Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-label Crossover Phase 1 Study to Evaluate the Pharmacokinetic Profiles of BIIB017 (Peginterferon Beta-1a) and Rebif® (Interferon Beta-1a) in Healthy Volunteers
Brief Summary: The primary outcome of the study is to evaluate the cumulative area under the concentration time curve (AUC) over 2 weeks, as measured by AUC from time 0 to 336 hours post dose (AUC0-336h), for serum concentrations of BIIB017 and Rebif.

The secondary outcomes are to evaluate the maximum observed serum concentrations (Cmax) of BIIB017 and Rebif and to evaluate the safety and tolerability of BIIB017 and Rebif over 2 weeks in healthy volunteers.


Options:
A: Inclusion Criteria:

1. Men or women at least 18 years of age or older
2. Subjects must have a confirmed and documented RRMS diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course
3. Subjects must be ambulatory with a Kurtzke Expanded Disability Status Scale (EDSS) score of 0-5.5 in both the Screening and Baseline visits.
4. Subjects must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment \[intravenous (IV), intramuscular (IM) and/or per os (PO)\] or adrenocorticotrophic hormone (ACTH), 60 days prior to randomization.
5. Subjects must be treated with Glatiramer Acetate (GA) 20mg/mL QD SC injection for a minimum of 6 months prior to screening.
6. Women of child-bearing potential must practice an acceptable method of birth control \[acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptives, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy or a double-barrier method (condom or diaphragm with spermicide)\].
7. Subjects must be able to sign and date a written informed consent prior to entering the study.
8. Subjects must be willing and able to comply with the protocol requirements for the duration of the study

Exclusion Criteria:

1. Subject has any contraindication to Glatiramer Acetate therapy
2. Subjects with progressive forms of multiple sclerosis (MS).
3. Subjects with Neuromyelitis Optica (NMO).
4. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
5. Concomitant use of other disease modifying drug for MS ((Fingolimod (Gilenya®), dimethyl fumarate (Tecfidera®), Teriflunomide (Aubagio®) or intravenous immunoglobulin (IVIG)) within 6 months prior to screening
6. Previous use of mitoxantrone, cladribine, alemtuzumab, rituximab, natalizumab.
7. Chronic (more than 30 consecutive days) systemic (IV, PO or IM) corticosteroid treatment within 6 months prior to screening visit.
8. Previous total body irradiation or total lymphoid irradiation.
9. Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
10. Pregnancy or breastfeeding.
11. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical exams, ECG and abnormal laboratory tests. Such conditions may include hepatic, renal or metabolic diseases, systemic disease, acute infection, current malignancy or recent history (5 years) of malignancy, major psychiatric disorder, history of drug and/or alcohol abuse and allergies that could be detrimental according to the investigator's judgment.
12. Subjects who underwent endovascular treatment for Chronic Cerebrospinal Venous Insufficiency (CCSVI).
13. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals -
B: Key Inclusion Criteria:

- Must have a body mass index of 19 to 30 kg/m2, inclusive, and minimum body weight of 45.0 kg at Screening and Day -1

Key Exclusion Criteria:

* History or positive test result at Screening for human immunodeficiency virus, hepatitis C virus antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[HBcAb\])
* History of premalignant and malignant disease including solid tumors and hematologic malignancies
* Known allergy to any interferon or any component of BIIB017
* Prior treatment with any investigational drug within the 30 days prior to Day 1, or within 5 half-lives of the drug, whichever is longer

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: Inclusion Criteria

Patients may be eligible for this study if they:

* Have been diagnosed with RR-MS, within 2 years of diagnosis.
* Are 18-55 years old.
* Have RR-MS with evidence of demyelination on MRI scanning of the brain.
* Have extended disability status scale (EDSS) scores between 0 and 3.5.
* Have not taken Copaxone or oral myelin.
* Have not had immunomodulating therapy for the past 3 months.
* Have not taken immunosuppressants.
* Have not had steroid treatment 1 month before entry.
* Have no evidence of active infection or cancer.

Exclusion Criteria

Patients may not be eligible for this study if they:

* Have a normal brain MRI.
* Are not willing to practice contraception (applies to women who are able to have children).
* Are pregnant or breast-feeding.
* Are currently taking any of the following drugs: beta2-adrenergic agonist or antagonist, diuretics, tricyclic antidepressants, or monoamine oxidase inhibitors.
* Have heart, blood, liver, or kidney problems.
* Have a disease that affects blood clotting or lung function.
* Have abnormalities that relate to the endocrine system.
* Have a history of alcohol or drug abuse within 6 months of enrollment.
* Have been diagnosed with primary progressive MS, in which the disease slowly worsens without periods of recovery.

Answer: B