natalizumab per almeno i 12 mesi precedenti lo screening e non devono aver saltato 2 o più dosi consecutive programmate. 3. I soggetti devono essere naïve a daclizumab e altre forme di daclizumab quali Zenapax® prima dell’arruolamento. 4. I soggetti devono avere un punteggio confermato sulla Scala di invalidità espansa (EDSS) compreso tra 0 e 5,5 (estremi compresi) allo screening. 5. Le partecipanti in età fertile devono adottare metodi contraccettivi efficaci a partire dal Giorno -1 e devono essere disposte e in grado di continuare la contraccezione per tutta la durata dello studio. NOTA: possono essere applicati altri criteri di inclusione definiti dal protocollo. |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria
1. Current participation in another investigational study.
2. Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold) [Lublin 2014].
3. Females breastfeeding, pregnant, or planning to become pregnant; or women who have a positive pregnancy test result during screening.
4. History of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to screening.
5. History of severe opportunistic infections (including progressive multifocal leukoencephalopathy (PML)) or any clinically significant, cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator.
6. Discontinued natalizumab due to suspicion of PML.
7. Known active malignancies (participants with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible).
8. The participant is using another MS therapy concomitantly.
9. Known history of human immunodeficiency virus (HIV).
10. Positive test result for Hepatitis C virus (test for hepatitis C virus antibody [HCV Ab]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).
11. The participant has been treated with immunosuppressive or immunomodulating treatments including mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate mofetil.
NOTE: Other protocol defined Exclusion criteria may apply.
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1. Attuale partecipazione a un altro studio sperimentale. 2. Diagnosi di SM primaria progressiva, secondaria progressiva o progressiva recidivante (definita secondo Lublin e Reingold) [Lublin 2014]. 3. Soggetti di sesso femminile in allattamento, in gravidanza o che prevedano di iniziare una gravidanza; o donne che risultano positive al test di gravidanza durante lo screening. 4. Anamnesi di abuso di alcol o sostanze stupefacenti (in base al giudizio dello Sperimentatore) nell’anno precedente lo screening. 5. Anamnesi di infezioni opportunistiche gravi (compresa leucoencefalopatia multifocale progressiva [PML]) o qualsiasi malattia cardiaca, endocrinologica, ematologica, epatica, immunologica, metabolica, urologica, polmonare, neurologica (diversa da SM), dermatologica, psichiatrica e renale clinicamente significativa o qualsiasi altra grave malattia determinata dallo sperimentatore. 6. Interruzione di natalizumab per sospetto di PML. 7. Neoplasie maligne attive note (i partecipanti con carcinoma cutaneo basocellulare che è stato completamente escisso prima dello studio rimangono idonei). 8. Il partecipante sta facendo uso di un’altra terapia concomitante per la SM. 9. Anamnesi nota di infezione da virus dell’immunodeficienza umana (HIV). 10. Risultato positivo al test per il virus dell’epatite C (test per l’anticorpo anti-virus dell’epatite C [HCV Ab] o virus dell’epatite B (test per l’antigene di superficie dell’epatite B [HBsAg] e/o anticorpo anti-core del virus dell’epatite B [HBcAb]). 11. Il partecipante è stato trattato con terapie immunosoppressive o immunomodulanti compresi mitoxantrone, azatioprina, metotrexato, ciclofosfamide o micofenolato mofetile. NOTA: possono essere applicati altri criteri di esclusione definiti dal protocollo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants relapse-free at Month 6 in RRMS participants |
Percentuale di partecipanti senza recidive al Mese 6 tra i partecipanti con SMRR |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Proportion of participants relapse-free at Month 6 in RRMS participants |
Percentuale di partecipanti senza recidive al Mese 6 tra i partecipanti con SMRR |
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E.5.2 | Secondary end point(s) |
Proportion of participants relapse-free at Month 12. Proportion of participants experiencing relapse requiring hospitalization and/or steroid treatment at Month 12. Annualized relapse rate (ARR) at Month 12. Number of new gadolinium (Gd+) enhanced and T1 hypointense lesions at Month 6 on MRI. Number of new Gd+ enhanced and T1 hypointense lesions at Month 12 on MRI. Number of new or newly enlarged T2 hyperintense lesions at Month 6 on MRI. Number of new or newly enlarged T2 hyperintense lesions at Month 12 on MRI. Permanent discontinuation rate of daclizumab at Month 12. Number of participants that experience Adverse Events (AEs) or Serious Adverse Events (SAEs). Number of participants with clinical relevant shifts in laboratory assessments. |
Percentuale di partecipanti senza recidive al Mese 12.
Percentuale di partecipanti che manifestano recidive e necessitano di ricovero e/o trattamento steroideo al Mese 12.
Tasso annualizzato di recidiva (ARR) al Mese 12.
Numero di nuove lesioni captanti il gadolinio (Gd+) e ipointense in T1 alla RMI al Mese 6.
Numero di nuove lesioni captanti Gd+ e ipointense in T1 alla RMI al Mese 12.
Numero di lesioni, nuove o di recente espansione, iperintense in T2 alla RMI al Mese 6.
Numero di lesioni, nuove o di recente espansione, iperintense in T2 alla RMI al Mese 12
Tasso di interruzione permanente di daclizumab al Mese 12.
Numero di partecipanti che manifestano eventi avversi (EA) o eventi avversi gravi (SAE).
Numero di partecipanti con variazioni clinicamente rilevanti nelle valutazioni di laboratorio.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Proportion of participants relapse-free at Month 12. Proportion of participants experiencing relapse requiring hospitalization and/or steroid treatment at Month 12. Annualized relapse rate (ARR) at Month 12. Number of new gadolinium (Gd+) enhanced and T1 hypointense lesions at Month 6 on MRI. Number of new Gd+ enhanced and T1 hypointense lesions at Month 12 on MRI. Number of new or newly enlarged T2 hyperintense lesions at Month 6 on MRI. Number of new or newly enlarged T2 hyperintense lesions at Month 12 on MRI. Permanent discontinuation rate of daclizumab at Month 12. Number of participants that experience Adverse Events (AEs) or Serious Adverse Events (SAEs) up to 15 months. Number of participants with clinical relevant shifts in laboratory assessmentsup to 15 months. |
Percentuale di partecipanti senza recidive al Mese 12. Percentuale di partecipanti che manifestano recidive e necessitano di ricovero e/o trattamento steroideo al Mese 12. Tasso annualizzato di recidiva (ARR) al Mese 12. Numero di nuove lesioni captanti il gadolinio (Gd+) e ipointense in T1 alla RM al Mese 6. Numero di nuove lesioni captanti Gd+ e ipointense in T1 alla RMI al Mese 12. Numero di lesioni, nuove o di recente espansione, iperintense in T2 alla RMI al Mese 6. Numero di lesioni, nuove o di recente espansione, iperintense in T2 alla RMI al Mese 12. Tasso di interruzione permanente di daclizumab al Mese 12. Numero di partecipanti che manifestano eventi avversi (EA) o eventi avversi gravi (SAE) fino a 15 mesi. Numero di partecipanti con variazioni clinicamente rilevanti nelle valut |
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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.8.3 |
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 | 30 |
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 | Information not present in EudraCT |
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 |
Canada |
United States |
Denmark |
France |
Germany |
Italy |
United Kingdom |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |