Bazedoxifene Acetate as a Remyelinating Agent in Multiple Sclerosis

Criteria the registry did not label

• Expanded Inclusion Criteria:
• Relapsing remitting Multiple Sclerosis by 2017 Revised McDonald Criteria
• Women aged 45-65 or 40+ post-menopausal.
• Stable immunomodulatory therapy - no switch or planned switch in \< 6 months and no change in doses in 30 days prior to screening
• Use of contraceptive method with ≤1% failure rate during period of trial if premenopausal
• Understand and sign informed consent.
• EDSS 0-6.0 (inclusive)
  • Chronic Optic Neuropathy Subgroup Inclusion Criteria (including broader inclusion criteria):
• Expanded inclusion criteria
• Latency delay \> 118 milliseconds on baseline full-field transient pattern reversal VEP in at least one eye (electrophysiological evidence of demyelination)
  • Expanded Exclusion Criteria:
• Multiple Sclerosis disease duration \> 25 years
• History of significant cardiac conduction block
• Patients with a known, suspected or past history of breast, gynecological, or gastrointestinal cancer
• Suicidal ideation or behavior in 6 months prior to baseline
• Pregnancy, breastfeeding, or planning to become pregnant
• Included with other study protocol simultaneously without prior approval
• Concomitant or prior use of any other putative remyelinating therapy as determined by investigator, including but not limited to Clemastine, Duavee, and Tamoxifen.
• Serum creatinine \> 1.5mg/dL; AST, ALT, or alkaline phosphatase \> 2 times the upper limit of normal
• History of drug or alcohol abuse within the past year
• Untreated B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid \[MMA\] and homocysteine) or untreated hypothyroidism
• 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.
• 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.
• Patients whose lack of mobility exposes them to an increased risk of venous thromboembolism
• Patients with undiagnosed uterine bleeding
• Patients with unknown, suspected or past history of breast cancer
• Patients with known or suspected estrogen-dependent neoplasia
• Patients with active or a past history of venous thromboembolism
• Patients with active or a past history of arterial thromboembolism
• Patients with known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders
• Patients with hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any ingredients
• Patients with known hepatic impairment or disease
  • Chronic Optic Neuropathy Subgroup Exclusion Criteria:
• Expanded exclusion criteria
• Optic neuritis in prior 6 months
• Known optic neuritis in involved eye ≥ 15 years ago
• Major ophthalmologic disease/Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia, etc.).
• Myopia \> -7 Diopters (severe myopia)
• Disc hemorrhages in qualifying eye
• No light perception in qualifying eye
• Simultaneous bilateral optic neuritis
• Cotton wool spots in qualifying eye
• Macular star in qualifying eye