Efgartigimod for Myositis

(ALKIVIA Trial)

Recruiting in Palo Alto (17 mi)

+417 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: argenx

Disqualifiers: Active infection, Autoimmune disease, Malignancy, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing an injectable medication called efgartigimod PH20 SC in people with certain muscle inflammation diseases. The goal is to see if it helps improve their condition by lowering harmful proteins in their blood. The study focuses on patients with specific subtypes of these diseases who often don't respond well to usual treatments. Efgartigimod was developed for autoimmune diseases and has been approved for treating a specific muscle condition in adults.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants must be on a permitted background treatment for idiopathic inflammatory myopathy. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Efgartigimod for treating myositis?

Research shows that Efgartigimod can restore muscle function in a mouse model of immune-mediated necrotizing myopathy, a severe form of myositis. This suggests it may help reduce harmful antibodies and improve muscle function in similar conditions. ^{1 2 3 4 5}

Is efgartigimod safe for humans?

Efgartigimod has been generally well tolerated in clinical trials for conditions like generalized myasthenia gravis, with most side effects being mild to moderate. ^{1 6 7 8 9}

How is the drug Efgartigimod PH20 SC different from other treatments for myositis?

Efgartigimod PH20 SC is unique because it works by reducing harmful antibodies in the body through a mechanism that prevents their recycling, which is different from traditional treatments like intravenous immunoglobulin (IVIg) that mainly focus on modulating the immune response. This drug is administered subcutaneously (under the skin), offering a potentially more convenient option compared to the intravenous route of other therapies. ^{1 3 4 10 11}

Research Team

Eligibility Criteria

Adults with active Idiopathic Inflammatory Myopathy (IIM), specifically dermatomyositis, immune-mediated necrotizing myopathy, or polymyositis including antisynthetase syndrome. Participants must have muscle weakness and abnormal enzyme levels indicating IIM. They should be on stable IIM treatments and use contraception if applicable. Exclusions include other primary causes of muscle weakness, severe infections like HIV/HBV/HCV, recent major surgery risks, drug abuse history, pregnancy/lactation intentions during the study period.

Inclusion Criteria

Contraceptive use consistent with local regulations, where available, for individuals participating in clinical studies. Women of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline before receiving investigational medicinal product (IMP)

Abnormal levels of at least 1 of the following enzymes: creatine kinase (CK), aldolase, lactate dehydrogenase, aspartate aminotransaminase (AST), alanine aminotransferase (ALT), based on central laboratory results

I was diagnosed with dermatomyositis before I turned 18, and it was within the last 5 years.

Exclusion Criteria

You have had an allergic reaction to the experimental medication or any of its ingredients.

You have another autoimmune disease that could make it difficult to accurately evaluate your symptoms of idiopathic inflammatory myopathy (IIM) or might put you at increased risk.

Positive serum test at screening for active viral infection with any of the following conditions: Hepatitis B virus (HBV); Hepatitis C virus (HCV); HIV

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive efgartigimod PH20 SC or placebo on top of background treatment

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Efgartigimod PH20 SC (Monoclonal Antibodies)
• PBO ()

Trial Overview The trial is testing Efgartigimod PH20 SC's effectiveness compared to a placebo in improving symptoms of IIM as measured by Total Improvement Score (TIS). It includes adults diagnosed with certain subtypes of IIM who will receive either the investigational medication or a placebo while continuing their standard treatment for IIM.

Participant Groups

Group I: EFG PH20 SC Experimental Treatment 1 Intervention

participants receiving efgartigimod PH20 SC on top of background treatment

Group II: PBO PH20 SC Placebo Group 1 Intervention

participants receiving placebo PH20 SC on top of background treatment

Efgartigimod PH20 SC is already approved in Japan, China for the following indications:

Approved in Japan as VYVDURA for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

Approved in China as Efgartigimod alfa injection (subcutaneous injection) for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

Who Is Running the Clinical Trial?

argenx

Lead Sponsor

Trials

76

Recruited

11,500+

Tim Van Hauwermeiren

argenx

Chief Executive Officer since 2008

B.Sc. and M.Sc. in Bioengineering from Ghent University, Executive MBA from The Vlerick School of Management

Dr. Peter Ulrichts

argenx

Chief Medical Officer since 2023

MD from Maastricht University, PhD in Molecular Immunology from Maastricht University

Findings from Research

Efgartigimod effectively reduces levels of pathogenic anti-HMGCR autoantibodies and total IgG in a humanized mouse model of immune-mediated necrotizing myopathies, demonstrating significant therapeutic potential.

In both preventive and therapeutic settings, efgartigimod not only prevents muscle fiber necrosis but also promotes muscle fiber regeneration, leading to restored muscle strength, which supports further clinical trials in patients with IMNM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod restores muscle function in a humanized mouse model of immune-mediated necrotizing myopathy. Julien, S., van der Woning, B., De Ceuninck, L., et al.[2023]

Serum levels of B cell activating factor (BAFF) were significantly higher in patients with myositis compared to healthy controls, suggesting a potential role in the disease's pathology.

Higher BAFF levels were associated with specific autoantibodies, particularly anti-Jo-1, and correlated with muscle damage markers, indicating that BAFF may serve as a therapeutic target in myositis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Krystufková, O., Vallerskog, T., Helmers, SB., et al.[2009]

Efgartigimod alfa is the first neonatal Fc receptor antagonist approved for treating generalized myasthenia gravis (gMG), showing significant and rapid improvements in muscle strength and quality of life in a phase 3 trial with a placebo group.

The treatment was generally well tolerated, with most side effects being mild to moderate, indicating a favorable safety profile for patients with gMG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod Alfa in Generalised Myasthenia Gravis: A Profile of Its Use. Heo, YA.[2023]

Efgartigimod, a first-in-class neonatal Fc receptor antagonist, received its first approval in the USA in December 2021 for treating generalized myasthenia gravis in adults who are positive for anti-acetylcholine receptor antibodies.

The drug is also being evaluated for other autoimmune diseases and has been approved in Japan for generalized myasthenia gravis patients regardless of antibody status, indicating its potential broad application in autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod: First Approval. Heo, YA.[2022]

Efgartigimod, a new treatment that reduces pathogenic IgG autoantibodies, showed promising results in three patients with both stiff-person syndrome (SPS) and myasthenia gravis (MG) over a 12-week treatment period, leading to symptom improvement.

This study suggests that efgartigimod could be a potential therapy for SPS and other autoimmune neurological disorders, as it demonstrated efficacy in alleviating symptoms associated with both conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome. Di Stefano, V., Alonge, P., Rini, N., et al.[2023]

Efgartigimod, a human IgG1 antibody, significantly improved symptoms in patients with generalized myasthenia gravis, with 68% of treated patients showing a meaningful response compared to only 30% in the placebo group, indicating strong efficacy.

The treatment was well tolerated, with similar rates of adverse events between efgartigimod and placebo groups, suggesting it is a safe option for patients, with no deaths reported during the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Howard, JF., Bril, V., Vu, T., et al.[2022]

The study utilized artificial intelligence to evaluate treatment responses in patients with Inflammatory Idiopathic Myopathies (IIM) receiving intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (20%SCIg), identifying key predictors of treatment success based on muscle strength and disease activity scores.

Results indicated that muscle strength improvement, as measured by the MMT8 score, was associated with the presence of dysphagia and skin disorders, suggesting that IVIg therapy may be more effective in patients with active systemic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A machine learning analysis to predict the response to intravenous and subcutaneous immunoglobulin in inflammatory myopathies. A proposal for a future multi-omics approach in autoimmune diseases. Danieli, MG., Tonacci, A., Paladini, A., et al.[2022]

In a study of 13 treatment-resistant patients with inflammatory myopathies, high-dose intravenous immunoglobulin (IVIG) treatment led to improved muscle function in only three patients and decreased creatinine kinase (CK) levels in five, indicating limited efficacy.

Despite some clinical improvements, the study found no significant changes in key immunological markers in muscle biopsies after IVIG treatment, suggesting that IVIG may not effectively modulate the immune response in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies. Barbasso Helmers, S., Dastmalchi, M., Alexanderson, H., et al.[2022]

References

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

Efgartigimod restores muscle function in a humanized mouse model of immune-mediated necrotizing myopathy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Clinical benefits and immunopathological correlates of intravenous immune globulin in the treatment of inflammatory myopathies. [2005]

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

Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. [2009]

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

Intravenous immunoglobulin in patients with anti-GAD antibody-associated neurological diseases and patients with inflammatory myopathies: effects on clinicopathological features and immunoregulatory genes. [2018]

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. New Zealand pubmed.ncbi.nlm.nih.gov

Efgartigimod Alfa in Generalised Myasthenia Gravis: A Profile of Its Use. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Efgartigimod: First Approval. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A machine learning analysis to predict the response to intravenous and subcutaneous immunoglobulin in inflammatory myopathies. A proposal for a future multi-omics approach in autoimmune diseases. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies. [2022]