Please select the eligibility criteria that correspond to the clinical trial below.
Title: Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis
Brief Summary: This study aims to evaluate safety and efficacy of dimethyl fumarate treatment in patients with primary progressive multiple sclerosis (PPMS).

Half of the patients will receive dimethyl fumarate and the other half will receive placebo.


Options:
A: Inclusion Criteria:

* Male or female age 18 to 55 years, inclusive.
* Diagnosis of MS by McDonald criteria.
* EDSS \<7.0.
* On stable IFN-beta regimen for at least 6 months.
* The occurrence of either of the following within 9 months prior to screening: ≥1 MS relapse OR A qualifying MRI, defined as an MRI that showed at least one confirmed Gd-CEL of the brain or spinal cord, was performed independently of the study while the patient was on a stable IFN-beta regimen, and is deemed acceptable by the central reader.
* For females, women of non-childbearing potential or women of childbearing potential who provide a negative serum pregnancy test at screen and within 24 hours of first dose of study drug, and who agree to use effective contraception during the Treatment and Follow-up periods of the study.
* Willing and able to comply with the protocol, provision of informed consent in accordance with institutional and regulatory guidelines, and, for US sites only, authorization to use protected health information.

Exclusion Criteria:

* Pregnant or breast-feeding woman.
* Non-ambulatory patient.
* Clinically significant abnormality on screening ECG.
* Malignancy within the past 5 years, except for adequately treated non-melanoma skin carcinoma or in situ carcinoma of the cervix.
* History of HIV infection, positive serology for HBV (hepatitis B virus) or HCV (hepatitis C virus).
* Varicella (VZV) or herpes zoster virus infection, or any severe viral infection, within 6 weeks before screening or exposure to VZV within 21 days of screening.
* Abnormal hematology, as defined by the following laboratory values: \*Hemoglobin ≤8.5 g/dL, \*Lymphocytes ≤1.0 x 10\^9/L, \*Platelets ≤100 x 10\^9/L, \*Neutrophils ≤1.5 x 10\^9/L.
* Significant organ dysfunction, including but not limited to cardiac, renal, liver, non-MS related CNS, pulmonary, vascular, gastrointestinal, endocrine, or metabolic dysfunction, or other disease or condition, which in the opinion of the PI (principal investigator) would make the patient an unsuitable candidate for the study. Guidelines for levels of unacceptable dysfunction include: \*creatinine ≥1.6 mg/dL; \*AST and ALT ≥2.5 times upper limit of normal (ULN); \*alkaline phosphatase ≥2.5 times ULN; \*history of myocardial infarction, congestive heart failure, or arrhythmias within 6 months prior to randomization.
* Use of any of the following: \*Any of the following types of live virus vaccine from 4 weeks before randomization: measles/mumps/rubella vaccine, varicella zoster virus vaccine, oral polio vaccine, and nasal influenza vaccine. Use of these vaccines, however, by household contacts does not affect the eligibility of patients to enroll or continue in the study; \*Systemic corticosteroids, adrenocorticotropic hormone, or plasma exchange within 4 weeks before the baseline MRI scan (no more than 72 hours before Day 0); \*Azathioprine, mycophenolate mofetil, methotrexate, glatiramer acetate, or intravenous immune globulin within 6 months before randomization; \*An immunomodulatory agent within 6 months before randomization, except for interferon-beta products required per protocol; \*An investigational agent within 6 months before randomization unless this agent is non-immunomodulatory and the medical monitor or steering committee rules that its use is acceptable on the theoretical basis of a lapse of at least 5 serum half-lives since administration of the last possible dose; \*A monoclonal antibody (eg, Rituxan®/ Rituximab) within 6 months before randomization; \*Daclizumab at any time prior to randomization; \*Cladribine, mitoxantrone, cyclophosphamide, CamPath® (alemtuzumab), natalizumab (TYSABRI®/Antegren) or other drugs targeting alpha 4 integrin, total lymphoid irradiation, or bone marrow transplant at any time
* Patients for whom MRI is contraindicated, ie, have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed.
* Primary progressive MS.
* Clinically unstable for 30 days before randomization (Patients who experienced a relapse, with or without steroid treatment, during the screening period may be re-screened after 30 days.)
* Elective surgery performed from 2 weeks prior to randomization or scheduled through Week 44
* Infection (viral, fungal, bacterial) requiring hospitalization or IV antibiotics within 8 weeks before randomization.
B: Key Inclusion Criteria:

* Must have a confirmed diagnosis of Relapsing Remitting Multiple Sclerosis (RRMS), and a cranial magnetic resonance imaging (MRI) demonstrating lesion(s) consistent with MS
* Must have a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive
* Male subjects and female subjects of childbearing potential must be willing to practice effective contraception during the study and be willing and able to continue contraception for 4 months after their last dose of study treatment

Key Exclusion Criteria:

* Known intolerance, contraindication to, or history of non-compliance with Avonex® 30 µg
* History of treatment with Daclizumab High Yield Process (Dac HYP)
* History of malignancy
* History of severe allergic or anaphylactic reactions
* Known hypersensitivity to study drugs or their excipients
* History of abnormal laboratory results indicative of any significant disease
* History of human immunodeficiency virus (HIV) or other immunodeficient conditions
* History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to randomization
* History of seizure disorder or unexplained blackouts OR history of a seizure within 6 months prior to Baseline
* History of suicidal ideation or an episode of clinically severe depression (as determined by the Investigator) within 3 months prior to Day 1
* An MS relapse that has occurred within the 50 days prior to randomization AND/OR the subject has not stabilized from a previous relapse prior to randomization
* Known history of, or positive screening test result for hepatitis C virus or hepatitis B virus
* Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before screening
* Exposure to varicella zoster virus within 21 days before screening

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

* Age 18 to 65 years
* PPMS according to the McDonald (2010) and Lublin (2014) criteria
* Disease duration at least one year
* EDSS ≤ 6.5
* Written informed consent to study participation
* No other signs of significant disease judged by the investigator
* Eligible for randomization to active treatment or placebo as assessed by CSF NFL levels above 380ng/L
* Not eligible for randomization as assessed by CSF biomarker studies but accepts follow-up and open-label treatment per protocol
* Patients not eligible for randomization due to low NFL concentrations in CSF at screening can be followed up after 48 weeks, and are eligible for open-label treatment if they fulfil one of the following clinical criteria of disease progression:
* 1 point increase in EDSS score from screening to week 48 if screening EDSS \<6
* 0.5 point increase in EDSS score from screening to week 48 if screening EDSS\>5.5
* 2 point increase in a physical functional system
* Worsening in SDMT, 9HPT or T25FW \>20% from screening to week 48

Exclusion Criteria:

* Pregnancy or breast feeding
* Lack of effective contraception for women of child-bearing potential
* Relapse within 6 months of inclusion
* Methylprednisolone treatment within 3 months of inclusion
* Treatment with interferon-beta, glatiramer acetate, immunoglobulin G or other immunomodulatory treatment within 6 months of inclusion
* Treatment with mitoxantrone, cyclophosphamide, azathioprine or other immunosuppressive treatment within 6 months of inclusion
* Findings on the screening MRI judged to preclude participation by the treating physician
* Other diseases associated with immunodeficiency
* Other diseases judged to be relevant by the treating physician
* Anticoagulant therapy other than platelet inhibitors
* Active malignant disease in the previous 5 years
* Renal insufficiency or blood creatinine \> 150 μmol/l
* Present or chronic infection with hepatitis B virus, hepatitis C virus, HIV (tested in the screening blood samples) or other infections found to be relevant by the treating physician.
* Psychiatric disorders or other disorders impairing the patient's ability to participate in the trial
* Contraindication to MRI
* Known allergy or hypersensitivity to dimethyl fumarate
D: Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of the randomization:

Key Inclusion Criteria:

* Must have confirmed diagnosis of RRMS according to McDonald criteria #1-4
* Must have a baseline EDSS between 0.0 and 5.0, inclusive.
* Must have relapsing-remitting disease course.

Key Exclusion Criteria:

* Other chronic disease of immune system, malignancies, urologic, pulmonary, gastrointestinal disease
* Pregnant or nursing women

Note: Other protocol-defined inclusion/exclusion criteria may apply.

Answer: C