Weekly Prednisolone for Duchenne Muscular Dystrophy

Recruiting at 4 trial locations

Overseen By Sara Marshall

Age: < 18

Sex: Male

Trial Phase: Phase 4

Sponsor: Anne M. Connolly

Must not be taking: Glucocorticosteroids

Disqualifiers: None

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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a lower dose of the medication prednisolone (a corticosteroid) can be as effective as a higher dose in treating Duchenne muscular dystrophy (DMD). DMD causes muscle weakness and damage. In the trial, one group of participants takes prednisolone weekly. It targets young children, specifically those between 1 and 30 months old, who show signs of muscle weakness typical of DMD and have specific genetic markers. Participants must not have received previous treatment with similar medications. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have been treated with glucocorticosteroids before joining.

What is the safety track record for Prednisolone?

Research has shown that prednisolone, the treatment under study, has been used safely in other studies for Duchenne Muscular Dystrophy (DMD). A review of these studies found that prednisolone helped maintain motor improvements and led to better growth compared to prednisone, a similar drug, over 48 weeks. This suggests that prednisolone is well-tolerated and can be helpful for patients with DMD.

It is important to note that this trial is in a later phase, indicating that earlier research has already demonstrated the treatment's relative safety. While every treatment can have side effects, available evidence suggests that prednisolone is generally safe for treating DMD. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard of care for Duchenne Muscular Dystrophy, which typically involves daily corticosteroids like deflazacort or prednisone, this treatment uses a weekly dose of prednisolone. Researchers are excited about this approach because it could potentially reduce the side effects associated with daily steroid use, such as weight gain and bone thinning, while still maintaining muscle strength. By administering prednisolone weekly, patients might experience a better quality of life with fewer interruptions from side effects.

What evidence suggests that this treatment might be an effective treatment for Duchenne Muscular Dystrophy?

Research has shown that prednisolone effectively treats Duchenne Muscular Dystrophy (DMD). Studies have found that steroid therapy, including prednisolone, helps maintain muscle strength and prolongs the ability to walk in patients with DMD. An observational study found that 74% of boys with DMD used prednisolone, indicating its widespread effectiveness. Additionally, steroid treatments like prednisolone have been linked to better outcomes in managing DMD. This evidence supports the effectiveness of prednisolone in managing symptoms of Duchenne Muscular Dystrophy. ^{3 4 6 7 8}

Who Is on the Research Team?

Anne Connolly, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for young children from 1 month to 30 months old who show signs of Duchenne Muscular Dystrophy (DMD) on physical exams, have high levels of an enzyme called creatine kinase in their blood, and a genetic mutation known to cause DMD. Children previously treated with glucocorticosteroids can't participate.

Inclusion Criteria

I am between 1 month and 30 months old.

I have Duchenne muscular dystrophy with high creatine kinase levels and a confirmed genetic mutation.

Exclusion Criteria

I have been treated with steroids before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5mg/kg/week of prednisolone to assess efficacy and side effects

24 months

Regular visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Prednisolone

Trial Overview The study is testing if a lower weekly dose of the corticosteroid Prednisolone (5mg/kg) is as effective as the standard higher dose (10mg/kg) for treating symptoms of Duchenne Muscular Dystrophy in infants.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

This is a one-arm study and the group of subjects are all experimental and will receive drug.

Prednisolone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Prednisolone for:

• Asthma
• Rheumatoid arthritis
• Crohn's disease
• Ulcerative colitis
• Multiple sclerosis
• Polymyalgia rheumatica
• Giant cell arteritis

Approved in United States as Prednisolone for:

• Asthma
• Rheumatoid arthritis
• Crohn's disease
• Ulcerative colitis
• Multiple sclerosis
• Polymyalgia rheumatica
• Giant cell arteritis

Approved in Canada as Prednisolone for:

• Asthma
• Rheumatoid arthritis
• Crohn's disease
• Ulcerative colitis
• Multiple sclerosis
• Polymyalgia rheumatica
• Giant cell arteritis

Approved in Japan as Prednisolone for:

• Asthma
• Rheumatoid arthritis
• Crohn's disease
• Ulcerative colitis
• Multiple sclerosis
• Polymyalgia rheumatica
• Giant cell arteritis

Who Is Running the Clinical Trial?

Anne M. Connolly

Lead Sponsor

Trials

1

Recruited

30+

Muscular Dystrophy Association

Collaborator

Trials

38

Recruited

60,800+

University of Texas

Collaborator

Trials

193

Recruited

143,000+

Virginia Commonwealth University

Collaborator

Trials

732

Recruited

22,900,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborator

Trials

275

Recruited

5,182,000+

Published Research Related to This Trial

A 5-year follow-up of two boys with Duchenne muscular dystrophy showed a remarkable response to a low-dosage, intermittent regimen of prednisolone, with one boy achieving complete remission of symptoms and the other maintaining significant improvement for nearly 5 years.

The treatment was well tolerated, with no signs of chronic prednisolone toxicity or bone demineralization, suggesting that this approach could be safe for long-term use in young children with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Dubowitz, V., Kinali, M., Main, M., et al.[2019]

Deflazacort has been shown to significantly benefit boys with Duchenne muscular dystrophy by prolonging ambulation, preserving cardiac and respiratory function, reducing scoliosis, and improving overall survival, based on long-term data from two Canadian centers.

While effective, common side effects of deflazacort treatment include weight gain, decreased height, and cataract formation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Canadian experience with long-term deflazacort treatment in Duchenne muscular dystrophy. McAdam, LC., Mayo, AL., Alman, BA., et al.[2021]

A special program involving low-dose prednisolone (0.5 mg/kg per day, effectively 0.25 mg/kg daily due to alternate day dosing) was tested in a randomized double-blind trial with 50 patients suffering from Duchenne-Becker muscular dystrophy.

Preliminary results indicate beneficial effects from the treatment without significant side effects, suggesting that this low-dose regimen may be a safe and effective option for managing the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of low doses of prednisolone for the treatment of patients with Duchenne-Becker myodystrophy]. Shakhovskaia, NI., Shishkin, SS., Skozobtseva, LF., et al.[2016]

In a 12-month study involving 41 boys with Duchenne or Becker muscular dystrophy, treatment with prednisolone significantly improved muscle force and function or slowed muscle deterioration.

The study confirmed previous findings that prednisolone is effective in managing symptoms of muscular dystrophy, although one participant experienced excessive weight gain as a side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose prednisolone treatment in Duchenne and Becker muscular dystrophy. Bäckman, E., Henriksson, KG.[2019]

A 20-year-old patient with Duchenne muscular dystrophy, treated with intermittent pulse prednisone from ages 3 to 17 for severe asthma, showed remarkable preservation of skeletal muscle function compared to his untreated uncle who died at 19.

This case suggests that long-term pulse prednisone therapy may provide significant clinical benefits in managing Duchenne muscular dystrophy, warranting further research into its efficacy and safety for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preserving function in Duchenne dystrophy with long-term pulse prednisone therapy. Carter, GT., McDonald, CM.[2019]

Prednisone and deflazacort are currently the most promising corticosteroids for providing temporary functional improvement in boys with Duchenne muscular dystrophy, a severe childhood condition that leads to loss of mobility and early death.

While there is no definitive cure for Duchenne muscular dystrophy yet, using these corticosteroids along with careful dietary management and monitoring for side effects is recommended as the best interim treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Wong, BL., Christopher, C.[2017]

In a double-blind trial involving 28 patients with Duchenne muscular dystrophy, Deflazacort (DF) showed statistically significant improvements in muscle strength and function compared to a placebo, indicating its efficacy as a treatment option.

While some mild side effects were observed, such as increased appetite and a cushingoid appearance in a few patients, no one had to stop taking the medication, suggesting that DF may have a better safety profile than traditional steroids like prednisone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroids in Duchenne muscular dystrophy--deflazacort trial. Mesa, LE., Dubrovsky, AL., Corderi, J., et al.[2019]

In a meta-analysis of clinical trials involving patients with nonsense mutation Duchenne muscular dystrophy, deflazacort showed significant improvements in physical function compared to prednisone/prednisolone, particularly in the 6-minute walk distance (6MWD) with a mean difference of 39.54 meters.

Deflazacort also demonstrated clinically meaningful enhancements in timed function tests, such as the 4-stair climb and descend, indicating its effectiveness in delaying the loss of physical milestones over 48 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy. Shieh, PB., Elfring, G., Trifillis, P., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11981458/

Comparing intermittent and daily prednisone in duchenne ... Effect of different corticosteroid dosing regimens on clinical outcomes in boys with Duchenne muscular dystrophy: a randomized clinical trial.

2. vivli.org vivli.org/associations-between-steroid-treatment-functional-outcomes-and-disease-milestones-among-non-ambulatory-patients-with-duchenne-muscular-dystrophy-dmd/

Associations between steroid treatment, functional ... This study will examine the association between steroid treatment and selected functional outcomes, body weight, and disease milestones among relevant ...

3. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2795868

Efficacy and Safety of Vamorolone vs Placebo ... Efficacy and safety of vamorolone in Duchenne muscular dystrophy: a 30-month nonrandomized controlled open-label extension trial.

4. jnnp.bmj.com jnnp.bmj.com/content/96/8/794

Observational study of changes to glucocorticosteroid ... Results Data on GC usage were available for 1117 boys, across 6905 observations, with 74% of boys GC treated. Prednisolone was the most common regime in the ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0387760416300298

Long-term outcomes of steroid therapy for Duchenne ... Later clinical trials confirmed that steroid therapy effectively prolonged muscle strength and ambulation in DMD patients [4], and the utility of steroid ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12187702/

A Review and Meta-Analysis of Efficacy and Safety Similarly, Dang et al reported maintained motor improvements and better growth outcomes compared with prednisone over 48 weeks. These findings ...

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000208112

Efficacy and Safety of Vamorolone Over 48 Weeks in Boys ... This study provides Class I evidence that for boys with DMD, the efficacy of vamorolone at a dose of 6 mg/kg/d was maintained over 48 weeks.

8. biorxiv.org biorxiv.org/content/10.1101/2025.02.26.640472.full.pdf

Enhancement of Prednisolone efficacy and ... Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug. Pharmacol ...