Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Design Study to Evaluate the Efficacy and Safety of Teriflunomide in Reducing the Frequency of Relapses and Delaying the Accumulation of Physical Disability in Subjects With Multiple Sclerosis With Relapses
Brief Summary: The primary objective was to determine the effect of teriflunomide on the frequency of relapses in patients with relapsing multiple sclerosis (MS).

Secondary objectives were:

* to evaluate the effect of teriflunomide on the accumulation of disability as measured by Expanded Disability Status Scale \[EDSS\], the burden of disease as measured by Magnetic Resonance Imaging \[MRI\] and patient-reported fatigue;
* to evaluate the safety and tolerability of teriflunomide.


Options:
A: Inclusion Criteria:

* Willing and able to sign written Informed Consent;
* Female and male subjects aged 18-55 years inclusive at the time of Informed Consent signing;
* Diagnosis of RRMS according to the revised McDonald criteria;
* Expanded Disability Status Scale (EDSS) score of 0.0 up to and including 5.5;
* Neurologically stable with no evidence of relapse within 30 days prior to randomization;
* Experienced at least 1 relapse in the year before first screening assessment;
* At least 1 T1-weighted Gadolinium enhancing (T1-GdE) lesion on routine brain MRI taken within 3 months of starting screening or on screening brain MRI (as confirmed by central imaging laboratory;
* Having a routine brain MRI showing maximally 15 T1-GdE lesions if scan is taken without subject receiving immuno-modulatory treatment, or a routine brain MRI showing maximally 5 T1-GdE lesions when taken while on immuno-modulatory treatment, or a screening MRI showing maximally 15 T1-GdE lesions;
* Must decline initiation or continuation of treatment with other available disease-modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator;
* Female subjects of childbearing potential must agree to practice appropriate contraceptive methods as assessed by the investigator.

Exclusion Criteria:

* Any life-threatening, medically unstable or otherwise clinically significant condition or findings other than MS, in particular neoplastic disease, seizure disorders, or psychiatric disease;
* Any clinically significant deviation from reference ranges in laboratory tests;
* Positive laboratory test results for human immunodeficiency virus (HIV), HBsAg or HCV at screening;
* Any significant deviation from reference ranges for hepatic function;
* Positive urine drug screen or history of substance abuse within the year before screening (any use of illicit or prescription drugs or alcohol constituting an abuse pattern in the opinion of the investigator);
* Having been treated with or having received

  1. at any time:

     * glatiramer acetate, cladribine, rituximab, cyclophosphamide, alemtuzumab, or other immunosuppressive treatments with effects potentially lasting for more than 6 months
     * total lymphoid irradiation or bone marrow transplantation
  2. within one year before screening:

     * mitoxantrone, but subject cannot be enrolled when mitoxantrone was taken at a cumulative lifetime dosing above 100 mg/m2
  3. within 6 months before screening:

     * fingolimod, immunoglobulins and/or monoclonal antibodies (including natalizumab), leflunomide, or putative MS treatments
     * chronic oral or injected corticosteroids or injected ACTH (more than 30 consecutive days)
  4. within 3 months before screening:

     * azathioprine, methotrexate
     * plasma exchange
     * any other experimental intervention, in particular experimental drugs
  5. within 1 month before screening:

     * Interferon-β 1a or 1b
     * short-term oral or injectable corticosteroids for treatment of a relapse
     * short-term ACTH
* Having, in the opinion of the investigator, consecutively failed on efficacy grounds two full and adequate courses of accepted treatment modalities (normally at least one year of treatment for each);
* Pregnancy or breastfeeding;
* Known hypersensitivity to gadolinium-containing products, glatiramer acetate or mannitol;
* Having an estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73m2;
* Inability to undergo (repeat) MRI investigations as judged by the investigator, e.g. due to claustrophobia, metal implants or fragments, tattoos or permanent make-up;
* Any reason why, in the investigator's opinion, the subject should not participate.
B: Inclusion Criteria:

Male and female subjects aged 18 to 55 years with established diagnosis of MS McDonald 2010 with relapsing course from onset (i.e., RRMS and SPMS with superimposed relapses).

Subjects must have active disease evidenced by one or more MS attacks with onset within the period of 12 to 1 months prior to randomization, or by two or more MS attacks with onset within the 24 to 1 months prior to randomization, or with one or more gadolinium-enhancing (Gd+) lesion(s) of the brain on an MRI performed within 6 months prior to randomization.

Enrolled subjects must be ambulatory (EDSS score of up to 5.5 inclusive) and may be treatment-naïve or previously treated with MS disease modifying therapy.

Exclusion Criteria:

Subjects with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic,ophthalmological conditions) or lactating or pregnant women are not eligible to enter the study.

Subjects with contraindications to MRI or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study are not eligible to enter the study.
C: Inclusion Criteria:

* Diagnosis of multiple sclerosis, in accordance with the revised McDonald criteria (2010)
* At least 2 documented clinical attacks within the last 2 years prior to screening or one clinical attack in the years prior to screening (but not within 30 days prior to screening)
* Neurologic stability for greater than or equal to (\>/=) 30 days prior to both screening and baseline
* Expanded Disability Status Scale (EDSS) score 0 to 5.5 inclusive

Exclusion Criteria:

* Primary progressive multiple sclerosis
* Disease duration of more than 10 years in patients with EDSS score less than or equal to (\</=) 2.0 at screening
* Contraindications for MRI
* Known presence of other neurological disorders which may mimic multiple sclerosis
* Pregnancy or lactation
* Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History of or currently active primary or secondary immunodeficiency
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
* Active infection, or history of or known presence of recurrent or chronic infection (for example, hepatitis B or C, Human Immunodeficiency Virus \[HIV\], syphilis, tuberculosis)
* History of progressive multifocal leukoencephalopathy
* Contraindications to or intolerance of oral or IV corticosteroids
* Contraindications to Rebif or incompatibility with Rebif use
D: Inclusion Criteria:

* Multiple sclerosis \[MS\] subject who was ambulatory (EDSS of ≤ 5.5)
* Exhibiting a relapsing clinical course, with or without progression (relapsing remitting, secondary progressive or progressive relapsing);
* Meeting McDonald's criteria for MS diagnosis;
* Experienced at least 1 relapse over the 1 year preceding the trial or at least 2 relapses over the 2 years preceding the trial;
* No relapse onset in the preceding 60 days prior to randomization;
* Clinically stable during the 30 days prior to randomization, without adrenocorticotrophic hormone \[ACTH\] or systemic steroid treatment.

Exclusion Criteria:

* Clinically relevant cardiovascular, hepatic, neurological, endocrine or other major systemic disease;
* Significantly impaired bone marrow function;
* Pregnant or nursing woman;
* Alcohol or drug abuse;
* Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment;
* Any known condition or circumstance that would prevent in the investigator's opinion compliance or completion of the study;

Answer: D