Canakinumab for Duchenne Muscular Dystrophy

Overseen By Christopher Spurney, MD

Age: Any Age

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Children's National Research Institute

Must not be taking: Glucocorticoids, Immunosuppressants

Disqualifiers: Renal impairment, Hepatic impairment, Diabetes, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 4

Duration: 1 day

3 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing canakinumab, a medication that reduces inflammation, in young boys with Duchenne Muscular Dystrophy (DMD) who have not been treated with steroids. The study aims to see if the medication is safe and effective by monitoring changes in blood markers over a short period. Canakinumab has been studied for various inflammatory conditions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking oral glucocorticoids or other immunosuppressive agents, you may not be eligible unless they were used for a different condition and stopped at least 3 months before the trial. Inhaled or topical glucocorticoids are allowed if the dose has been stable for at least 3 months.

How is the drug Canakinumab different from other treatments for Duchenne Muscular Dystrophy?

Canakinumab is unique because it is an anti-inflammatory drug that targets interleukin-1 beta, a protein involved in inflammation, which is different from other DMD treatments that focus on replacing or increasing dystrophin protein levels. ^{1 2 3 4 5}

What data supports the effectiveness of the drug canakinumab for treating Duchenne Muscular Dystrophy?

Canakinumab has shown effectiveness in treating other inflammatory conditions like cryopyrin-associated periodic syndromes (CAPS), where it provided rapid and sustained responses in most patients. This suggests it might help with inflammation-related aspects of Duchenne Muscular Dystrophy, although direct evidence for this specific condition is not available. ^{6 7 8 9 10}

Who Is on the Research Team?

Christopher Spurney

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

This trial is for young boys with Duchenne Muscular Dystrophy (DMD) who are between 2 to less than 6 years old, have not been treated with steroids, and can walk. They should have normal or acceptable lab test results and no major organ issues, diabetes, immunosuppression, recent infections or vaccinations. They must not be on other investigational drugs or have had certain treatments within the past 3 months.

Inclusion Criteria

I am at least 2 years old.

Your lab test results are mostly normal, and if not, they are not too far from normal. You also tested negative for tuberculosis.

I have been diagnosed with Duchenne Muscular Dystrophy (DMD).

Exclusion Criteria

I have used or am using oral steroids or other drugs that weaken my immune system.

I have or had a long-term fungal or viral infection.

Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive a single subcutaneous dose of canakinumab

1 day

1 visit (in-person)

Post-treatment Evaluation

Participants undergo safety and serum biomarker monitoring

30 days

2 visits (in-person), 1 phone assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab

Trial Overview The trial tests Canakinumab Injection [Ilaris], an antibody against interleukin-1 beta (IL1β), for safety and potential efficacy in reducing muscle inflammation in DMD patients. Participants will receive a single subcutaneous dose of Canakinumab and will be monitored over 30 days for changes in serum biomarkers related to inflammation.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Canakinumab treatment

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

Approved in European Union as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Approved in United States as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Foundation to Eradicate Duchenne

Collaborator

Trials

1

Recruited

3+

Published Research Related to This Trial

Canakinumab demonstrated long-term efficacy in treating active systemic juvenile idiopathic arthritis (JIA), with 62% of patients achieving a 50% improvement in disease activity after 2 years, and sustained efficacy observed for up to 5 years.

The treatment was associated with a significant reduction in glucocorticoid use, with 15.6% of patients discontinuing and 22% tapering their dosage, while no new safety concerns were identified during the long-term study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. Ruperto, N., Brunner, HI., Quartier, P., et al.[2019]

In a phase 2 trial involving 120 boys with Duchenne muscular dystrophy (DMD), domagrozumab was found to be generally safe and well tolerated, with most adverse events being mild and not related to the treatment.

However, the study did not show a significant treatment effect on functional measures, such as the 4-stair climb time, indicating that domagrozumab may not provide the expected benefits in improving muscle function in DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Wagner, KR., Abdel-Hamid, HZ., Mah, JK., et al.[2021]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency: results from the randomised Phase 3 CLUSTER trial. [2022]

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

Trial of canakinumab, an IL-1β receptor antagonist, in patients with inclusion body myositis. [2020]

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

Safety and tolerability of canakinumab, an IL-1β inhibitor, in type 2 diabetes mellitus patients: a pooled analysis of three randomised double-blind studies. [2022]

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

Canakinumab: in patients with cryopyrin-associated periodic syndromes. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Treatment with human immunoglobulin G improves the early disease course in a mouse model of Duchenne muscular dystrophy. [2016]

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

Casimersen: First Approval. [2021]

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

Monitoring duchenne muscular dystrophy gene therapy with epitope-specific monoclonal antibodies. [2012]

9. Germany pubmed.ncbi.nlm.nih.gov

Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. [2021]