Sirolimus for Inclusion Body Myositis

Recruiting at8 trial locations

Overseen by Mazen Dimachkie

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: University of Kansas Medical Center

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests Sirolimus, a drug used in organ transplants, on patients with Inclusion Body Myositis (IBM). IBM causes muscle weakness, and current treatments are often ineffective. Sirolimus may help by calming harmful immune responses and cleaning up damaged proteins in muscle cells. Sirolimus has been used in organ transplant recipients to reduce the risk of skin cancer and manage immune system activity.

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

Yes, you may need to stop certain medications. The trial excludes participants who have taken immunosuppressive or immunomodulatory medications recently, such as high-dose prednisolone, IVIG, methotrexate, mycophenolate, Sirolimus, Everolimus, calcineurin inhibitors, azathioprine, rituximab, alemtuzumab, or other biologics. Additionally, medications affecting Sirolimus metabolism, like strong CYP3A4 inhibitors or inducers, are also restricted.

What data supports the idea that the drug Sirolimus for Inclusion Body Myositis is an effective treatment?

The available research shows that Sirolimus led to rapid and sustained improvement in motor deficits for a patient with Inclusion Body Myositis. This suggests that Sirolimus might be effective in improving muscle function in people with this condition. Compared to other treatments like Alemtuzumab and Simvastatin, which did not show significant improvement or were not recommended, Sirolimus appears to have a more positive impact on muscle strength and function. ^{1 2 3 4 5}

What safety data exists for Sirolimus in treating Inclusion Body Myositis?

The available research does not provide direct safety data for Sirolimus in treating Inclusion Body Myositis. However, a study on a murine model of experimental autoimmune myositis showed that Rapamycin (another name for Sirolimus) had better immune suppressive effects compared to methylprednisolone, with decreased inflammation and improved muscle strength. No specific safety concerns were mentioned in this study. Further clinical trials are needed to establish the safety profile of Sirolimus in human patients with Inclusion Body Myositis. ^{1 2 3 5 6}

Is the drug Sirolimus a promising treatment for Inclusion Body Myositis?

Yes, Sirolimus shows promise as a treatment for Inclusion Body Myositis. It has been reported to improve muscle function and reduce inflammation in both human and animal studies. This suggests it could help people with this muscle disease. ^{1 3 6 7 8}

Research Team

Mazen Dimachkie

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

Adults aged 45+ with Inclusion Body Myositis (IBM) who can walk at least 200m with or without aids and have shown disease progression in the past year. Participants must understand the study, consent to it, not have used Sirolimus recently, be HIV and hepatitis negative, not pregnant or planning pregnancy, and agree to use contraception.

Inclusion Criteria

Your condition has gotten worse in the past year, as confirmed by a neuromuscular specialist through various tests and examinations.

You are a man or woman who is 45 years old or older.

Adults able to read and understand the Participant Information Sheet, and who freely provide written Informed Consent for the study

Exclusion Criteria

You have taken Sirolimus or Everolimus in the last 6 months.

If patient has received a live vaccine within the last 12 weeks

Has taken any investigational study drug within 30 days or five half-lives of the prior agent (whichever is longer) prior to the Baseline visit

Treatment Details

Interventions

• Placebo (Drug)
• Sirolimus (mTOR inhibitor)

Trial Overview The trial is testing if Sirolimus can slow down IBM's progress compared to a placebo. It's based on earlier results suggesting benefits from Sirolimus due to its effects on immune cells and protein degradation. Patients will be randomly assigned either the drug or a placebo for comparison.

Participant Groups

Group I: Sirolimus Active Control 1 Intervention

2mg capsules once daily

Group II: Placebo Placebo Group 1 Intervention

2mg capsules once daily

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Dr. Steve Stites

University of Kansas Medical Center

Chief Executive Officer

MD from University of Kansas School of Medicine

Dr. Matthias Salathe

University of Kansas Medical Center

Chief Medical Officer

MD from University of Kansas School of Medicine

The Perron Institute

Collaborator

Trials

1

Recruited

140+

Findings from Research

Long-term treatment with bimagrumab for up to 2 years in patients with sporadic inclusion body myositis (sIBM) was found to be safe and well-tolerated, with a high incidence of treatment-emergent adverse events similar to the placebo group.

Despite its safety profile, bimagrumab did not demonstrate any significant clinical benefits in improving mobility, as indicated by the progressive deterioration in the 6-minute walk distance across all treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis: Long-term Extension of RESILIENT. Amato, AA., Hanna, MG., Machado, PM., et al.[2022]

A single series of Alemtuzumab infusions in 13 patients with sporadic inclusion-body myositis (sIBM) significantly slowed disease progression, with only a 1.9% decline in muscle strength over 6 months compared to a 14.9% decline in the natural history, indicating a potential therapeutic benefit.

The treatment led to a notable reduction in endomysial T cells and inflammatory markers in muscle biopsies, suggesting that Alemtuzumab not only depletes peripheral lymphocytes but also reduces inflammation associated with sIBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Dalakas, MC., Rakocevic, G., Schmidt, J., et al.[2022]

In a study comparing rapamycin and methylprednisolone (MP) in a mouse model of autoimmune myositis, rapamycin significantly reduced inflammation and improved muscle strength more effectively than MP over a 14-day treatment period.

The therapeutic effects of rapamycin were associated with increased plasma levels of transforming growth factor-β (TGF-β), suggesting that its immune-suppressive effects may be mediated through the TGF-β signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of rapamycin and methylprednisolone for treating inflammatory muscle disease in a murine model of experimental autoimmune myositis. Kang, J., Feng, D., Yang, F., et al.[2020]

Rapamycin effectively improved muscle strength and reduced inflammation in a mouse model of experimental autoimmune myositis, demonstrating its potential as both a preventive and curative treatment.

The treatment led to a decrease in effector T cells while increasing the frequency of activated regulatory T cells (Tregs), suggesting a mechanism where rapamycin modulates immune responses favorably in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial role of rapamycin in experimental autoimmune myositis. Prevel, N., Allenbach, Y., Klatzmann, D., et al.[2021]

Inclusion body myositis (IBM) is a slowly progressing inflammatory muscle disease primarily affecting older adults, characterized by T-cell mediated autoimmunity and muscle degeneration, with diagnosis typically confirmed through muscle biopsy.

Current treatments, including various immunosuppressants and intravenous immunoglobulin, have shown limited effectiveness, although a small study suggested that the T-cell depleting monoclonal antibody alemtuzumab may slow disease progression by reducing T-cell presence in muscle tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Inclusion body myositis--a rarely recognized disorder]. Dézsi, L., Danielsson, O., Gáti, I., et al.[2013]

References

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

Sirolimus leads to rapid and sustained clinical improvement of motor deficits in a patient with inclusion body myositis. [2022]

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

Epidemiology, Survival, and Clinical Characteristics of Inclusion Body Myositis. [2022]

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

Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis: Long-term Extension of RESILIENT. [2022]

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

Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

Pilot trial of simvastatin in the treatment of sporadic inclusion-body myositis. [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Comparison of rapamycin and methylprednisolone for treating inflammatory muscle disease in a murine model of experimental autoimmune myositis. [2020]

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

Beneficial role of rapamycin in experimental autoimmune myositis. [2021]

8. Hungary pubmed.ncbi.nlm.nih.gov

[Inclusion body myositis--a rarely recognized disorder]. [2013]