E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting multiple sclerosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
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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 this study is to evaluate the dose response relationship among five doses of BAF312 and placebo during 3 months of treatment in patients with RRMS, as measured by the number of combined unique active [MRI] lesions (CUAL). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability (including blood pressure effects) of BAF312 during 6 months and 3 months of treatment in MS patients • To evaluate the dose response relationship of BAF312 and placebo during 6 months of treatment in patients with RRMS, as measured by CUAL • To explore the effect of BAF312 on the number of relapses and thereof derived measures (e.g. annualized relapse rate (ARR), proportion of relapse-free patients) • To explore the correlation of the course of the lymphocyte count with paraclinical (MRI activity) and clinical course
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics/ pharmacogenomics /exploratory biomarkers: These exploratory biomarker sub-studies are optional. These assessments will only be performed on patients who agree to participate by signing the separate exploratory biomarker-blood informed consent. Laboratory manuals will be provided with detailed information on sample collection, handling, and shipment.
Further details are provided in Section 7.6.2 of the protocol. |
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E.3 | Principal inclusion criteria |
1. Patients must give written informed consent before any assessment is performed 2. 18 through 55 years of age inclusive 3. Male or female 4. Females of childbearing potential: • must have a negative pregnancy test at Baseline prior to entry into the double-blind treatment phase • must simultaneously use two forms of effective contraception (either partner) during the treatment and for one months or one menstrual cycle, whichever is longer after discontinuation of the study drug • if either post-menopausal for 12 months prior to randomization or surgically sterile (through hysterectomy or bilateral oophorectomy, if documented), are not required to use birth control (refer to Section 8.3 for more details) 5. Diagnosis of MS as defined by revised McDonald criteria (see Appendix 4) 6. A relapsing-remitting course of disease with • at least 1 documented relapse during the previous year, or • 2 documented relapses during the previous 2 years, or • a positive Gd-enhanced MRI scan at screening (in case the first MRI scan obtained at screening is negative, a second scan may be obtained 1 month later) 7. An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at randomization 8. Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization 9. Patients who decline initiation or continuation of treatment with available disease modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator.
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E.4 | Principal exclusion criteria |
1. A manifestation of another type of MS than RRMS 2. History of chronic disease of the immune system other than MS, or a known immunodeficiency syndrome 3. History or presence of malignancy (except for successfully-treated basal or squamous cell carcinoma of skin) 4. A known, or ‘new’ diagnosis of diabetes mellitus (if screening blood glucose is suspicious for diabetes [≥ 126 mg/dL or ≥ 7 mmol/L if fasting; ≥ 200 mg/dL or 11.1 mmol/L if random testing] a patient should be further evaluated for diabetes mellitus) 5. Diagnosis of macular edema during pre-randomization phase (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic examination at the Screening Visit) 6. Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests, respectively 7. Negative for varicella-zoster virus IgG antibodies at Screening 8. Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to randomization 9. Have received total lymphoid irradiation or bone marrow transplantation 10. Have been treated with: • corticosteroids or ACTH within 1 month prior to randomization • IFN-β or glatiramer acetate within 3 months prior to randomization • immunosuppressive medications such as azathioprine or methotrexate within 6 months prior to randomization • immunoglobulins and/or monoclonal antibodies (including natalizumab) within 6 months prior to randomization (this rule does not apply for alemtuzumab, rituximab, see below) • alemtuzumab, rituximab, cladribine, cyclophosphamide, mitoxantrone, or other immunosuppressive treatments with effects potentially lasting over 6 months, at any time 11. Any medically unstable condition, as assessed by the primary treating physician 12. Any of the cardiovascular conditions listed in the exlusion criteria of the protocol 13. Any of the pulmonary conditions listed in the exclusion criteria of the protocol 14. Any of the hepatic conditions listed in the exlusion criteria of the protocol 15. Any of the abnormal laboratory values listed in the exlusion criteria of the protocol 16. Any of the neurological/psychiatric disorders listed in the exlusion criteria of the protocol 17. Unable to undergo MRI scans due to claustrophobia or metallic implants incompatible with MRI 18. Unable to receive gadolinium-based MRI contrast agents due to a history of hypersensitivity to gadolinium-based contrast agents, or severe renal insufficiency 19. Participation in any clinical research study evaluating another investigational drug or therapy within 3 months prior to randomization 20. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes 21. Homozygosity for CYP2C9*3 (will be tested at Screening), and refusal to test for CYP2C9*3 haplotype 22. Patients using (or having used within four (4) weeks or 5 half- lives, whichever is greater before initial dosing) concomitant medications that are strong or moderate inhibitors or inducers of CYP2C9 (see Appendix 3 for a list of medications that are not allowed during the study). 23. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test (> 5 mIU/mL) 24. History of S1P receptor modulator therapy 25. Any other disease of condition which could interfere with the participation in the study according to the study protocol, or with the ability with the patients to cooperate and comply with the study procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
Monthly number of combined unique active MRI lesions (CUAL) during 3 months of treatment. Combined unique active lesions are defined as new gadolinium [Gd]-enhancing lesions on T1-weighted MRI scans or new or enlarging lesions on T2-weighted MRI scans, without double-counting of lesions.
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
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 |
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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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |