Bazedoxifene Acetate as a Remyelinating Agent in Multiple Sclerosis

• Status: Recruiting
• Trial end date: 2022-08-31
• Target enrollment: 0
• Participant gender: Female

Summary

The primary goal of this study is to assess the efficacy of bazedoxifene (BZA) as remyelinating agent in patients with relapsing-remitting multiple sclerosis (RRMS).

The investigators will utilize electrophysiologic techniques and magnetic resonance imaging to quantify the effect of treatment in 50 women over the course of 6 months.

Participants may remain on their standard disease modifying treatment during the course of the trial but may not concurrently participate in any other investigational new drug research study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Riley Bove, MD; University of California, San Francisco
• Treatments: Bazedoxifene

Criteria

Inclusion Criteria:

1. Women aged 45-65 or 40+ post-menopausal.

2. Documentation of a clinically definite diagnosis of relapsing-remitting MS

3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

4. Latency delay > 118 milliseconds on baseline full-field transient pattern reversal VEP in at least one eye (electrophysiological evidence of demyelination)

5. RNFL > 70 microns on SD-OCT in the same eye meeting criteria for latency delay (sufficient axons)

6. Stable immunomodulatory therapy - no switch or planned switch in > 6 months and no change in doses in 30 days prior to screening

7. Use of contraceptive method with ≤1% failure rate during period of trial if premenopausal

8. Understand and sign informed consent.

9. EDSS 0-6.0 (inclusive)

Exclusion Criteria:

1. Multiple Sclerosis disease duration > 25 years

2. Optic neuritis in prior 6 months

3. Known optic neuritis in involved eye ≥ 10 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

11. History of significant cardiac conduction block

12. History of cancer (except non-melanoma skin cancer)

13. Suicidal ideation or behavior in 6 months prior to baseline

14. Pregnancy, breastfeeding, or planning to become pregnant

15. Included with other study protocol simultaneously without prior approval

16. Concomitant or prior use of any other putative remyelinating therapy as determined by investigator, including but not limited to Clemastine, Duavee, and Tamoxifen.

17. Serum creatinine > 1.5mg/dL; AST, ALT, or alkaline phosphatase > 2 times the upper limit of normal

18. History of drug or alcohol abuse within the past year

19. Untreated B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid [MMA] and homocysteine) or untreated hypothyroidism

20. 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.

21. 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.

22. Patients whose lack of mobility exposes them to an increased risk of venous thromboembolism

23. Patients with undiagnosed uterine bleeding

24. Patients with unknown, suspected or past history of breast cancer

25. Patients with known or suspected estrogen-dependent neoplasia

26. Patients with active or a past history of venous thromboembolism

27. Patients with active or a past history of arterial thromboembolism

28. Patients with known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders

29. Patients with hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any ingredients

30. Patients with known hepatic impairment or disease