Pozelimab + Cemdisiran for Inclusion Body Myositis

Overseen By Yessar Hussain, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Austin Neuromuscular Center

Must not be taking: Complement inhibitors

Disqualifiers: Other neurological, active malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

10 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had previous treatment with a complement inhibitor or be participating in another clinical trial. It's best to discuss your current medications with the trial team.

What data supports the idea that Pozelimab + Cemdisiran for Inclusion Body Myositis is an effective treatment?

The available research does not provide specific data on the effectiveness of Pozelimab + Cemdisiran for Inclusion Body Myositis. Instead, it discusses other treatments like bimagrumab and alemtuzumab. Bimagrumab showed some increase in muscle mass but no significant improvement in walking distance. Alemtuzumab showed a slight reduction in muscle strength decline. Overall, the research suggests that while some treatments may slow progression, there is no strong evidence of significant improvement in muscle function for Inclusion Body Myositis. ^{1 2 3 4 5}

What safety data is available for Pozelimab + Cemdisiran in treating Inclusion Body Myositis?

The provided research does not contain specific safety data for Pozelimab + Cemdisiran (also known as Poze-Cemdi) in the treatment of Inclusion Body Myositis. The studies mentioned focus on other treatments such as bimagrumab and alemtuzumab. Therefore, no existing safety data for Pozelimab + Cemdisiran can be extracted from these sources. ^{1 2 3 6 7}

Is Pozelimab/Cemdisiran a promising drug for inclusion body myositis?

Pozelimab/Cemdisiran could be promising because there are currently no effective drugs for inclusion body myositis, and new treatments are needed to address both the inflammation and muscle degeneration caused by the disease. ^{1 2 4 8 9}

What is the purpose of this trial?

To evaluate the efficacy of Pozelimab/Cemdisiran combination therapy in patients with sIBM

Research Team

Yessar M Hussain, M.D.

Principal Investigator

Austin Neuromuscular Center

Eligibility Criteria

This trial is for patients with sporadic Inclusion Body Myositis (sIBM), a muscle disease causing weakness and inflammation. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study or pose additional risks.

Inclusion Criteria

Willing and able to comply with clinic visits and study-related procedures

Provide informed consent signed by the study patient or legally acceptable representative

Able to understand and complete study-related questionnaires

Exclusion Criteria

I have a condition affecting my movement.

I haven't had meningococcal or pneumococcal vaccines in the last 5 years.

Known contraindication to meningococcal and pneumococcal vaccines

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pozelimab 200mg/Cemdisiran 200 mg SC injections every 4 weeks for 104 weeks. Injections are initially administered by study staff, with subsequent injections potentially administered at home by the patient or caregiver after training.

104 weeks

In-person visit for initial injection, subsequent visits as needed for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pozelimab/Cemdisiran

Trial Overview The trial is testing the effectiveness of combining two drugs, Pozelimab and Cemdisiran, in treating sIBM. The goal is to see if this combination therapy can improve symptoms or halt progression of the disease.

Participant Groups

Group I: INJECTION Experimental Treatment 1 Intervention

patients to receive Pozelimab 200mg/Cemdisiran 200 mg SC injections every 4 weeks for 104 weeks. SC injections will be administered by the study staff and the patient will be monitored for 30 minutes after the initial first injection. During the remainder of the study, injections can be administered at home by the patient or caregiver after injection training provided by the study staff. Designated persons will be observed to confirm their ability to perform the injections. The dosing window of the study treatment is within ±7 days from the scheduled dose date.

Who Is Running the Clinical Trial?

Austin Neuromuscular Center

Lead Sponsor

Trials

2

Recruited

20+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

In a large study involving 251 participants with inclusion body myositis, bimagrumab demonstrated a good safety profile, with no significant adverse cardiac effects and a similar rate of adverse events compared to placebo.

However, bimagrumab did not show any improvement in the primary outcome measure, the 6-minute walking distance, indicating that while it is safe, it may not be effective in enhancing mobility in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial. Hanna, MG., Badrising, UA., Benveniste, O., et al.[2020]

In a 2-year study involving 10 adults with sporadic inclusion body myositis (sIBM), bimagrumab was found to have a good safety profile, with common side effects including muscle spasms and falls, but none were directly related to the treatment.

While there was a modest increase in muscle mass (thigh muscle volume and lean body mass), the treatment did not result in significant clinical improvements in functional measures like walking distance or strength.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis. Sivakumar, K., Cochrane, TI., Sloth, B., et al.[2020]

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]

Inclusion body myositis is often misdiagnosed, with an average delay of 37 months from symptom onset to accurate diagnosis, affecting 40% of patients initially.

While significant clinical improvement with treatment is rare, therapy may slow disease progression, particularly with low-dose methotrexate and prednisone, as seen in some patients who experienced delayed progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inclusion body myositis: analysis of 32 cases. Sayers, ME., Chou, SM., Calabrese, LH.[2013]

In a study involving 251 patients, BYM338 (bimagrumab) did not significantly improve motor function, as measured by the 6-minute walking distance, compared to placebo after 52 weeks of treatment.

However, all BYM338 dose groups showed a dose-dependent increase in lean body mass, indicating a potential benefit in skeletal muscle mass despite the lack of improvement in motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Late phase II/III study of BYM338 in patients with sporadic inclusion body myositis (RESILIENT): Japanese cohort data]. Mori-Yoshimura, M., Yamashita, S., Suzuki, N., et al.[2022]

In a study involving 51 patients with inclusion body myositis (IBM) and 19 healthy donors, researchers found an expansion of KLRG1+ T cells, particularly in the effector memory re-expressing CD45RA (TemRA) and effector memory T cell (Tem) compartments, indicating a potential target for therapy.

The study revealed that KLRG1 expression in CD8+ T cells increased with differentiation, suggesting that targeting these highly differentiated T cells could be a promising approach in treating IBM, while NK cell populations remained unchanged between patients and healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells. Goyal, NA., Coulis, G., Duarte, J., et al.[2023]

In a study of patients with inclusion body myositis (IBM) treated with alemtuzumab, there were no significant changes in key inflammatory and degeneration markers, indicating limited efficacy of the treatment overall.

Some patients did experience a transient improvement in muscle strength, which correlated with reduced expression of certain inflammatory markers, suggesting that while alemtuzumab may not broadly affect inflammation, it could have benefits for a subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular treatment effects of alemtuzumab in skeletal muscles of patients with IBM. Schmidt, K., Kleinschnitz, K., Rakocevic, G., et al.[2018]

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]

Sporadic inclusion body myositis (IBM) is a slowly progressive disease that typically leads to wheelchair use 12-20 years after symptoms begin, but it does not significantly affect life expectancy.

Recent advancements include new diagnostic criteria with high sensitivity and specificity, as well as potential treatments like follistatin and bimagrumab, which target specific aspects of the disease's pathophysiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inclusion body myositis: update. Lahouti, AH., Amato, AA., Christopher-Stine, L.[2014]

References

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

Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial. [2020]

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

Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis. [2020]

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

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

4. Canada pubmed.ncbi.nlm.nih.gov

Inclusion body myositis: analysis of 32 cases. [2013]

5. Japan pubmed.ncbi.nlm.nih.gov

[Late phase II/III study of BYM338 in patients with sporadic inclusion body myositis (RESILIENT): Japanese cohort data]. [2022]

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

Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Molecular treatment effects of alemtuzumab in skeletal muscles of patients with IBM. [2018]

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

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

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

Inclusion body myositis: update. [2014]