E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Remitting-Relapsing Multiple Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
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. |
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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. |
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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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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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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants relapse-free at Month 6 in RRMS participants |
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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 |
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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. |
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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. |
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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.8.5 | 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 | 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 |
Canada |
Denmark |
France |
Germany |
Italy |
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
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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 | 1 |
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 |