Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-Label, Single-Arm Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Early Stage Relapsing Remitting Multiple Sclerosis
Brief Summary: This is a prospective, multicenter, open-label, single-arm, phase 3b study which evaluates effectiveness and safety of ocrelizumab in participants with early stage RRMS. The study will consist of an open-label treatment period of 192 weeks and follow-up period of at least 48 weeks.

The optional shorter infusion substudy will evaluate the safety of a shorter infusion of ocrelizumab in a subgroup of participants with early stage RRMS enrolled in the main MA30143 study. Approximately 700 patients will be enrolled in the substudy, and will receive additional 600 mg ocrelizumab administered in a shorter time frame.


Options:
A: Inclusion Criteria:

1. Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria \[Ann Neurol 2005: 58:840-846\], with a relapsing-remitting disease course.
2. Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.
3. Subjects must be in a stable neurological condition and free of corticosteroid treatment \[intravenous (iv), intramuscular (im) and/or per os (po)\] 30 days prior to screening (month -1).
4. Subjects must have had experienced one of the following:

   * At least one documented relapse in the 12 months prior to screening
   * At least two documented relapses in the 24 months prior to screening
   * One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening.
5. Subjects must be between 18 and 55 years of age, inclusive.
6. Subjects must have disease duration of at least 6 months (from the first symptom) prior to screening.
7. 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 contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide).
8. Subjects must be able to sign and date a written informed consent prior to entering the study
9. Subjects must be willing and able to comply with the protocol requirements for the duration of the study.

Exclusion Criteria:

1. Subjects with progressive forms of MS
2. An onset of relapse, unstable neurological condition or any treatment with corticosteroids \[intravenous (iv), intramuscular (im) and/or per os (po)\] or ACTH between month -1 (screening) and 0 (baseline).
3. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
4. Use of immunosuppressive including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit.
5. Previous use of either of the following: natalizumab (Tysabri®), cladribine, laquinimod.
6. Previous treatment with glatiramer acetate (Copaxone®) Interferon-β (either 1a or 1b) or IVIG within 2 months prior to screening visit.
7. Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 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. A known history of tuberculosis.
11. Acute infection two weeks prior to baseline visit.
12. Major trauma or surgery two weeks prior to baseline
13. A history of vascular thrombosis (excluding catheter-site superficial venous thrombophlebitis).
14. A carrier state of factor V Leiden mutation (either homo- or heterozygous) as disclosed at screening.
15. Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV antibody as disclosed at screening visit.
16. Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (1 month for fluoxetine) see detailed list in Appendix 5
17. Use of amiodarone within 2 years prior to screening visit.
18. Pregnancy or breastfeeding.
19. 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 examinations, ECG, laboratory tests or chest X-ray. Such conditions may include:

    * A cardiovascular or pulmonary disorder that cannot be well-controlled by standard treatment permitted by the study protocol.
    * A gastrointestinal disorder that may affect the absorption of study medication.
    * Renal or metabolic diseases.
    * Any form of chronic liver disease, including known non-alcoholic steatohepatitis.
    * A ≥2xULN serum elevation of either of the following at screening: ALT, AST or direct bilirubin
    * A QTC interval (obtained from either 2 ECG recordings at screening or from the mean value calculated from 3 measurements at baseline visit) which is \>450msec.
    * A family history of Long- QT syndrome.
    * A history of drug and/or alcohol abuse.
    * Major psychiatric disorder.
20. A known history of sensitivity to Gd.
21. Inability to successfully undergo MRI scanning.
22. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.

Exclusion Criteria:

1. Subjects who suffer from any form of progressive MS.
2. Any condition which the investigator feels may interfere with participation in the study.
3. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation,
4. Subjects who received any investigational medication, immunosuppressives or cytotoxic agents within 6 months prior to screening
5. Previous treatment with immunomodulators within two months prior to screening
6. Pregnancy or breastfeeding.
B: Inclusion Criteria:

* Have a definite diagnosis of RRMS, as per the revised McDonald 2010 criteria
* Have a length of disease duration, from first documented clinical attack consistent with MS disease of less than or equal to (\</=) 3 years
* Within the last 12 months one or more clinically reported relapse(s) or one or more signs of MRI activity
* EDSS of 0.0 to 3.5 inclusive, at screening
* An agreement to use an acceptable birth control method for women of childbearing potential, during the treatment period and for at least 6 months or longer after the last dose of study drug

Exclusion Criteria:

* Secondary progressive multiple sclerosis or history of primary progressive or progressive relapsing MS
* Inability to complete an MRI
* Known presence of other neurological disorders

Exclusions Related to General Health:

* Pregnancy or lactation
* Participants intending to become pregnant during the study or within 6 months after the last dose of the study drug
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History or currently active primary or secondary immunodeficiency
* Lack of peripheral venous access
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
* Significant or uncontrolled somatic disease or any other significant disease that may preclude participant from participating in the study
* Congestive heart failure (New York Heart Association III or IV functional severity)
* Known active bacterial, viral, fungal, mycobacterial infection or other infection, (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to screening or oral antibiotics 2 weeks prior to screening
* History of malignancy, major opportunistic infections, alcohol or drug abuse, recurrent or chronic infection, and/or coagulation disorders

Exclusions Related to Medications:

* Received any prior approved disease modifying treatment (DMT) with a label for MS, for example, interferons, glatiramer acetate, natalizumab, alemtuzumab, daclizumab, fingolimod, teiflunomide and dimethylfumarate
* Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit
* Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
* Any previous treatment with immunosuppressants/ immunomodulators/ antineoplastic therapies (cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, cladribine, mitoxantrone, laquinimod, total body irradiation, or bone marrow transplantation)
* Treatment with investigational DMT
* Treatment with fampridine/dalfamipridine unless on stable dose for \>/=30 days prior to screening

Exclusion related to Shorter Infusion Substudy:

- Any previous serious IRRs experienced with ocrelizumab treatment
C: 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
D: Inclusion Criteria:

* Participants with a diagnosis of relapsing multiple sclerosis (may include participants with Secondary Progressive Multiple Sclerosis (SPMS) with superimposed relapses provided they meet the other criteria) in accordance with revised McDonald criteria for MS and Lublin and Reingold
* Male or female aged 18 to 65 years
* One or more documented relapses within the 2 years before Screening with either: a) One relapse which occurred within the last year prior to randomization or b) the presence of at least 1 gadolinium-positive (Gd+) T1 lesion within 6 months prior to randomization would make the patient eligible.
* Expanded Disability Status Scale score of 0 to 6 at Baseline
* Women of childbearing potential must use a supplementary barrier method together with a highly effective method of contraception (according to International Council for Harmonisation \[ICH\] guidance M3\[R2\]) for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of IMP.
* Signed and dated informed consent (participant must be able to understand the informed consent) indicating that the participant has been informed of all the pertinent aspects of the trial prior to enrolment and will comply with the requirements of the protocol.

Exclusion Criteria:

* Progressive MS
* Disease duration \> 15 years in participants with EDSS of 2 or less
* Use of the following, as determined in the protocol ; rituximab, ocrelizumab, mitoxantrone, or lymphocyte-depleting therapies, lymphocyte trafficking blockers (eg, natalizumab, fingolimod), intravenous (IV) immunoglobulins (Ig), plasmapheresis, immunosuppressive treatments, B-interferons or glatiramer acetate, Systemic glucocorticoids, teriflunomide
* Exposure to Tecfidera within 6 months prior to randomization
* Any allergy, contraindication, or inability to tolerate Tecfidera
* Treatment with dalfampridine (fampridine, Ampyra) unless on a stable dose for ≥ 30 days prior to randomization
* Inability to comply with MRI scanning
* Immunologic disorder other than MS, with the exception of secondary well-controlled diabetes or thyroid disorder, or any other condition requiring oral, IV, intramuscular, or intra-articular corticosteroid therapy
* Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
* Severe drug allergy or history of anaphylaxis, or allergy to the IMP or any of its incipients
* Active, clinically significant viral, bacterial, or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of Screening, or completion of oral anti-infectives within 2 weeks before or during Screening, or a history of recurrent infections (ie, 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary.
* History of or positive testing for human immunodeficiency virus (HIV), hepatitis C (HCV) antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg) (+) and/or hepatitis B core total, and/or immunoglobulin M (IgM) antibody (+) at Screening.
* The participant: • Has a history of or current diagnosis of active tuberculosis (TB) or • Is currently undergoing treatment for latent TB infection (LTBI) or • Has an untreated LTBI or • Has a positive QuantiFERON®-TB test at Screening.
* Indeterminate QuantiFERON®
* Participants with current household contacts with active TB will also be excluded
* History of splenectomy or any major surgery within 2 months prior to Screening
* History of myocardial infarction or cerebrovascular event as per the protocol
* History of attempted suicide within 6 months prior to Screening or a positive response to items 4 or 5 of Columbia-Suicide Severity Rating Scale (C-SSRS)
* An episode of major depression within the last 6 months prior to Screening
* On anticoagulation, fish oil supplements, or antiplatelet therapy other than daily aspirin for cardioprotection and treatment of Tecfidera induced flushing
* History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin
* Breastfeeding/lactating or pregnant women
* Participation in any investigational drug trial within 1 month or 5 half-lives of the investigational drug, whichever is longest, prior to Screening
* Participants currently receiving (or unable to stop using prior to receiving the first dose of IMP) medications or herbal supplements known to be potent inhibitors of cytochrome P450 3A (CYP3A)
* History of or current alcohol or substance abuse
* Clinically significant abnormality on electrocardiogram or screening chest X-ray
* Clinically significant laboratory abnormality

Answer: B