Vamorolone for Becker Muscular Dystrophy

No longer recruiting at 2 trial locations

Overseen By Eric P Hoffman, Ph.D.

Age: 18 - 65

Sex: Male

Trial Phase: Phase 2

Sponsor: ReveraGen BioPharma, Inc.

Must not be taking: Mineralocorticoids, Herbal supplements

Disqualifiers: Renal impairment, Hepatic impairment, Diabetes, others

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

Compensation: Varies

Number of Visits: 55

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called vamorolone for Becker Muscular Dystrophy (BMD), a condition that weakens muscles over time. The study aims to determine the safety and effectiveness of vamorolone by comparing it to a placebo (a harmless pill with no medicine). Men diagnosed with BMD who can run or walk 10 meters in 30 seconds or less might be suitable for this trial. Participants will take either vamorolone or a placebo for 24 weeks. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

Yes, you need to stop taking oral glucocorticoids or other oral immunosuppressive agents at least 3 months before starting the study medication. Inhaled or topical glucocorticoids are allowed if used at a stable dose for at least 4 weeks before starting the study. You also need to stop taking certain herbal remedies and supplements that affect muscle strength and function at least 4 weeks before starting the study.

Will I have to stop taking my current medications?

The trial requires that you have not taken oral glucocorticoids or other oral immunosuppressive agents for at least 3 months before starting the study medication. Additionally, you should not have used certain mineralocorticoid receptor agents or herbal remedies that affect muscle strength within 4 weeks before starting the study.

Is there any evidence suggesting that vamorolone is likely to be safe for humans?

Research shows that vamorolone is generally safe for use. Studies have found it to be safer than prednisolone, a similar drug. Vamorolone often avoids or reduces side effects, particularly those affecting behavior and growth, which means patients might experience fewer problems. Additionally, tests on people with Duchenne muscular dystrophy showed positive effects on muscle function without major safety issues. While this evidence is promising, each person's experience can differ. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Becker Muscular Dystrophy?

Unlike the standard corticosteroid treatments for Becker Muscular Dystrophy, such as prednisone and deflazacort, Vamorolone is unique because it offers a potentially safer alternative with fewer side effects. Most corticosteroids work by broadly suppressing the immune system, which can lead to unwanted effects like weight gain and bone thinning. Vamorolone, however, is designed to retain anti-inflammatory benefits while minimizing these adverse effects, thanks to its novel mechanism of action. Researchers are excited because Vamorolone may provide similar or improved muscle function benefits without the same level of complications, offering a better quality of life for patients.

What evidence suggests that vamorolone might be an effective treatment for Becker Muscular Dystrophy?

Research has shown that vamorolone, which participants in this trial may receive, might help treat Becker Muscular Dystrophy (BMD) by reducing muscle inflammation. Studies have found that it can safely lower inflammation, improving muscle function. Vamorolone also uniquely increases dystrophin protein levels, crucial for muscle strength and repair. People with muscular dystrophy who have used vamorolone demonstrated better muscle function. This suggests that vamorolone could offer real benefits for those with BMD. ^{1 2 3 4 6}

Who Is on the Research Team?

Paula Clemens, M.D.

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for males with Becker Muscular Dystrophy who can walk 10 meters in ≤ 30 seconds, even with a cane or walker. They should have an NSAA score ≤ 32 and not be on oral steroids or immunosuppressants for the past 3 months. Participants must agree to use barrier contraception during the study and be between 18-65 years old.

Inclusion Criteria

Subject agrees to use barrier contraception methods during participation in the study and for 30 days after the tapering dose is completed

My NSAA score is 32 or lower.

I can walk or run 10 meters in 30 seconds or less, even with help from devices.

Exclusion Criteria

I have not taken any experimental drugs in the last 3 months.

I have not received a live vaccine in the last 14 days.

I have heart muscle disease with symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 5 weeks

Baseline

Baseline assessments are conducted prior to the first administration of study medication

1 day

Treatment

Participants receive vamorolone or placebo for 24 weeks with assessments at Week 4, Week 12, and Week 24

24 weeks

Visits at Day 1, Week 4, Week 12, and Week 24

Dose-tapering

Participants not continuing with further vamorolone treatment undergo a 4-week dose-tapering period

4 weeks

Contact at Week 26

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Visit at Week 28

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Vamorolone

Trial Overview The study tests Vamorolone, a potential treatment for BMD, against a placebo over six months. It's double-blind, meaning neither researchers nor participants know who gets the real drug versus placebo. The goal is to assess safety, how well it works (efficacy), and its effects on the body (pharmacodynamics).

How Is the Trial Designed?

Group I: Vamorolone 500mg/day [250mg if <50kg body weight] Experimental Treatment 1 Intervention

Subjects will be randomized to one of two treatment groups in a 1:2 ratio (placebo:vamorolone).

Group II: Placebo Placebo Group 1 Intervention

Subjects will be randomized to one of two treatment groups in a 1:2 ratio (placebo:vamorolone).

Who Is Running the Clinical Trial?

ReveraGen BioPharma, Inc.

Lead Sponsor

Trials

9

Recruited

440+

Santhera Pharmaceuticals

Industry Sponsor

Trials

32

Recruited

2,800+

Published Research Related to This Trial

Vamorolone, a new steroidal anti-inflammatory drug, was found to be safe and well tolerated in a 24-week study involving 48 boys with Duchenne muscular dystrophy (DMD), with no major adverse effects typically associated with glucocorticoids.

The 2.0 mg/kg/day dose of vamorolone improved muscle function, specifically the time to stand from a supine position, suggesting its efficacy in enhancing mobility in boys with DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Hoffman, EP., Schwartz, BD., Mengle-Gaw, LJ., et al.[2021]

In a clinical trial involving boys with Duchenne muscular dystrophy, vamorolone demonstrated significant improvements in clinical outcomes after 24 weeks of daily dosing, particularly in the time to stand from supine, which was the most sensitive measure of efficacy.

The study found that typical exposure to vamorolone at a daily dose of 2 mg/kg led to substantial decreases in proinflammatory biomarkers within just 2 weeks, indicating its potential anti-inflammatory effects without significant impact on heart rhythm as measured by QTcF intervals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-Response Analysis of Vamorolone (VBP15) in Boys With Duchenne Muscular Dystrophy. Li, X., Conklin, LS., van den Anker, J., et al.[2021]

Vamorolone, a first-in-class drug, acts as an antagonist for the mineralocorticoid receptor (MR) and a dissociative ligand for the glucocorticoid receptor (GR), showing improved safety and efficacy in treating inflammation and cardiomyopathy in Duchenne muscular dystrophy compared to traditional treatments like prednisone.

In a mouse model of Duchenne muscular dystrophy, vamorolone effectively prevents MR-mediated cardiomyopathy and associated negative effects, while prednisolone exacerbates these conditions, highlighting vamorolone's potential as a safer therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Heier, CR., Yu, Q., Fiorillo, AA., et al.[2020]

In a study involving 23 boys with Duchenne muscular dystrophy (DMD) over 18 months, vamorolone treatment led to significant improvements in motor functions compared to corticosteroid-naïve individuals, showing similar efficacy to traditional corticosteroids without the associated growth stunting.

Vamorolone was associated with fewer adverse effects, such as weight gain and behavioral changes, compared to standard corticosteroids like prednisone and deflazacort, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open-label extension study. Smith, EC., Conklin, LS., Hoffman, EP., et al.[2020]

Vamorolone significantly improved mobility in Duchenne muscular dystrophy (DMD) patients, showing better results in standing, walking, and climbing compared to placebo, based on a meta-analysis of 4 studies with 277 participants.

When compared to glucocorticoids, vamorolone also demonstrated advantages in walking velocity and height percentile for age, suggesting it may be a more effective treatment option for DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis. Elhalag, RH., Motawea, KR., Talat, NE., et al.[2023]

Vamorolone, a new anti-inflammatory drug, was found to be safe and well-tolerated in a 2-week study involving 48 boys aged 4 to 7 with Duchenne muscular dystrophy, even at the highest dose of 6.0 mg/kg/day.

The study showed that vamorolone has a better safety profile compared to traditional glucocorticoids, with reduced insulin resistance and adrenal suppression, while still demonstrating anti-inflammatory effects and improving muscle membrane stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug. Conklin, LS., Damsker, JM., Hoffman, EP., et al.[2022]

Vamorolone, a novel corticosteroid, shows promise in treating Becker muscular dystrophy (BMD) by improving muscle strength and reducing inflammation in a mouse model, indicating its potential efficacy for this genetic condition.

Compared to prednisolone, vamorolone has a better safety profile, causing fewer side effects related to behavior and growth, while also increasing dystrophin protein levels in both heart and skeletal muscle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vamorolone improves Becker muscular dystrophy and increases dystrophin protein in bmx model mice. McCormack, NM., Nguyen, NY., Tully, CB., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05166109

NCT05166109 | A Study to Assess Vamorolone in Becker ... This Phase II pilot study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, PD, and exploratory clinical ...

2. parentprojectmd.org parentprojectmd.org/clinical-trial/a-study-to-assess-vamorolone-in-becker-muscular-dystrophy-bmd/

A Study to Assess Vamorolone in Becker Muscular ... This Phase II pilot study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, PD, and exploratory clinical ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10391915/

Vamorolone improves Becker muscular dystrophy and ... We hypothesize vamorolone can treat BMD by safely reducing inflammatory signaling in muscle and through a novel mechanism of increasing dystrophin protein.

4. clinicaltrial.be clinicaltrial.be/en/details/35328?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

A Study to Assess Vamorolone in Becker Muscular ... This Phase II pilot study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, PD, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10657680/

Considering the Promise of Vamorolone for Treating ... This commentary provides an independent consideration of data related to the drug vamorolone (VBP15) as an alternative steroid proposed for ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2788382

Efficacy and Safety of Vamorolone in Duchenne Muscular ... Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function.  Neurology. 2019;93(13):e1312-e1323. doi ...