Efficacy and Safety of BIIB033 (Opicinumab) as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS)

Key Inclusion Criteria: Part 1

* Baseline Expanded Disability Status Scale (EDSS) of 2.0 to 6.0, have a diagnosis of relapsing-remitting multiple sclerosis (RRMS) per the 2010 McDonald's criteria or onset of secondary progressive multiple sclerosis (SPMS) per the Lublin and Reingold criteria, and should have experienced their first MS symptom(s) within the previous 20 years.
* Subjects must have experienced at least 1 of the following within 24 months prior to Day 1/Baseline: a clinical relapse (but not within 24 weeks prior to Day 1/Baseline), gadolinium-enhancing lesions on brain or spinal cord magnetic resonance imaging (MRI), or new T2 lesion(s) on brain or spinal cord MRI.
* Subjects must be on a stable dose of a protocol-specified anti-inflammatory disease-modifying therapy (DMT) (IFNβ \[Avonex, Plegridy, Betaferon/Betaseron, or Rebif\], dimethyl fumarate (DMF) \[Tecfidera\], or natalizumab \[Tysabri\]) for at least 24 weeks prior to enrollment.
* In addition, subjects must have met protocol-defined MRI characteristics using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) sequences at Screening/Baseline.

Key Inclusion Criteria: Part 2

-Subjects who complete study treatment (BIIB033 or placebo) at Part 1/Week 72 Visit.

Key Exclusion Criteria: Part 1

* Primary progressive MS
* An MS relapse that has occurred within 24 weeks prior to Day 1/Baseline or the subject has not stabilized from a previous relapse at the time of Screening.
* Treatment with any chemotherapeutic agents (e.g., mitoxantrone, cyclophosphamide, cladribine), cell-depleting monoclonal antibodies (mAbs) (e.g., rituximab, ocrelizumab, alemtuzumab), total lymphoid irradiation, T-cell or T-cell receptor vaccination, or teriflunomide within 1 year prior to Day 1/Baseline.
* Treatment with other anti-inflammatory DMTs (e.g., GA, fingolimod, daclizumab) or plasmapheresis within 24 weeks prior to Day1/Baseline.
* Treatment with Botox for limb spasticity within 24 weeks before Day 1/Baseline.
* Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to gadolinium renal impairment, or claustrophobia that cannot be medically managed.
* History of human immunodeficiency virus or other immunodeficient conditions.
* History of malignancy; however, subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.

Key Exclusion Criteria: Part 2

* Subjects who did not complete study treatment in Part 1/Week 72 Visit
* Subjects who have a duration \>12 weeks between their Part 1/Week 72 Visit and Part 2/Day 1.
* Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to Gd, renal impairment, or claustrophobia that cannot be medically managed.
* History of human immunodeficiency virus or other immunodeficient conditions not related to DMT treatment.
* History of malignancy unless enrollment is approved by the Sponsor; subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply