Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod (BAF312) in Patients With Secondary Progressive Multiple Sclerosis Followed by Extended Treatment With Open-label BAF312.
Brief Summary: Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment duration in patients with secondary progressive multiple sclerosis (Core Part) followed by extended treatment with open-label BAF312 to obtain data on long-term safety, tolerability and efficacy (Extension Part).


Options:
A: Inclusion Criteria:

* Prior history of relapsing remitting MS
* SPMS defined as progressive increase of disability over at least 6 months
* EDSS score of 3.0 to 6.5
* No relapse of corticosteroid treatment within 3 months

Exclusion Criteria:

* Women of child bearing potential must use reliable forms of contraception.
* Diagnosis of Macular edema during screening period
* Any medically unstable condition determined by investigator.
* Unable to undergo MRI scans
* Hypersensitivity to any study drugs or drugs of similar class
B: Core Study

Inclusion Criteria:

* Diagnosis of relapsing multiple Sclerosis (MS)
* Patients with at least two documented relapses in the previous 2 years or one documented relapse in the last year
* Patients with an Expanded Disability Status Scale (EDSS) score of 0-6

Extension Study

* A positive Gd-enhanced MRI scan at screening (in case the first MRI scan obtained at screening was negative, a second scan could have been obtained 1 month later)
* Neurologically stable with no evidence of relapse within 30 days prior to randomization,or during the Screening and Baseline periods.
* Female patients either post-menopausal, surgically incapable of bearing children, or practicing an acceptable method of birth control. Females of childbearing potential with a negative pregnancy test at baseline prior to entry into the treatment period.

Exclusion Criteria:

Core Study

* Patients with other chronic disease of the immune system, malignancies, pulmonary or heart disease, etc
* Pregnant or nursing women

Extension Study

* Patients who had permanently discontinued study drug prior to the Month 6 visit of the core study
* Patients with diabetes mellitus (to reduce the risk of ME), and therefore ongoing patients with diabetes mellitus or who developed diabetes mellitus were discontinued from the study)

Other protocol-defined inclusion/exclusion criteria may apply
C: Part A

Key Inclusion Criteria:

* Must give written informed consent and any authorizations required by local law.
* Must have a diagnosis of relapsing-remitting MS, as defined by the revised McDonald criteria 1 through 4 (Polman et al, 2005). All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the Investigator.
* Japanese men and women aged 18 to 65, inclusive, at the time of informed consent.
* All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be able to continue contraception for 12 weeks after their last dose of study treatment.
* Must have an Expanded Disability Status Scale (EDSS) score between 0.0 and 6.0, inclusive.
* Must have experienced at least 1 medically documented clinical exacerbation within 12 months of enrollment.
* Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including interferon beta \[IFNβ\] and chronic systemic corticosteroids) for the duration of the study.
* Must have a baseline MRI, conducted within 35 calendar days prior to enrollment.

Key Exclusion Criteria:

* Diagnosis or history of neuromyelitis optica (NMO), e.g., a long spinal lesion extending over 3 or more vertebral bodies was detected, or the subject has a history of positive tests for anti-aquaporin-4 (anti-AQP4) antibodies.
* The subject is considered by the Investigator to be immunocompromised, based on medical history, physical examination, laboratory testing, or prior immunosuppressive or immunomodulating treatment.
* An MS exacerbation (relapse) within 30 days prior to enrollment or, in the opinion of the Investigator, the subject has not stabilized from a relapse prior to enrollment at Week 0.
* History of malignancy.
* Known history of, or positive test result for human immunodeficiency virus (HIV) infection.
* Known history of or positive test result for hepatitis C virus or hepatitis B virus within the year prior to enrollment.
* History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
* A clinically significant infectious illness within 30 days prior to enrollment.
* Abnormal liver function test results at screening: alanine aminotransferase (ALT), or aspartate aminotransferase (AST) \>2 times of the upper limit of normal (ULN) or bilirubin \>1.5 times of the ULN during screening.
* Previous treatment with natalizumab, any murine protein, or any other therapeutic monoclonal antibody.
* Any prior treatment with any of the following medications: total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination.
* Treatment with immunosuppressant medications, e.g., azathioprine, cyclophosphamide, methotrexate, and fingolimod within 6 months prior to enrollment, or mitoxantrone and cyclosporine within 12 months prior to enrollment.
* Treatment with any of the following medications or procedures within 6 months prior to enrollment: intravenous immunoglobulin (IVIg), plasmapheresis, or cytapheresis.
* Treatment with immunomodulatory medications (including IFNβ and glatiramer acetate \[GA\]) within 2 weeks of enrollment.
* Treatment with any of the following medications within 30 days of enrollment: intravenous corticosteroid treatment, systemic corticosteroid treatment, 4-aminopyridine or related products.
* Participation in any other investigational treatment within the 6 months prior to enrollment or concurrent with this study.

Part B

Key Inclusion Criteria:

* Must give written informed consent and any authorizations required by local law.
* Must have a diagnosis of relapsing-remitting MS, as defined by the revised McDonald criteria 1 through 4 (Polman et al, 2005). All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the Investigator.
* Japanese men and women aged 18 to 65, inclusive, at the time of informed consent.
* All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be able to continue contraception for 12 weeks after their last dose of study treatment.
* Must have an EDSS score between 0.0 and 5.5, inclusive.
* Must have experienced at least 1 medically documented clinical exacerbation within 12 months of enrollment.
* Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFNβ and chronic systemic corticosteroids) for the duration of the study.
* Prior to enrollment all subjects must have: a screening MRI, or documentation of an MRI within the subject's medical record within 1 year of the screening visit, which reveals 3 or more T2 hyperintense lesions consistent with MS, and a baseline MRI, conducted within 7 calendar days prior to enrollment, which reveals at least 1 MRI lesion consistent with MS.

Key Exclusion Criteria

* Diagnosis or history of NMO, e.g., a long spinal lesion extending over 3 or more vertebral bodies was detected, or the subject has a history of positive tests for anti-AQP4 antibodies.
* The subject is considered by the Investigator to be immunocompromised, based on medical history, physical examination, laboratory testing, or prior immunosuppressive or immunomodulating treatment.
* An MS exacerbation (relapse) within 30 days prior to enrollment or, in the opinion of the Investigator, the subject has not stabilized from a relapse prior to enrollment at Week 0.
* History of malignancy.
* Known history, or positive test result of HIV infection.
* Known history of or positive test result for hepatitis C virus or hepatitis B virus within the year prior to Enrollment.
* History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
* A clinically significant infectious illness within 30 days prior to Enrollment.
* Abnormal liver function test results at screening: ALT or AST \>2 times of the ULN or bilirubin \>1.5 times of the ULN during screening.
* Previous treatment with natalizumab, any murine protein, or any other therapeutic monoclonal antibody.
* Any prior treatment with any of the following medications: total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination.
* Treatment with immunosuppressant medications, e.g., azathioprine, cyclophosphamide, methotrexate, and fingolimod within 6 months prior to enrollment, or mitoxantrone and cyclosporine within 12 months prior to enrollment.
* Treatment with any of the following medications or procedures within 6 months prior to enrollment: IVIg, plasmapheresis, or cytapheresis.
* Treatment with immunomodulatory medications (including IFNβ and GA) within 2 weeks of enrollment.
* Treatment with any of the following medications within 30 days of enrollment: intravenous corticosteroid treatment, systemic corticosteroid treatment, 4-aminopyridine or related products.
* Participation in any other investigational treatment within the 6 months prior to enrollment or concurrent with this study.

NOTE: Other protocol defined inclusion/exclusion criteria may apply.
D: Key Inclusion Criteria (Part 1):

* Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations.
* SPMS defined as relapsing-remitting disease followed by progression of disability independent of or not explained by multiple sclerosis (MS) relapses for at least 2 years.
* EDSS score of 3.0 to 6.5, inclusive.
* Multiple Sclerosis Severity Score of 4 or higher.
* Documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to enrollment as defined in the Study Reference Guide.

Key Exclusion Criteria (Part 1):

* Relapsing remitting multiple sclerosis (RRMS) or primary progressive MS as defined by the revised McDonald Committee criteria.
* Clinical relapse (within 3 months) prior to randomization.
* T25FW test of \>30 seconds during the screening period.
* Any value below the lower limit of normal for blood levels of leukocytes, lymphocytes, or neutrophils.
* Considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment.
* Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed).
* History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study.
* History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
* Known history of or positive test result for human immunodeficiency virus.
* Positive test result for hepatitis C virus (test for hepatitis C virus antibody or hepatitis B virus (test for hepatitis B surface antigen and/or hepatitis B core antibody).
* History of transplantation or any anti-rejection therapy.
* Presence of any infectious disease (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening.
* History of progressive multifocal leukoencephalopathy or other opportunistic infections.

Treatment History (Part 1)

* Any prior treatment with cell-depleting therapies, including total lymphoid irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation.
* Any prior treatment with natalizumab.
* Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization.
* Treatment with intravenous or oral corticosteroids, intravenous immunoglobulin, or plasmapheresis for treatment of MS within the 3 months prior to randomization.
* Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks prior to randomization.
* Treatment with 4-aminopyridine within 30 days prior to randomization, unless a stable dose has been maintained for at least 30 days prior to randomization and will be continued for the course of this study.

Key Inclusion Criteria (Part 2):

* Subjects must have participated in and completed Part 1 per protocol, and have documented assessment attempts for EDSS, T25FW, and 9HPT prior to first open-label dosing.

Key Exclusion Criteria (Part 2):

* Subjects with any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in this extension study. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment.
* Subjects who discontinued study treatment in Part 1 OR had fewer than 20 infusions in Part 1 OR missed 2 or more consecutive infusions in Part 1.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Answer: A