Bazedoxifene Acetate for Multiple Sclerosis

(ReWRAP Trial)

Overseen By Ayushi Balan

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Riley Bove, MD

Must not be taking: Clemastine, Duavee, Tamoxifen, others

Disqualifiers: Cancer, Pregnancy, Thromboembolism, Cardiac block, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

62 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You can continue taking your standard disease-modifying treatment during the trial, but you cannot participate in any other investigational drug studies at the same time.

What data supports the effectiveness of the drug Bazedoxifene Acetate for treating multiple sclerosis?

Research suggests that Bazedoxifene Acetate may help repair myelin (the protective covering of nerves) in multiple sclerosis, as it has shown remyelinating effects in pre-clinical models. Additionally, in a spinal cord injury model, it promoted nerve protection and recovery, indicating potential benefits for similar nerve-related conditions. ^{1 2 3 4 5}

How does the drug Bazedoxifene Acetate differ from other multiple sclerosis treatments?

Bazedoxifene Acetate is unique because it is primarily known as a selective estrogen receptor modulator (SERM) used for osteoporosis, and its application in multiple sclerosis is novel, potentially offering a different mechanism of action compared to traditional MS treatments like interferon beta-1a and glatiramer acetate, which are more established in managing the disease. ^{6 7 8 9 10}

Research Team

Riley Bove, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for women aged 45-65 with relapsing-remitting multiple sclerosis (RRMS) who have been on stable immunomodulatory therapy. They must not be pregnant, planning pregnancy, or breastfeeding and should use effective contraception. Participants cannot have severe myopia, a history of certain cancers or thromboembolism, untreated B12 deficiency or hypothyroidism, significant cardiac issues, or drug/alcohol abuse in the past year.

Inclusion Criteria

My immune therapy has been stable for over 6 months with no dose changes in the last 30 days.

My disability level allows me to walk at least with a cane.

My eye test shows enough nerve fibers.

Exclusion Criteria

I have a known liver condition.

My cancer is or might be fueled by estrogen.

I have had or currently have blood clots in my veins.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Bazedoxifene Acetate (BZA) as a remyelinating agent. Group A receives 6 months of BZA, while Group B receives 3 months of placebo followed by 3 months of BZA.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment using various assessments including MRI, patient-reported outcomes, and safety monitoring.

4-8 weeks

Treatment Details

Interventions

• Bazedoxifene Acetate

Trial Overview The study tests bazedoxifene acetate's ability to repair nerve insulation (remyelination) in RRMS patients over six months. It uses electrophysiological techniques and MRI while participants continue their standard MS treatments. Women can't join other drug studies during this time.

Participant Groups

Group I: Group B Experimental Treatment 1 Intervention

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

Group II: Group A Experimental Treatment 1 Intervention

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

Bazedoxifene Acetate is already approved in European Union, United States for the following indications:

Approved in European Union as Conbriza for:

• Postmenopausal osteoporosis

Approved in United States as Viviant for:

• Postmenopausal osteoporosis

Who Is Running the Clinical Trial?

Riley Bove, MD

Lead Sponsor

Trials

2

Recruited

100+

Findings from Research

Bazedoxifene (BZA) shows promising remyelinating effects in pre-clinical models and is being tested in a Phase 2 clinical trial involving female patients with relapsing-remitting multiple sclerosis, focusing on changes in Myelin Water Fraction (MWF) as the primary outcome.

The trial will also assess safety and tolerability, alongside secondary outcomes like visual evoked potential and cognitive measures, to evaluate BZA's potential as a treatment for myelin repair in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Nylander, A., Anderson, A., Rowles, W., et al.[2023]

Bazedoxifene acetate is an investigational oral drug that effectively prevents bone loss and reduces vertebral fracture risk in postmenopausal women, without affecting the endometrium or breast tissue.

When combined with conjugated estrogens, bazedoxifene shows promise in improving menopausal symptoms while providing skeletal benefits, making it a potential treatment for postmenopausal osteoporosis and related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. Lewiecki, EM.[2019]

Bazedoxifene acetate (BZA) demonstrated neuroprotective effects by reducing inflammation and promoting remyelination in a rat model of spinal cord injury, showing potential for therapeutic use.

In vivo studies indicated that BZA improved locomotor recovery and reduced markers of inflammation and cell death, suggesting it could enhance recovery after spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene, a Selective Estrogen Receptor Modulator, Promotes Functional Recovery in a Spinal Cord Injury Rat Model. Kim, Y., Roh, EJ., Joshi, HP., et al.[2021]

Bazedoxifene acetate is an effective oral treatment for preventing and treating osteoporosis in postmenopausal women, showing positive effects on bone health without stimulating breast or uterine tissue.

In combination with conjugated estrogens, bazedoxifene improves bone mineral density and reduces fracture risk while also alleviating menopausal symptoms, making it a promising option for women at high risk of osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. Kung, AW., Chu, EY., Xu, L.[2012]

Bazedoxifene is an effective treatment for postmenopausal osteoporosis, significantly reducing the incidence of new vertebral fractures over a 3-year trial, and continues to provide protection for up to 5 years in patients who remain on the medication.

It has a favorable safety profile, showing no significant stimulation of the endometrium or breast tissue, making it a suitable option for patients, particularly those at high risk for fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene: a review of its use in the treatment of postmenopausal osteoporosis. Duggan, ST., McKeage, K.[2021]

In a 2-year study involving 96 patients with relapsing-remitting multiple sclerosis, IFNbeta-1a significantly reduced the rate of exacerbations, with 53% of patients remaining exacerbation-free in Year 1 and 33% in Year 2.

The treatment was well tolerated, and while there were some improvements in disability scores (EDSS), the overall change was not statistically significant, indicating that while IFNbeta-1a is effective in reducing exacerbations, its impact on disability progression may vary among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefits of interferon beta-1a in relapsing-remitting MS: a phase IV study. Fernández, O., Arbizu, T., Izquierdo, G., et al.[2019]

In a study of 84 patients with relapsing remitting multiple sclerosis, CinnoVex demonstrated a significant decrease in gadolinium-enhancing lesions after 12 months, suggesting it may be more effective in reducing active disease compared to Avonex.

Both treatments showed similar safety profiles, with no significant differences in side effects or the development of neutralizing antibodies, indicating that CinnoVex is a safe alternative to Avonex for managing multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing efficacy and side effects of a weekly intramuscular biogeneric/biosimilar interferon beta-1a with Avonex in relapsing remitting multiple sclerosis: a double blind randomized clinical trial. Nafissi, S., Azimi, A., Amini-Harandi, A., et al.[2015]

In a study of 1282 multiple sclerosis patients, those treated with glatiramer acetate (GA) experienced a significantly lower risk of relapse (5.18%) compared to those treated with interferon beta-1a (10.01%), indicating GA may be more effective in preventing relapses.

Patients using GA also incurred lower total medical costs over two years ($41,121) compared to those on interferon beta-1a ($44,201), suggesting that GA not only helps in managing MS but is also more cost-effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glatiramer acetate and interferon beta-1a for intramuscular administration: a study of outcomes among multiple sclerosis intent-to-treat and persistent-use cohorts. Castelli-Haley, J., Oleen-Burkey, MA., Lage, MJ., et al.[2015]

In a study of 126 patients with relapsing-remitting multiple sclerosis, treatment with interferon beta 1A (Avonex) significantly reduced the annual relapse rate from 1.47 to 0.38 over 24 months, indicating its efficacy in managing the disease.

While Avonex was generally safe with minimal side effects, patients with less severe neurological deficits (EDSS < 2.0) showed improvement in their condition, whereas those with more severe deficits experienced deterioration, highlighting the importance of early intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Open trial of the effectiveness of interferon beta 1a (Avonex) in multiple sclerosis. Clinical assessment using motor coordination tests]. Selmaj, K., Członkowska, A., Kwieciński, H., et al.[2015]

Glatiramer acetate (GA) is an FDA-approved disease-modifying treatment for relapsing forms of multiple sclerosis (MS), initially discovered in the 1960s as a protective agent in animal models of MS.

The introduction of generic versions of GA could significantly reduce treatment costs and improve access to effective therapies for MS patients, addressing the high costs associated with current disease-modifying treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two decades of glatiramer acetate: From initial discovery to the current development of generics. Weinstock-Guttman, B., Nair, KV., Glajch, JL., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Bazedoxifene, a Selective Estrogen Receptor Modulator, Promotes Functional Recovery in a Spinal Cord Injury Rat Model. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. [2012]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Bazedoxifene: a review of its use in the treatment of postmenopausal osteoporosis. [2021]

6. Denmark pubmed.ncbi.nlm.nih.gov

Clinical benefits of interferon beta-1a in relapsing-remitting MS: a phase IV study. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Comparing efficacy and side effects of a weekly intramuscular biogeneric/biosimilar interferon beta-1a with Avonex in relapsing remitting multiple sclerosis: a double blind randomized clinical trial. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Glatiramer acetate and interferon beta-1a for intramuscular administration: a study of outcomes among multiple sclerosis intent-to-treat and persistent-use cohorts. [2015]

9. Poland pubmed.ncbi.nlm.nih.gov

[Open trial of the effectiveness of interferon beta 1a (Avonex) in multiple sclerosis. Clinical assessment using motor coordination tests]. [2015]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Two decades of glatiramer acetate: From initial discovery to the current development of generics. [2018]