Efgartigimod for Myasthenia Gravis

Recruiting in Palo Alto (17 mi)

Overseen by Vera Bril, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 4 Jurisdictions

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}

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

I am 18 years old or older.

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.

Trial 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 (Monoclonal Antibodies)

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University Health Network, Division of Neurology, Toronto General Hospital Toronto, Canada

Who Is Running the Clinical Trial?

University Health Network, Toronto Lead Sponsor

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] Multiple novel therapies have been approved for patients with myasthenia gravis. Our aim is to describe the early experience of efgartigimod use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG).

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

Clinical efficacy and safety of efgartigimod for treatment of myasthenia gravis. [2023] Treatment of acute exacerbations and refractory myasthenia gravis (MG) remains challenging despite advances in immunotherapy. Frequent use of plasmapheresis and immunoglobulins are associated with adverse events and strain on resources. The neonatal Fc receptor (FcRn) facilitates IgG recycling and FcRn antagonism enhances the degradation of IgG pathogenic autoantibodies without compromising adaptive and innate immunity. Efgartigimod, an FcRN antagonist, has been shown in well-designed clinical trials to improve clinical status and reduce autoantibody levels without significant safety concerns. Efgartigimod has received approvals for use in the United States, Japan and Europe. It is plausible that efgartigimod is effective across different subgroups and varied spectrums of MG severity. Novel strategies involving FcRn modulation and long-term follow-up studies will help provide further insights and expand the therapeutic repertoire.

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

Efgartigimod: First Approval. [2022] Efgartigimod (efgartigimod alfa-fcab, Vyvgart™) is a first-in-class neonatal Fc receptor antagonist being developed by argenx for the treatment of autoimmune diseases including myasthenia gravis. In December 2021, intravenous efgartigimod received its first approval in the USA for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive. Intravenous efgartigimod has also been evaluated for generalized myasthenia gravis in various other countries, with the agent subsequently approved in Japan in January 2022 for generalized myasthenia gravis patients regardless of antibody status and in preregistration stage in the EU. Several clinical studies of intravenous and subcutaneous formulation of efgartigimod are also being investigated for other autoimmune diseases including bullous pemphigoid, chronic inflammatory demyelinating polyradiculoneuropathy, immune thrombocytopenia, autoimmune myositis and pemphigus. This article summarizes the milestones in the development of efgartigimod leading to this first approval for generalized myasthenia gravis.

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

Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. [2020] To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.

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

Efgartigimod Alfa in Generalised Myasthenia Gravis: A Profile of Its Use. [2023] Intravenous efgartigimod alfa (also known as efgartigimod alfa-fcab in the USA; Vyvgart®) is the first neonatal Fc receptor antagonist approved in several countries worldwide, including the USA and EU for the treatment of generalised myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of gMG regardless of antibody status. In the double-blind, placebo-controlled phase 3 ADAPT trial in patients with gMG, efgartigimod alfa significantly and rapidly reduced disease burden and improved muscle strength and quality of life compared with placebo. The clinical benefits of efgartigimod alfa were durable and reproducible. Furthermore, in an interim analysis of the ongoing open-label phase 3 ADAPT+ extension trial, efgartigimod alfa provided consistent clinically meaningful improvements in patients with gMG. Efgartigimod alfa was generally well tolerated, with most adverse events being mild to moderate in severity.

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] There is an unmet need for treatment options for generalised myasthenia gravis that are effective, targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels, in patients with generalised myasthenia gravis.

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] Generalized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 antibody Fc fragment engineered for increased binding affinity to neonatal Fc receptor. The neonatal Fc receptor blockade by efgartigimod competitively inhibits endogenous IgG binding, leading to decreased IgG recycling and increased degradation resulting in lower IgG concentration.