Vamorolone for Becker Muscular Dystrophy

Recruiting at 1 trial location

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

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This Phase II pilot study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, PD, and exploratory clinical efficacy of vamorolone 500mg (250mg for body weight \<50 kg) daily administered orally compared to placebo over a treatment period of 24 weeks in males with BMD. Funding Source - FDA OOPD

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.

What safety data is available for Vamorolone in treating Becker Muscular Dystrophy?

Vamorolone has been shown to have improved safety compared to prednisolone, avoiding or reducing key side effects related to behavior and growth. It has been tested in the bmx mouse model of Becker Muscular Dystrophy, where it demonstrated efficacy and safety. Additionally, in clinical trials for Duchenne Muscular Dystrophy, vamorolone showed no significant relationship between QTcF interval changes and maximum plasma concentration, indicating a favorable safety profile. Vamorolone targets dual nuclear receptors to treat inflammation and cardiomyopathy with improved safety over traditional corticosteroids like prednisone. ^{1 2 3 4 5}

Is Vamorolone safe for humans?

Vamorolone has been shown to have improved safety compared to other similar drugs like prednisolone, with fewer side effects related to behavior and growth in studies involving muscular dystrophy. It is designed to reduce inflammation with fewer negative effects, making it a potentially safer option for treating conditions like Duchenne and Becker muscular dystrophy. ^{1 2 3 4 5}

Is the drug Vamorolone a promising treatment for Becker Muscular Dystrophy?

Yes, Vamorolone is a promising drug for Becker Muscular Dystrophy. It has shown potential in improving muscle strength and increasing dystrophin protein, which is important for muscle health. It also appears to be safer than other similar drugs, making it a strong candidate for further study. ^{1 2 3 4 6}

How is the drug vamorolone unique for treating Becker muscular dystrophy?

Vamorolone is unique because it is a first-in-class dissociative steroidal anti-inflammatory drug that not only reduces inflammation but also increases dystrophin protein levels, which is crucial for muscle function. Unlike other treatments, it shows improved safety by reducing side effects commonly associated with traditional steroids. ^{1 2 3 4 6}

What data supports the idea that Vamorolone for Becker Muscular Dystrophy is an effective drug?

The available research shows that Vamorolone improves muscle strength and endurance in a mouse model of Becker Muscular Dystrophy. It increases the amount of dystrophin protein, which is important for muscle function, and has fewer side effects compared to another drug, prednisolone. This suggests that Vamorolone could be an effective treatment for Becker Muscular Dystrophy. ^{1 2 3 4 7}

What data supports the effectiveness of the drug Vamorolone for Becker Muscular Dystrophy?

Research shows that Vamorolone, a drug initially developed for Duchenne muscular dystrophy, improved muscle strength and increased dystrophin protein in a mouse model of Becker muscular dystrophy. This suggests it may help treat Becker muscular dystrophy by reducing inflammation and increasing dystrophin, a protein important for muscle health. ^{1 2 3 4 7}

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.

Clinical laboratory test results are within the normal range at the Screening Visit or not clinically significant in the opinion of the Investigator

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 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]

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]

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]

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, 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]

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]

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]

Citations

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

Vamorolone improves Becker muscular dystrophy and increases dystrophin protein in bmx model mice. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Exposure-Response Analysis of Vamorolone (VBP15) in Boys With Duchenne Muscular Dystrophy. [2021]

4. United States 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. [2020]

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

Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. [2021]

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

Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis. [2023]