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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, Pozelimab and Cemdisiran, to determine their effectiveness in helping people with sporadic Inclusion Body Myositis (sIBM), a muscle-wasting condition. The goal is to assess how well this new treatment manages sIBM symptoms. Participants will receive injections every four weeks for about two years, with study staff monitoring the first few injections. This trial may suit those diagnosed with sIBM who can walk at least 20 feet, even with a walking aid like a cane or walker. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of Pozelimab and Cemdisiran is generally safe in studies for other conditions. For instance, one study found that this treatment effectively managed symptoms and was safe for patients. In these studies, patients did not report any major safety issues. However, since this trial is in the early stages, the researchers are still collecting detailed safety information for its use in treating inclusion body myositis. Early-phase trials like this one primarily focus on ensuring the treatment's safety for people, so there is still much to learn. ^{1 2 3 4 5}

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

Unlike the standard treatments for inclusion body myositis, which often involve physical therapy and off-label use of immunosuppressants like corticosteroids and methotrexate, Pozelimab and Cemdisiran offer a novel approach. Researchers are excited about these treatments because they target specific components of the immune system. Pozelimab works by inhibiting the complement pathway, a part of the immune system that contributes to inflammation, while Cemdisiran reduces the production of a protein involved in this pathway. Additionally, these treatments are conveniently administered as subcutaneous injections, which can be done at home after proper training, potentially making them more accessible and less disruptive to patients' lives.

What evidence suggests that Pozelimab/Cemdisiran might be an effective treatment for inclusion body myositis?

Research has shown that the combination of Pozelimab and Cemdisiran, which participants in this trial will receive, may improve certain symptoms in patients. This treatment has improved tiredness, physical abilities, and overall quality of life, which are crucial for individuals with muscle-related conditions. Although no direct evidence exists for its effectiveness in Inclusion Body Myositis, these positive results in related areas suggest potential benefits. The treatment targets specific pathways that could reduce inflammation and muscle damage. Early findings are promising, but further research is needed to confirm its effectiveness for this specific condition. ^{1 3 4 6 7}

Who Is on the Research Team?

Yessar M Hussain, M.D.

Principal Investigator

Austin Neuromuscular Center

Are You a Good Fit for This Trial?

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

Known contraindication to meningococcal and pneumococcal vaccines

I have a condition affecting my movement.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06479863

NCT06479863 | Efficacy and Safety of Pozelimab and ... This is a pilot study of 10 patients to receive Pozelimab 200mg/Cemdisiran 200 mg SC injections every 4 weeks for 104 weeks.

2. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0MPr00000084UfMAI/nct06479863

Efficacy and Safety of Pozelimab and Cemdisiran ... To evaluate the efficacy of Pozelimab/Cemdisiran combination therapy in patients with sIBM.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40708708/

Safety, Efficacy, and Patient-Reported Outcomes From a ... The combination therapy maintained improvements in patient-reported fatigue, physical functioning, and QoL throughout the OLTP. Conclusion: ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06479863/efficacy-and-safety-of-pozelimab-and-cemdisiran-combination-therapy-in-patients-with-sporadic-inclusion-body-myositis

Efficacy and Safety of Pozelimab and Cemdisiran ... To evaluate the efficacy of Pozelimab/Cemdisiran combination therapy in patients with sIBM.

5. withpower.com withpower.com/trial/early-phase-1-myositis-inclusion-body-6-2024-d0d11

Pozelimab + Cemdisiran for Inclusion Body Myositis The available research does not provide specific data on the effectiveness of Pozelimab + Cemdisiran for Inclusion Body Myositis. Instead, it discusses other ...

6. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy00000019vrEAA/nct06479863

Efficacy and Safety of Pozelimab and Cemdisiran ... To evaluate the efficacy of Pozelimab/Cemdisiran combination therapy in patients with sIBM.

7. go.drugbank.com go.drugbank.com/drugs/DB16121/clinical_trials?conditions=DBCOND0166962%2CDBCOND0016324&phase=1&purpose=treatment&status=recruiting

Cemdisiran Recruiting Phase 1 Trials for Myopathy ... Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Sporadic Inclusion Body Myositis.