Sirolimus for Inclusion Body Myositis

Recruiting at 8 trial locations

Overseen By Mazen Dimachkie, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Kansas Medical Center

Must not be taking: Immunosuppressants, Immunomodulators, CYP3A4 inhibitors, others

Disqualifiers: Respiratory insufficiency, Kidney disease, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 84 weeks

140 Participants Needed

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking any immunosuppressive or immunomodulatory medications, as well as certain other medications that affect the metabolism of Sirolimus, before participating. If you're on any of these, you may need to stop them for a specific period before joining the trial.

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 data supports the effectiveness of the drug Sirolimus for treating inclusion body myositis?

A study showed that Sirolimus, which is a drug that affects certain cell growth pathways, led to quick and lasting improvement in muscle problems for a patient with inclusion body myositis. ^{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 sirolimus safe for humans?

Sirolimus, also known as Rapamune, has been used in various studies and is generally considered safe for humans, although it may have side effects like any medication. In a study on mice with muscle inflammation, sirolimus showed better immune suppression compared to another treatment, indicating its potential safety and effectiveness in managing inflammation. ^{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}

How does the drug sirolimus differ from other treatments for inclusion body myositis?

Sirolimus, also known as rapamycin, is unique because it targets the mammalian target of rapamycin (mTOR) pathway, which helps reduce inflammation and improve muscle function. Unlike other treatments that have failed to show significant benefits, sirolimus has shown promise in reducing inflammation and improving muscle strength in experimental models. ^{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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Sirolimus or placebo daily to assess its effect on disease progression in IBM

84 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Sirolimus

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+

The Perron Institute

Collaborator

Trials

1

Recruited

140+

Findings from Research

Sirolimus, taken at a dose of 2 mg/day, resulted in rapid and sustained improvement in motor symptoms for over a year in patients with inclusion body myositis (IBM), indicating its potential as an effective treatment.

The treatment was well tolerated with no adverse effects reported, although it did not significantly change CD8+ T-cell subsets, suggesting that sirolimus may work through mechanisms other than altering immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus leads to rapid and sustained clinical improvement of motor deficits in a patient with inclusion body myositis. Pawlitzki, M., Nelke, C., Korsen, M., et al.[2022]

Inclusion body myositis has a prevalence of 32 per million inhabitants, with significant differences between sexes: 19 per million women and 45 per million men, indicating a higher occurrence in men.

The disease is associated with a decreased survival rate, averaging 14 years from symptom onset, and shows notable sex differences in symptoms, such as dysphagia being more common in women (23%) compared to men (10%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidemiology, Survival, and Clinical Characteristics of Inclusion Body Myositis. Lindgren, U., Pullerits, R., Lindberg, C., et al.[2022]

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 pilot study involving 14 patients with sporadic inclusion-body myositis (s-IBM), oral simvastatin was found to be safe and well tolerated over a 12-month period, with no significant adverse effects reported.

Despite the safety of simvastatin, the study did not demonstrate any significant clinical improvement in s-IBM symptoms, indicating that it may not be an effective treatment for this condition at this time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot trial of simvastatin in the treatment of sporadic inclusion-body myositis. Sancricca, C., Mora, M., Ricci, E., et al.[2021]

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]