Sirolimus for Inclusion Body Myositis

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Sirolimus, a drug already used in organ transplants, can slow down or stabilize the progression of inclusion body myositis (IBM), a muscle-wasting disease. Sirolimus affects certain immune cells and promotes protein breakdown, which might help patients maintain independence. Participants will receive either Sirolimus or a placebo (a non-active substance) to compare effectiveness. Potential candidates for this trial include those diagnosed with IBM who can walk at least 200 meters, using aids if needed, and have noticed their disease worsening over the past year. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sirolimus, also known as Rapamycin, has been studied for its safety in treating various conditions. It is already used in organ transplants to help prevent organ rejection. For inclusion body myositis (IBM), studies have tested sirolimus at a dose of 2 mg per day.

In earlier trials, most patients tolerated sirolimus well. The data indicated that severe side effects were uncommon. However, some participants experienced mild to moderate issues, such as mouth sores, diarrhea, and higher cholesterol levels. These side effects are similar to those observed when sirolimus is used for other conditions.

Sirolimus is currently being tested in a phase 3 trial for IBM. This phase indicates that the treatment has already undergone earlier studies to assess its safety. The trial aims to confirm sirolimus's tolerability and effectiveness for IBM. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Inclusion Body Myositis?

Most treatments for Inclusion Body Myositis (IBM) are limited in effectiveness and primarily focus on managing symptoms rather than altering the disease course. Sirolimus is unique because it works by inhibiting a specific pathway called mTOR, which plays a role in cell growth and immune response. Researchers are excited about Sirolimus because it targets the underlying mechanisms of IBM, potentially offering a more effective approach to slow disease progression, unlike current options that mainly provide symptomatic relief.

What evidence suggests that Sirolimus might be an effective treatment for Inclusion Body Myositis?

Research has shown that Sirolimus, also known as Rapamycin, might help people with Inclusion Body Myositis (IBM) by slowing or stabilizing the disease. In this trial, participants will receive either Sirolimus or a placebo. Earlier studies found that patients taking Sirolimus experienced a smaller decline in their ability to walk for 6 minutes compared to those on a placebo. This suggests that Sirolimus could help maintain muscle function longer. However, some studies did not find a significant improvement in muscle strength. Sirolimus affects certain immune cells and helps break down proteins, which might benefit those with IBM. ^{1 2 3 6 7}

Who Is on the Research Team?

Mazen Dimachkie

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. institut-myologie.org institut-myologie.org/en/2024/06/10/inclusion-myositis-and-sirolimus-the-final-results-of-the-rapami-trial-pave-the-way-for-a-phase-iii-2/

Inclusion myositis and sirolimus: the final results of ... Its aim was to evaluate the efficacy, safety and tolerability of sirolimus or rapamycin (Rapamune®) at a dose of 2 mg/day versus placebo for one year in 44 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11154752/

Effect of sirolimus on muscle in inclusion body myositis ... However, secondary outcome measures in the same study revealed significant differences, including a smaller decline in 6‐min walking distance (6MWD) and a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04789070

NCT04789070 | Phase III Trial of Sirolimus in IBM As Sirolimus, which acts to deplete effector T cells but preserving the Treg cells, was effective in this mouse model of myositis, it was therefore postulated ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38273639/

Sirolimus for treatment of patients with inclusion body ... We found no evidence for efficacy of sirolimus for treating inclusion body myositis based on maximal voluntary isometric knee extension strength and other ...

5. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620001226998

Sirolimus in Inclusion Body Myositis (IBM) This is an international, investigator-led Phase III trial of Sirolimus in 140 IBM patients. ... Individual participant data that underlie the results reported in ...

6. rmdopen.bmj.com rmdopen.bmj.com/content/rmdopen/11/1/e005176.full.pdf

Efficacy and safety of pharmacological treatments in ... ABSTRACT. Objective To identify the best evidence on the efficacy of treatment interventions for inclusion body myositis (IBM).

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40018746/

Optimism in inclusion body myositis This RCT aims to assess the efficacy of sirolimus compared to placebo in slowing or stabilising IBM progression, as measured by the mean change in patient ...