Efgartigimod SC for Myositis

(ALKIVIA+ Trial)

Recruiting at 59 trial locations

Overseen By Sabine s Coppieters, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: argenx

Disqualifiers: Major surgery, Malignancy, Myositis, others

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

240 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to check the safety and effectiveness of an injectable medication called efgartigimod PH20 SC in adults with muscle inflammation who participated in an earlier phase. The medication works by reducing harmful proteins that cause muscle problems.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Efgartigimod has shown effectiveness in reducing symptoms and improving quality of life in patients with generalized myasthenia gravis, a condition similar to myositis in that both are autoimmune disorders. In studies, it significantly reduced disease burden and improved muscle strength, suggesting potential benefits for other autoimmune conditions like myositis. ^{1 2 3 4 5}

Is Efgartigimod SC safe for humans?

Efgartigimod, also known as Vyvgart, has been generally well tolerated in clinical trials for conditions like generalized myasthenia gravis, with most side effects being mild to moderate. ^{1 2 3 4 5}

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

Efgartigimod is unique because it works by reducing harmful antibodies in the body through a specific mechanism that targets the neonatal Fc receptor, which is different from other treatments like intravenous immunoglobulin (IVIG) that modulate the immune system in various ways. This approach may offer a novel way to restore muscle function in myositis patients. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults with active Idiopathic Inflammatory Myopathy (IIM) who completed the ARGX-113-2007 study. Participants must be able to consent, follow the study plan, and use contraception if of childbearing potential. Exclusions include planned major surgery, new medical conditions that risk safety or skew results, known drug hypersensitivity, any cancer except basal cell skin carcinoma, or previous discontinuation from the related trial.

Inclusion Criteria

Has completed trial ARGX-113-2007

Being capable of providing signed informed consent and complying with protocol requirements

Agrees to use contraceptive measures consistent with local regulations and women of childbearing potential must have a negative urine pregnancy test at baseline before receiving the investigational medicinal product

Exclusion Criteria

I have not developed any new or recurrent cancer, except for basal cell skin cancer.

Known hypersensitivity reaction to investigational medicinal product or 1 of its excipients

Permanent discontinuation of IMP in ARGX-113-2007, or met the permanent discontinuation criteria at the rollover visit

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive efgartigimod PH20 SC on top of background treatment

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Long-term safety, tolerability, and efficacy of efgartigimod PH20 SC are assessed

Long-term

Treatment Details

Interventions

• Efgartigimod

Trial Overview The trial tests long-term safety and effectiveness of a subcutaneous injection called efgartigimod PH20 SC in those with IIM. It's for people who've had it before in an earlier phase of research and looks at how well they tolerate it over time as well as its ongoing benefits.

Participant Groups

Group I: EFG PH20 SC Experimental Treatment 1 Intervention

participants receiving efgartigimod PH20 SC on top of background treatment

Efgartigimod is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vyvgart for:

• Generalized Myasthenia Gravis (gMG)

Approved in United States as Vyvgart for:

• Generalized Myasthenia Gravis (gMG)
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Approved in Canada as Vyvgart for:

• Generalized Myasthenia Gravis (gMG)

Approved in Japan as Vyvgart for:

• Generalized Myasthenia Gravis (gMG)

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 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 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 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 was found to be safe and well-tolerated in a phase 2 study involving 24 patients with generalized myasthenia gravis, with no serious adverse events reported.

The treatment led to a significant reduction in pathogenic IgG autoantibodies and resulted in a rapid and long-lasting improvement in disease symptoms for 75% of patients, suggesting its potential as an effective therapy for myasthenia gravis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Howard, JF., Bril, V., Burns, TM., et al.[2020]

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]

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]

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]

Intravenous immunoglobulin (IVIg) treatment significantly improved clinical scores in patients with Stiff-Person Syndrome (SPS) and dermatomyositis (DM) over 3 months, while scores returned to baseline when switched to placebo, indicating its efficacy in these conditions.

In addition to clinical improvements, IVIg treatment led to notable changes in tissue markers, including reduced inflammation and alterations in immunoregulatory genes, demonstrating its mechanism of action in restoring tissue health.

NCBI (Pubmed)

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. Dalakas, MC.[2018]

References

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

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

2. Germany pubmed.ncbi.nlm.nih.gov

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

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

Efgartigimod: First Approval. [2022]

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

Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. [2020]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

Mechanisms of action of intravenous immunoglobulin in inflammatory muscle disease. [2021]

10. 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]