E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
relapsing-remitting multiple sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
relapsing-remitting multiple sclerosis |
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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 | 17.0 |
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 |
To determine if a monoclonal antibody VAY736 can reduce disease activity in relapsing-remitting multiple sclerosis (RRMS) as compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of VAY736 in patients with RRMS.
To evaluate the effect of VAY736 on additional parameters observed on brain MRI scans including:
- Number of all T1-weighted Gd-enhancing lesions
- Number of new or enlarging T2-weighted lesions
- T2 burden of disease (total volume of T2-weighted lesions)
- Proportion of subjects without any new MRI disease activity (no new Gd-enhancing lesions nor new or enlarging T2 lesions)
To evaluate the effect of VAY736 on the number of relapses
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male and female patients 18 to 55 years of age.
-Diagnosis of MS as defined by the 2010 revised McDonald criteria (Polman, et. al. 2011).
-A relapsing-remitting course of disease with:
at least 1 documented relapse during the previous 12 months (but not within 30 days prior to randomization as per criterion 6), or a positive Gd-enhancing lesion on brain MRI scan at screening.
-An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at screening.
-No evidence of a relapse within 30 days prior to randomization.
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E.4 | Principal exclusion criteria |
-A manifestation of another type of MS other than RRMS.
-Findings on screening or baseline brain MRI inconsistent with the diagnosis of MS.
-History of chronic disease of the immune system other than MS, or a known immunodeficiency syndrome.
-Unable to undergo MRI scans due to inter-alia, claustrophobia, incompatible cardiac pacemakers, ferromagnetic intracranial, Aneurysm clips, certain cochlear implants, and certain other ferromagnetic foreign bodies (e.g. tattoos containing metal) or electronic devices, or metallic implants incompatible with MRI.
-Unable to receive gadolinium-based MRI contrast agents due to a history of hypersensitivity to gadolinium-based contrast agents, renal insufficiency or impairment.
-Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the course of the study and for 4 months following completion of the study.
-Have received total lymphoid irradiation, bone marrow transplantation, alemtuzumab, cladribine, cyclophosphamide, mitoxantrone, or other immunosuppressive treatments with effects lasting longer than 6 months (wash-out times for other registered or putative immunomodulators or immunosupressants apply)
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E.5 End points |
E.5.1 | Primary end point(s) |
Cumulative number of new Gd-enhancing lesions. |
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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) |
-Number of new and cumulative number of new T1-weighted Gd-enhancing lesions.
-Number of all T1-weighted Gd-enhancing lesions.
-Cumulative number of new or enlarging T2-weighted Gd-enhancing lesions.
-T2 burden of disease
-Proportion of subjects without any new MRI disease activity.
-The number of confirmed relapses at week 16
-Proportion of relapse-free patients over the 16 weeks of the treatment period
-Number of patients with adverse events |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | 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 | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Partially blind (Investigators and patients will be unblinded to treatment assignment after week 16) |
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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 | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Russian Federation |
Ukraine |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |