Expanded

Inclusion Criteria:

1. Relapsing remitting Multiple Sclerosis by 2017 Revised McDonald Criteria. 2. Women aged 45-65 or 40+ post-menopausal. 3. Stable immunomodulatory therapy

• - no switch or planned switch in < 6 months and no change in doses in 30 days prior to screening.

4. Use of contraceptive method with ≤1% failure rate during period of trial if premenopausal. 5. Understand and sign informed consent. 6. EDSS 0-6.0 (inclusive) Chronic Optic Neuropathy Subgroup Inclusion Criteria (including broader inclusion criteria): 1. Expanded inclusion criteria. 2. Latency delay > 118 milliseconds on baseline full-field transient pattern reversal VEP in at least one eye (electrophysiological evidence of demyelination) Expanded

Exclusion Criteria:

1. Multiple Sclerosis disease duration > 25 years. 2. History of significant cardiac conduction block. 3. Patients with a known, suspected or past history of breast, gynecological, or gastrointestinal cancer. 4. Suicidal ideation or behavior in 6 months prior to baseline. 5. Pregnancy, breastfeeding, or planning to become pregnant. 6. Included with other study protocol simultaneously without prior approval. 7. Concomitant or prior use of any other putative remyelinating therapy as determined by investigator, including but not limited to Clemastine, Duavee, and Tamoxifen. 8. Serum creatinine > 1.5mg/dL; AST, ALT, or alkaline phosphatase > 2 times the upper limit of normal. 9. History of drug or alcohol abuse within the past year. 10. Untreated B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid [MMA] and homocysteine) or untreated hypothyroidism. 11. Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal or other major diseases that in the PI's judgement may affect interpretation of study results or patient safety. 12. History of or presence of clinically significant medical illness or laboratory abnormality that, in the opinion of the investigator would preclude participation in the study. 13. Patients whose lack of mobility exposes them to an increased risk of venous thromboembolism. 14. Patients with undiagnosed uterine bleeding. 15. Patients with unknown, suspected or past history of breast cancer. 16. Patients with known or suspected estrogen-dependent neoplasia. 17. Patients with active or a past history of venous thromboembolism. 18. Patients with active or a past history of arterial thromboembolism. 19. Patients with known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders. 20. Patients with hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any ingredients. 21. Patients with known hepatic impairment or disease. Chronic Optic Neuropathy Subgroup

Exclusion Criteria:

1. Expanded exclusion criteria. 2. Optic neuritis in prior 6 months. 3. Known optic neuritis in involved eye ≥ 15 years ago. 4. Major ophthalmologic disease/Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia, etc.). 5. Myopia > -7 Diopters (severe myopia) 6. Disc hemorrhages in qualifying eye. 7. No light perception in qualifying eye. 8. Simultaneous bilateral optic neuritis. 9. Cotton wool spots in qualifying eye. 10. Macular star in qualifying eye

Multiple Sclerosis (MS) is a chronic neurologic disorder characterized by the loss of myelin, which results in disruption of nerve signal, damage to axons, and, ultimately, neurodegeneration. In order to treat MS, new methods for promoting repair (remyelination) are sorely needed. There is a strong preclinical (including EAE) and epidemiologic rationale for investigating the remyelinating potential of estrogenic compounds, including evidence of endogenous (puberty, postpartum periods) and exogenous hormonal influences on MS risk and course. MS affects 3 times more women than men, and disease course in women appears overall less aggressive (on MRI, fewer T2-hyperintense demyelinated lesions develop into axonal destruction visualized as hypointense T1 "black holes"). Bazedoxifene (BZA), a third-generation SERM with extensive safety data in humans, was identified in a novel high-throughput screen (BIMA screen) for compounds capable of promoting remyelination. Subsequent analysis validated BZA's remyelinating effect in vitro and in vivo following demyelinating insult. Given strong pre-clinical support for BZA's remyelinating potential, and the clinical success of other compounds identified using the BIMA screen (Green et al., 2017), the investigators will investigate the use of BZA as a remyelinating therapy in patients with MS.

Arms

Experimental: Group A

Group A is the "early-start" group and will receive a total of 6 months of BZA -- 3 months of BZA, followed by 3 months BZA

Experimental: Group B

Group B is the "delayed-start" group and will receive a total of 3 months of BZA -- 3 months of placebo, followed by 3 months of BZA

Interventions

Drug: - Bazedoxifene Acetate

40 mg Bazedoxifene delivered orally in the form of 2x 20 mg blinded capsules