Bazedoxifene Acetate as a Remyelinating Agent in Multiple Sclerosis (ReWRAP)

November 14, 2023 updated by: Riley Bove, MD

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94158
        • Recruiting
        • Weill Institute for Neurosciences, University of California, San Francisco
        • Principal Investigator:
          • Riley Bove, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: Bazedoxifene Acetate
40 mg Bazedoxifene delivered orally in the form of 2x 20 mg blinded capsules
Other Names:
  • Viviant
  • Bazedoxifene
  • Conbriza
  • TSE-424
  • WAY 140424
  • WAY-140424
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
Drug: Bazedoxifene Acetate
40 mg Bazedoxifene delivered orally in the form of 2x 20 mg blinded capsules
Other Names:
  • Viviant
  • Bazedoxifene
  • Conbriza
  • TSE-424
  • WAY 140424
  • WAY-140424

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
P100 Latency on Full Field Visual Evoked Potential
Time Frame: 3 months
The primary objective is to evaluate the efficacy of BZA relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials (VEPs). In response to a visual stimulus, cortically generated electrical potentials (VEPs) recorded over the scalp are used to measure the functional integrity of visual pathways.
3 months
P100 Latency on Full Field Visual Evoked Potential
Time Frame: 6 months
Assess whether P100 latency delay at 6 months decreases to a greater extent in Group A (exposed to BZA for 3 months during both Stage 1 and Stage 2 -- 6 months total) when compared to Group B (exposed to placebo during Stage 1 and BZA for 3 months during Stage 2 -- 3 months total).
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Riley Bove, MD

Investigators

  • Principal Investigator: Riley M Bove, MD MMSc, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 10, 2019

Primary Completion (Estimated)

February 15, 2024

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

June 25, 2019

First Submitted That Met QC Criteria

June 26, 2019

First Posted (Actual)

July 1, 2019

Study Record Updates

Last Update Posted (Actual)

November 15, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ReWRAP
  • 138495 (Other Identifier: FDA -- Investigational New Drug Number)
  • 18-24511 (Other Identifier: UCSF IRB No.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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