Efficacy and Safety of BIIB033 (Opicinumab) as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS)
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: BIIB033 (opicinumab); Placebo
Intervention description: Administered as specified in the treatment arm; Administered as specified in the treatment arm
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 263.0
Sex: All
Minimum age: 18 Years
Maximum age: 58 Years
Healthy volunteers: No
Keywords: Remyelination; Re-myelination; DMT; LINGO-1; Anti-LINGO-1; Opicinumab

Summary:

      The primary objective of Part 1 of this study is to evaluate the effects of BIIB033 versus
      placebo on disability improvement over 72 weeks. The primary objective of Part 2 of this
      study is to evaluate the long-term safety profile of BIIB033 as an add-on therapy in
      participants with MS.

      The secondary objective of Part 1 is to evaluate the effects of BIIB033 versus placebo on
      additional measures of disability improvement. The secondary objective of Part 2 is to
      investigate long-term efficacy (disability improvement) and additional safety measures of
      BIIB033 as an add-on therapy in participants with MS.
    

Eligibility criteria:

        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