The purpose of this study is to determine whether MIS416 administered once weekly over 12 months is safe, tolerable, and improves a range of signs and symptoms associated with secondary progressive multiple sclerosis.

The primary objectives of the study are to:

1. Determine the efficacy of MIS416, relative to placebo, when administered repeatedly via weekly intravenous (IV) administration to subjects with Secondary Progressive Multiple Sclerosis, as assessed by its effect on measures of neuromuscular function.
2. Determine the safety and tolerability of a weekly regimen of MIS416.

The secondary objectives of the study are to:

1. Determine the effect of MIS416 on disease activity and neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers including lesions, whole brain atrophy (WBA) and Magnetization Transfer Ratio (MTR).
2. Determine the effect of MIS416 on Patient Reported Outcomes (PRO) related to disability and health status.
3. Assess, in a subset of subjects, the pharmacodynamic (PD) effects of MIS416, including effects on serum, Peripheral Blood Mononuclear Cell (PBMC), and Cerebral Spinal Fluid (CSF) cytokine/chemokine levels and expression patterns.

Inclusion Criteria:

1. A historical or current cranial MRI scan demonstrating T2-hyperintense lesions consistent with MS.

2. Has SPMS as determined by the 2010 Update to the McDonald Criteria

3. An Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 at Screening.

4. Has SPMS which, in the judgment of the investigator, has been clinically active and functionally progressive within the 2 years prior to Screening

5. The absence of MS relapse for at least two years prior to Baseline.

6. Neurologically stable for at least four weeks prior to Screening.

7. Has the following laboratory values within three days prior to initiation of Investigational Product:

   • Absolute neutrophil count (ANC) >= 1 x 109/L;
   • Platelet count >= 100 x 109/L;
   • Serum creatinine =< 1.5 mg/dL;
   • Aspartate aminotransferase (AST) =<2 × upper limit of normal;
   • Alanine aminotransferase (ALT) =< 2 × upper limit of normal.

8. Provided written informed consent to participate.

Exclusion Criteria:

1. Has primary Progressive MS (PPMS), Relapsing Remitting (RRMS), or progressive relapsing MS as determined by the 2010 update to the McDonald Criteria.
2. Has not completed the discontinuation period for approved and/or investigational multiple sclerosis disease modifying therapies prior to screening.
3. Has had any other immunomodulatory drug therapy or immunosuppressive therapy within four weeks prior to Screening, or systemic corticosteroids within the eight weeks prior to Screening.
4. Any previous exposure to investigational MS therapeutic vaccines.
5. Any use of cell-depleting monoclonal antibodies including, but not limited to, Rituximab, or Ocrelizumab.
6. A diagnosis or history of collagen vascular disease (including Sjögren's syndrome and systemic lupus erythematosus), anticardiolipin antibody syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, sarcoidosis, vasculitis, Behcet's syndrome and/or Lyme disease.
7. Contraindication to MRI (e.g., pacemaker or other contraindicated implanted metal device, allergy to gadolinium, or unmanageable claustrophobia).
8. A history of alcohol or drug abuse (including cannabinoid use) within two years prior to Screening.
9. Has had major surgery or radiation therapy within four weeks prior to Screening.
10. Has an active infection requiring antibiotics within two weeks prior to Screening.
11. Has had active malignancy within two years of Screening, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin.
12. Uncontrolled congestive heart failure, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack within twelve weeks prior to Screening.
13. Has angina, other symptomatic coronary artery disease, or known cardiomyopathy.
14. Has symptomatic cardiac dysrhythmias requiring treatment, or persistent prolongation of the QTcF (Fredericia) interval to > 450 msec for males or > 470 msec for females.