Efgartigimod for Myasthenia Gravis

Overseen By Alyssa Avilez, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: Cholinesterase inhibitors

Must not be taking: C5-complement inhibitors

Disqualifiers: Active infection, Intubation, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study plans to learn more about if the drug efgartigimod can be used in the hospital to treat exacerbations in participants with myasthenia gravis (MG). Efgartigimod has been approved by the FDA for ongoing (chronic) treatment of generalized MG in adult patients who are anti-acetylcholine receptor (AChR) antibody positive but has not been studied in the treatment of worsening weakness requiring hospital admission (known as "exacerbation"). This investigation aims to see if using efgartigimod in this way improves symptoms and recovery from exacerbation, and how it affects certain MG markers in the blood. The main questions it aims to answer are: * Is efgartigimod effective as a hospital-administered acute therapy for participants with worsening MG (MG exacerbation) who require hospitalization? * Will efgartigimod lead to clinical improvement with a similar reduction in validated research scales, such as the Quantitative MG (QMG) scale, as standard of care therapies? Participants will receive 4 doses of efgartigimod over the course of 4 weeks with an additional follow-up visit at the clinic.

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 excludes those who have used certain treatments like IVIG, plasma exchange, or efgartigimod recently. It also excludes those using specific medications like ravulizumab or eculizumab.

Is efgartigimod safe for humans?

Efgartigimod has been generally well tolerated in clinical trials for myasthenia gravis, with most side effects being mild to moderate. It has been approved for use in several countries, indicating a favorable safety profile. ^{1 2 3 4 5}

How is the drug efgartigimod different from other treatments for myasthenia gravis?

Efgartigimod is unique because it is the first drug that works by blocking the neonatal Fc receptor, which reduces harmful antibodies in the body. This mechanism helps improve muscle strength and quality of life for patients with myasthenia gravis, and it is administered intravenously. ^{1 3 4 6 7}

What data supports the effectiveness of the drug Efgartigimod for Myasthenia Gravis?

Efgartigimod has been shown to significantly reduce disease symptoms and improve muscle strength and quality of life in patients with generalized myasthenia gravis, as demonstrated in the phase 3 ADAPT trial. The benefits were consistent and well-tolerated, with most side effects being mild to moderate. ^{1 3 4 6 7}

Who Is on the Research Team?

Thomas Ragole, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for hospitalized adults with myasthenia gravis (MG) experiencing a worsening of symptoms, known as an exacerbation. Participants must have MG that's confirmed by specific antibodies. Details on who can't join are not provided.

Inclusion Criteria

Abnormal single fiber EMG

Abnormal decrement on slow repetitive nerve stimulation testing

Quantitative Myasthenia Gravis (QMG) scale ≥ 11

Exclusion Criteria

I am currently using ravulizumab or eculizumab.

Intubation prior to ability to sign informed consent or intubation within 24 hours of hospitalization

I don't have health issues that could affect study assessments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive 4 doses of efgartigimod via intravenous (IV) infusion on days 1, 4, 11, and 18

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at day 32

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Efgartigimod

Trial Overview The study tests if efgartigimod, already approved for chronic MG treatment, is effective when given in the hospital to treat acute MG exacerbations. Patients will receive four doses over four weeks and be monitored using the QMG scale.

How Is the Trial Designed?

Group I: Efgartigimod Experimental Treatment 1 Intervention

Participants receive 4 doses of efgartigimod via intravenous (IV) infusion over the course of the study on days 1, 4, 11 and 18.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

argenx

Industry 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

Published Research Related to This Trial

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]

In a study of 37 patients with acetylcholine receptor antibody-positive generalized myasthenia gravis, 72% experienced a significant improvement in daily living activities after one cycle of efgartigimod, indicating its efficacy in managing symptoms.

Efgartigimod treatment resulted in a substantial reduction in IgG levels and was generally well-tolerated, with only mild side effects reported, although one patient had to discontinue due to a Clostridium difficile infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and outcomes with efgartigimod use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice. Katyal, N., Halldorsdottir, K., Govindarajan, R., et al.[2023]

Efgartigimod, an engineered antibody, significantly improves muscle function and strength in patients with generalized myasthenia gravis (gMG), as shown by notable enhancements in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores over a 10-week period.

Improvements were observed across all muscle function subdomains (bulbar, ocular, limb/gross motor, and respiratory) within 1 to 2 weeks after the first infusion, correlating with reduced levels of pathogenic IgG, indicating its mechanism of action in decreasing autoantibody levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study. Bril, V., Howard, JF., Karam, C., et al.[2023]

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 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 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, an FcRn antagonist, has been shown in clinical trials to effectively improve clinical status and reduce autoantibody levels in patients with myasthenia gravis, with no significant safety concerns reported.

This treatment has received regulatory approvals in the United States, Japan, and Europe, suggesting its potential effectiveness across various subgroups and severities of myasthenia gravis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of efgartigimod for treatment of myasthenia gravis. Sivadasan, A., Bril, V.[2023]

Citations

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

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

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

Safety and outcomes with efgartigimod use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice. [2023]

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

Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study. [2023]

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

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

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

Efgartigimod: First Approval. [2022]

6. 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]

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

Clinical efficacy and safety of efgartigimod for treatment of myasthenia gravis. [2023]