Efgartigimod for Myasthenia Gravis

Overseen By Eduardo Ng

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University Health Network, Toronto

Must be taking: AChE inhibitors, steroids, NSISTs

Must not be taking: Rituximab, Eculizumab

Disqualifiers: Pregnancy, Hepatitis, HIV, 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: 24

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is to study the efficacy, safety and tolerability of efgartigimod in patients with seronegative generalized myasthenia gravis. This is an open label study. There will be 30 participants to enroll at University Health Network Toronto General Hospital. Study duration is 43 weeks from screening to end of study.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current myasthenia gravis medications, such as AChE inhibitors, steroids, and certain immunosuppressants, for at least one month before screening.

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

Efgartigimod has been shown in clinical trials to significantly reduce disease symptoms and improve muscle strength and quality of life in patients with generalized myasthenia gravis. It was well tolerated, with most side effects being mild to moderate, and has been approved for use in several countries. ^{1 2 3 4 5}

Is efgartigimod safe for humans?

Efgartigimod, also known as Vyvgart, has been generally well tolerated in clinical trials for myasthenia gravis, with most side effects being mild to moderate. ^{1 3 4 5 6}

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, helping to improve muscle strength and quality of life for people with myasthenia gravis. It is administered intravenously and has shown rapid and lasting benefits in clinical trials. ^{1 3 4 5 7}

Research Team

Vera Bril, MD

Principal Investigator

Toronto General Hospital

Eligibility Criteria

This trial is for individuals with seronegative generalized myasthenia gravis, a condition causing muscle weakness. Participants will be treated at the University Health Network Toronto General Hospital and must commit to a study duration of 43 weeks.

Inclusion Criteria

My myasthenia gravis is moderate to severe.

Evidence of signed and dated informed consent document(s) indicating willingness to comply with the protocol, complete study assessments, and return for follow-up visits

My myasthenia gravis is moderate to severe.

Exclusion Criteria

I have tested positive for HBV, HCV, or HIV.

I had my thymus gland removed within the last 3 months.

I have not had immunoglobulin or plasma exchange in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Run-in

Participants undergo a run-in period to stabilize conditions before baseline

3 weeks

1 visit (in-person)

Induction

Participants receive weekly induction treatment with efgartigimod

3 weeks

3 visits (in-person)

Maintenance

Participants receive maintenance treatment every 2 weeks

31 weeks

15 visits (in-person)

Observation

Participants are monitored with 4 visits during the observation period

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Efgartigimod

Trial Overview The trial is testing efgartigimod's effectiveness, safety, and tolerability in treating muscle weakness due to myasthenia gravis. It's an open-label study which means everyone knows they're getting efgartigimod; no placebos are used.

Participant Groups

Group I: efgartigimod Experimental Treatment 1 Intervention

active treatment with efgartigimod.

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?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

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 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]

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 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 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 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]

References

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

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

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

Clinical efficacy and safety of efgartigimod for treatment of myasthenia gravis. [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. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

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