Imvotamab for Inflammatory Myopathies

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: IGM Biosciences, Inc.

Must be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Pregnancy, Breastfeeding, Inclusion body myositis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 50 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests imvotamab to determine its safety and tolerability for people with moderate-to-severe inflammatory myopathies, a group of muscle diseases that cause weakness and inflammation. It targets those who haven't found success with other treatments. Participants will receive imvotamab through an IV. Individuals diagnosed with conditions like polymyositis or dermatomyositis, who still experience active symptoms despite treatment, might be suitable candidates. As a Phase 1 trial, this research aims to understand how imvotamab works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you must be on a stable dose of oral corticosteroids (≤ 30 mg/day of prednisone) for at least 4 weeks before starting the study.

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

Previous studies have examined imvotamab for its safety in treating autoimmune conditions. Research shows that it can effectively target and destroy certain immune cells involved in these diseases. Tests in both humans and animals have shown promising results. However, this study remains in its early stages, so detailed safety information in humans is still being collected.

Participants in earlier studies experienced some side effects, but these were generally manageable. While the exact side effects are still under investigation, ongoing research aims to confirm how well participants can tolerate this treatment. As with any new treatment, close monitoring will help ensure participant safety as researchers gather more information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Imvotamab is unique because it targets inflammatory myopathies in a new way by using a monoclonal antibody that acts on specific immune cells. Unlike traditional treatments such as corticosteroids or immunosuppressive drugs, which can affect the entire immune system, Imvotamab is designed to selectively target and modulate the activity of certain immune cells involved in muscle inflammation. This targeted approach could potentially reduce side effects and improve effectiveness, making researchers excited about its potential to offer a more precise treatment option for patients. Additionally, its intravenous administration may provide a more controlled delivery compared to oral medications.

What evidence suggests that imvotamab might be an effective treatment for inflammatory myopathies?

Research shows that imvotamab, a bispecific antibody, can effectively target and destroy certain immune cells called B cells, which often contribute to inflammatory diseases. In lab studies, imvotamab killed B cells from patients with autoimmune diseases. Similar drugs have proven safe and effective for other immune-related conditions. This trial will study imvotamab in a dose escalation format to evaluate its potential to help people with idiopathic inflammatory myopathies, muscle diseases caused by the immune system attacking the body. Although human data on imvotamab is limited, these early results are promising. ^{1 2 3 4 6}

Who Is on the Research Team?

Rebecca Kunder

Principal Investigator

IGM Biosciences

Are You a Good Fit for This Trial?

This trial is for patients with moderate to severe idiopathic inflammatory myopathies, which include conditions like muscular dystrophy and polymyositis. It's specifically for those who haven't responded well to previous treatments.

Inclusion Criteria

My inflammatory muscle disease hasn't improved after 3 months of treatment with steroids and another immune system medication.

I have been on a stable dose of steroids equivalent to 30 mg/day of prednisone or less for at least 4 weeks.

I have been diagnosed with a specific type of inflammatory muscle disease.

Exclusion Criteria

Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the final dose of imvotamab

Receipt of an investigational therapy less than 12 weeks or 5 drug-elimination half-lives (whichever is longer) prior to first administration of study treatment and during the study

I have inclusion body myositis or myositis related to another connective tissue disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive imvotamab intravenously to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics

50 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Imvotamab

Trial Overview The study is testing the safety and how well people can tolerate Imvotamab, a drug given intravenously (through the vein), in individuals with certain muscle inflammation diseases that have been resistant to other therapies.

How Is the Trial Designed?

Group I: Imvotamab (Dose Escalation) Experimental Treatment 1 Intervention

Imvotamab administered intravenously

Who Is Running the Clinical Trial?

IGM Biosciences, Inc.

Lead Sponsor

Trials

10

Recruited

520+

Published Research Related to This Trial

Recent advancements in identifying circulating autoantibodies have improved the diagnosis and management of idiopathic inflammatory myopathies (IIMs), which include conditions like polymyositis and dermatomyositis.

A multidisciplinary diagnostic approach that integrates clinical evaluations, muscle assessments, and autoantibody testing is recommended for effectively managing patients suspected of having IIMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features and diagnostic tools in idiopathic inflammatory myopathies. Tsamis, KI., Boutsoras, C., Kaltsonoudis, E., et al.[2022]

In a study of 6 adult patients with refractory idiopathic inflammatory myopathies (IIM), rituximab (RTX) treatment led to significant clinical improvement in 5 out of 6 patients after 6 months, demonstrating its efficacy in this challenging condition.

The treatment was generally well tolerated, with only one mild infusion reaction and one case of Herpes zoster infection reported, suggesting a favorable safety profile for RTX in patients with IIM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in refractory idiopathic inflammatory myopathies and antisynthetase syndrome: personal experience and review of the literature. Nalotto, L., Iaccarino, L., Zen, M., et al.[2021]

High-dose pulse dexamethasone is as effective as standard high daily doses of prednisolone for treating idiopathic inflammatory myopathies (IIMs), but with fewer side effects and a longer time to relapse.

Intravenous immunoglobulins (IVIGs) show variable results in IIMs, yet recent evaluations indicate they may be effective for steroid-resistant patients with esophageal involvement, highlighting the need for further research into new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials roundup in idiopathic inflammatory myopathies. Mann, HF., Vencovský, J.[2017]

The understanding of myositis-specific antibodies has advanced the classification of idiopathic inflammatory myopathies (IIMs), leading to new subcategories like necrotizing autoimmune myositis (NAM), which helps in diagnosing and assessing disease severity.

Treatment options for IIMs have expanded beyond glucocorticoids to include steroid-sparing agents, immunoglobulin therapy, and biologics like rituximab, improving management strategies for these autoimmune muscle diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis. Mandel, DE., Malemud, CJ., Askari, AD.[2018]

Rituximab (RTX) was found to be effective in treating refractory idiopathic inflammatory myopathies (IIMs) in 16 out of 30 patients, with a significant reduction in creatine phosphokinase (CPK) levels and corticosteroid (CS) doses over a mean follow-up of 17.2 months.

The treatment was well tolerated, with only 13 adverse events reported, including seven infections, indicating a relatively safe profile for RTX in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in the treatment of refractory inflammatory myopathies in adults: results from the AIR registry. Couderc, M., Gottenberg, JE., Mariette, X., et al.[2022]

In a study of 1637 patients with idiopathic inflammatory myopathy (IIM), 61.5% tested positive for myositis specific autoantibodies (MSAs) or myositis associated autoantibodies (MAAs), indicating that these autoantibodies are common in this condition and can help identify distinct clinical subsets.

Certain autoantibodies, such as anti-TIF1 and anti-Mi-2, are associated with an increased risk of malignancy, while others like anti-SRP are linked to cardiac involvement, highlighting the importance of these autoantibodies as potential biomarkers for disease complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients. Betteridge, Z., Tansley, S., Shaddick, G., et al.[2021]

In a study of 628 patients with idiopathic inflammatory myopathies (IIMs), the overall 10-year survival rate was 75.6%, but the anti-MDA-5-positive subgroup had significantly lower survival rates (58.5% at 10 years), indicating a poorer prognosis for this group.

Key risk factors affecting long-term survival included rapidly progressive interstitial lung disease (RP-ILD) and malignancy, with RP-ILD being particularly detrimental for the anti-MDA-5-positive subgroup, highlighting the need for targeted monitoring and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes and Prognosis Factors in Patients With Idiopathic Inflammatory Myopathies Based on Myositis-Specific Autoantibodies: A Single Cohort Study. Jiang, W., Shi, J., Yang, H., et al.[2023]

Rituximab, an anti-CD20 monoclonal antibody, showed a high response rate in treating inflammatory myopathies (IM), with 75% of patients in this study and 72.5% in the literature reporting a good response, particularly in dermatomyositis cases.

The treatment was generally well tolerated, with no serious adverse events reported; however, infections, especially respiratory tract infections, were the most common side effects, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of dermatomyositis and other inflammatory myopathies. A report of 4 cases and review of the literature. Rios Fernández, R., Callejas Rubio, JL., Sánchez Cano, D., et al.[2017]

Rituximab (RTX) was found to be an effective treatment for 68.8% of 16 Korean patients with refractory idiopathic inflammatory myopathies (IIM), with 75% showing some level of response after 24 weeks, indicating its potential as a therapeutic option.

The treatment was relatively safe, with a low rate of adverse events reported at 25.4 per 1,000 person-years, suggesting that RTX could be a viable alternative for patients who have not responded to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rituximab in Korean Patients with Refractory Inflammatory Myopathies. Ahn, GY., Suh, CH., Kim, YG., et al.[2021]

In a study of 360 patients with inflammatory myopathies, anti-Jo-1 was the most common myositis-specific antibody (MSA) found, and it was linked to a higher occurrence of interstitial lung disease (ILD) and chronic disease course.

Anti-MDA5 was also associated with ILD and skin manifestations, while anti-Mi-2 was connected to classical dermatomyositis and higher creatine kinase (CK) levels, indicating distinct clinical features related to each antibody type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myositis-specific antibodies and clinical characteristics in patients with autoimmune inflammatory myopathies: reported by the Argentine Registry of Inflammatory Myopathies of the Argentine Society of Rheumatology. Gómez, GN., Pérez, N., Braillard Poccard, A., et al.[2021]

In a study of 250 patients with Idiopathic Inflammatory Myositis (IIM), myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) were found in 59.2% of cases, indicating a strong association between these antibodies and distinct clinical phenotypes of IIM.

The study identified specific clinical associations for various antibodies, such as anti-Jo-1 linked to mechanic's hands and interstitial lung disease, and anti-TIF-1γ associated with a higher risk of malignancy, highlighting the importance of antibody testing in understanding and managing IIM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myositis-specific and myositis-associated autoantibodies in a large Indian cohort of inflammatory myositis. Gupta, L., Naveen, R., Gaur, P., et al.[2021]

Intravenous (IVIg) and subcutaneous (SCIg) immunoglobulin therapy significantly improves muscle strength in patients with idiopathic inflammatory myopathy (IIM) and juvenile dermatomyositis (JDM), with a partial response rate of 88.5% for pooled Ig therapy and 96.61% for SCIg treatment.

Ig therapy is generally safe, with a low risk of infection (1.37%), and it can reduce the need for glucocorticoids and immunosuppressants in about 40% of patients, indicating its potential as an effective add-on treatment for refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intravenous and subcutaneous immunoglobulin therapy in idiopathic inflammatory myopathy: A systematic review and meta-analysis. Goswami, RP., Haldar, SN., Chatterjee, M., et al.[2022]

The identification of various autoantibodies associated with idiopathic inflammatory myopathies (IIM) has improved diagnosis and classification, highlighting distinct conditions like dermatomyositis and polymyositis, but challenges remain in achieving consensus among specialists.

New treatment options, including mycophenolate mofetil and rituximab, have shown effectiveness in resistant cases of IIM, while exercise is now recognized as a safe and beneficial practice, although some aggressive forms of the disease, like sporadic inclusion body myositis, remain difficult to treat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classification, diagnosis, and management of idiopathic inflammatory myopathies. Lazarou, IN., Guerne, PA.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06524687?cond=Inflammatory%20Myopathies&viewType=Table&rank=1

A Study of Imvotamab in Active, Refractory Idiopathic ... The purpose of this study is to determine the safety and tolerability of imvotamab in patients with Moderate-Severe Idiopathic Inflammatory Myopathies who have ...

2. veri.larvol.com veri.larvol.com/news/igm-2323/drug

News - imvotamab (IGM-2323) Based on our analysis , antiCD20-CD3 bsAbs are safe and efficacious. Among these drugs, glofitamab, epcoritamab and odronextamab as monotherapy and/or in ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06524687/a-study-of-imvotamab-in-active-refractory-idiopathic-inflammatory-myopathies

A Study of Imvotamab in Active, Refractory Idiopathic ... The purpose of this study is to determine the safety and tolerability of imvotamab in patients with Moderate-Severe Idiopathic Inflammatory ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496724162917

POS1062 THERAPEUTIC POTENTIAL OF IMVOTAMAB, A ... Conclusion: Our preclinical data show imvotamab effectively kills peripheral B cells isolated from AI patients. Moreover, in a non-human primate model, a ...

5. delta.larvol.com delta.larvol.com/Products/?ProductId=41459c52-83e7-4d44-bb5b-ca28ddfa307c

imvotamab (IGM-2323) / IGM Biosciences New trial • P1 data • Myasthenia Gravis • Myositis • Rheumatoid Arthritis • Systemic Lupus Erythematosus · Print · Email · More sharing. Reddit · StumbleUpon.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12031937/

Understanding IgM Structure and Biology to Engineer New ... Imvotamab (IgM-2323) is the first engineered bispecific IgM antibody tested in the clinic. Imvotamab is an IgM pentamer with 10 binding sites ...