Summary

for females ages 40-65 (full criteria)
at San Francisco, California
study started
estimated completion
Riley Bove

Description

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.

Official Title

A Phase II Randomized, Double-Blind, Parallel-Group, Placebo Controlled Delayed-Start Trial to Assess the Efficacy, Safety, and Tolerability of Bazedoxifene Acetate (BZA) as a Remyelinating Agent in Patients With Multiple Sclerosis

Details

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.

Keywords

Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting MS RRMS Remyelination Repair SERM Estrogen BZA Bazedoxifene Myelin Repair Conbriza Sclerosis Bazedoxifene Acetate

Eligibility

You can join if…

Open to females ages 40-65

  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)

You CAN'T join if...

  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

Location

  • Weill Institute for Neurosciences, University of California, San Francisco accepting new patients
    San Francisco California 94158 United States

Lead Scientist

  • Riley Bove
    Assistant Professor, Neurology. Authored (or co-authored) 74 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Riley Bove, MD
Links
Bove Lab
https://multiplesclerosis.ucsf.edu/research
ID
NCT04002934
Phase
Phase 2
Study Type
Interventional
Last Updated