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 |
multiple sclerosis with relapses |
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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 |
To assess the long-term safety and tolerability of AIN457 over a period of up to 1 year in patients with relapsing-remitting multiple sclerosis who particpated in the core CAIN457B2201 Phase II proof of concept (PoC) study
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term efficacy on clinical grounds (annualized relapse rate, disability progression) and by means of of imaging methods (neuroradiological measures of neurodegeneration and neuroinflammation) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Was exposed to AIN457 or placebo in study CAIN457B2201 study, up to at and including Visit 10 (Week 24)
Other protocol defined inclusion/exclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1. Have been treated with:
• immunosuppressive medications such as azathioprine or methotrexate within 1 month prior to enrollment, if lymphocyte count normal.
• immunoglobulins and/or monoclonal antibodies (with the exception of AIN457) within 2 month prior to enrollment, or if the immunosuppressive effects are likely to persist at enrollment (such as presence of B cell depletion after rituximab treatment).
2. Have received total lymphoid irradiation, bone marrow transplantation, alemtuzumab, cladribine, cyclophosphamide, mitoxantrone or other immunosuppressive treatments with long-lasting (over 6 months) or permanent effects.
3. Have received any live or live attenuated vaccines (including live vaccines for varicella-zoster virus or measles) within 2 months prior to enrollment.
4. A diagnosis of chronic disease of the immune system other than MS, or of an immunodeficiency syndrome.
5. Current severe depression.
6. Pregnant or nursing (lactating) women.
7. Malignancy diagnosed since enrollment in the core study (except for successfully-treated basal or squamous cell carcinoma of skin).
8. A new diagnosis of diabetes
9. Positive testing for tuberculosis (QuantiFeron or chest X-ray).
10. Subjects with clinically significant cardiac abnormalities
11. Unable or unwilling to undergo multiple venipunctures
12. Unable to undergo MRI scans due to newly acquired claustrophobia or metallic implants incompatible with MRI.
Other protocol-defined inclusion/exclusion criteria may apply
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability of AIN457
The primary variables are related to the following safety assessments: ECGs, vital signs, and AEs. Where AEs are related to infections they will be analyzed separately. Summary statistics and listing will be provided for these endpoints.
In addition physical examinations and standard clinical laboratory evaluations will be done. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ECG at screening, at first administration, end of treatment and study completion
AE and vital signs at every visit
Vital signs at every visit up to 12 months of treatment and then every 3 months during the whole treatment period duration, at end of treatment and study completion
Laboratory evaluations at screening, baseline, at first administration, at 6 months of treatment, at 12 months of treatment and every 3 months during the whole treatment period duration, at end of treatment and study completion.
Physical examination at screening, baseline, at first administration, at 6 months of treatment, at 12 months of treatment and every 6 months during the whole treatment period duration, at end of treatment and study completion.
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E.5.2 | Secondary end point(s) |
Long term efficacy of AIN457
Assessment by
annualized relapse rate (ARR)
disability progression via EDSS
neuroradiological measures of neurodegeneration via brain volume (MRI), neuroradiological measures of neuroinflammation via absolute number of gadolinium (Gd)-enhanced lesions on T1-weighted scans, new or enlarging lesions on T2 weighted lesions (MRI) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ARR at every visit
EDSS at baseline, at 6 months of treatment, at 17 months of treatment and then every year during the duration of the treatment period, at end of treatment and study completion.
MRI at treatment start, at 3, 6 and 9 months of treatment, at 17 months of treatment and then every year during the duration of the treatment period, at end of treatment and study completion.
Comparison of key secondary variables (ARR, EDSS and MRI endpoints) with historic information from prior studies in MS including the core (CAIN457B2201) study will be done
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | No |
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 |
Czech Republic |
Russian Federation |
Ukraine |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |