Bazedoxifene Acetate as a Remyelinating Agent in Multiple Sclerosis

NCT04002934 | Completed Phase 2 FDA Drug

• 3 other identifiers: ReWRAP13849518-24511
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Keywords

MS; RRMS; Remyelination; Repair; Multiple Sclerosis; SERM; Estrogen; BZA; Bazedoxifene; Myelin Repair; Conbriza

Outcome Measures

Primary Outcomes (1)

• Myelin Water Fraction (MWF) on MRI

  The primary objective is to evaluate the efficacy of BZA relative to placebo for increasing MWF on MRI within normal appearing white matter of the corpus callosum, between baseline and 90 days in a double-blinded trial (1st 90 days in the early start group versus 1st 90 days of the delayed start group).

  3 months

Secondary Outcomes (23)

• Changes in BICAMS scores

  3 months

• Changes in MSFC scores

  3 months

• Changes in BICAMS scores

  6 months

• Changes in MSFC scores

  6 months

• Myelin Water Fraction (MWF) on MRI

  6 months

Other Outcomes (6)

• Tolerability and Safety of BZA - Patient Hot Flash Diary

  6 months

• Tolerability and Safety of BZA - Treatment Satisfaction Questionnaire for Medication (TSQM)

  6 months

• Tolerability and Safety of BZA - Patient Reports of Spasms

  6 months

Study Arms (2)

Group A

EXPERIMENTAL

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

Group B

EXPERIMENTAL

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

Interventions

Bazedoxifene Acetate DRUG

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

Also known as: Bazedoxifene, Conbriza, Viviant, TSE-424, WAY 140424, WAY-140424

Group A; Group B

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Riley Bove, MD: lead

Study Sites (1)

Weill Institute for Neurosciences, University of California, San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (3)

• Green AJ, Gelfand JM, Cree BA, Bevan C, Boscardin WJ, Mei F, Inman J, Arnow S, Devereux M, Abounasr A, Nobuta H, Zhu A, Friessen M, Gerona R, von Budingen HC, Henry RG, Hauser SL, Chan JR. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet. 2017 Dec 2;390(10111):2481-2489. doi: 10.1016/S0140-6736(17)32346-2. Epub 2017 Oct 10.

  PMID: 29029896 BACKGROUND

• Nylander A, Anderson A, Rowles W, Hsu S, Lazar AA, Mayoral SR, Pease-Raissi SE, Green A, Bove R. Re-WRAP (Remyelination for women at risk of axonal loss and progression): A phase II randomized placebo-controlled delayed-start trial of bazedoxifene for myelin repair in multiple sclerosis. Contemp Clin Trials. 2023 Nov;134:107333. doi: 10.1016/j.cct.2023.107333. Epub 2023 Sep 20.

  PMID: 37739167 DERIVED

• Morales-Rodriguez D, Anderson A, Nylander A, Hsu S, Singh J, Rowles W, Walsh CM, Braley TJ, Bove R. Well-being at midlife: Correlates of mental health in ambulatory menopausal women with multiple sclerosis. Mult Scler. 2023 Oct;29(11-12):1493-1502. doi: 10.1177/13524585231197056. Epub 2023 Sep 16.

  PMID: 37715710 DERIVED

Related Links

• Bove Lab
• UCSF Health

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Interventions

bazedoxifene

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Riley M Bove, MD MMSc

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Model Details: This is a randomized, placebo controlled, double-blind, delayed-start trial of BZA in 50 women with MS to be given as follows: Group A will receive 3 months of BZA + 3 months of BZA; Group B will receive 3 months of placebo + 3 months of BZA

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: July 1, 2019
• Study Start: September 10, 2019
• Primary Completion: May 13, 2025
• Study Completion: May 20, 2025
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)