Efgartigimod for Guillain-Barré Syndrome

Overseen By Kelsey Moulton

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chafic Karam

Must not be taking: Investigational drugs

Disqualifiers: Pregnancy, Severe infections, IgG deficiency, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 1 week

30 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

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

What data supports the effectiveness of the drug Efgartigimod for Guillain-Barré Syndrome?

Efgartigimod has shown effectiveness in treating generalized myasthenia gravis, a condition with some similarities to Guillain-Barré Syndrome, by reducing disease symptoms and improving muscle strength. It works by lowering levels of harmful antibodies in the body, which may also be beneficial for other autoimmune disorders. ^{1 2 3 4 5}

Is efgartigimod generally safe for humans?

Efgartigimod has been generally well tolerated in clinical trials for generalized myasthenia gravis, with most side effects being mild to moderate. ^{3 4 5 6 7}

How does the drug Efgartigimod differ from other treatments for Guillain-Barré Syndrome?

Efgartigimod is unique because it targets the neonatal Fc receptor (FcRn), reducing the levels of harmful antibodies in the body, which is different from traditional treatments like intravenous immunoglobulin (IVIg) that work by providing a broad range of antibodies to neutralize harmful ones. This targeted approach may offer a more precise way to manage the condition. ^{8 9 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to evaluate the safety and effectiveness of Efgartigimod in patients with Guillain-Barre syndrome (GBS). The main questions it aims to answer are: * Is Efgartigimod a safe treatment option for GBS patients? * Does treatment with Efgartigimod improve patient outcomes? In addition to standard-of-care procedures and assessments, participants will: * Undergo seven blood draws during hospitalization and in four follow-up study visits to evaluate the concentration of neurofilament light chain, a protein that is elevated in patients with Guillain-Barré syndrome. The presence of neurofilament light chain is believed to be indicative of damage to the nervous system, with higher levels resulting from greater damage. * Complete the Columbia Suicide Severity Rating Scale (C-SSRS) to monitor any suicidal ideation or behaviors during the course of the study.

Research Team

Chafic Karam, MD

Principal Investigator

Staff Physician and Associate Professor of Clinical Neurology

Colin Quinn, MD

Principal Investigator

Staff Physician and Associate Professor of Clinical Neurology

Eligibility Criteria

This trial is for adults over 18 with Guillain-Barré Syndrome (GBS) who started experiencing weakness due to GBS within the last two weeks. Participants must be able to follow the study's procedures and agree to stay in the study for its duration. They should not have other health conditions that could interfere with the trial.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

Provision of signed and dated informed consent form

I have been diagnosed with Guillain-Barré Syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Efgartigimod or IVIg treatment. Efgartigimod is administered on days 1 and 5, with placebo on days 2-4. IVIg is administered daily for 5 days.

1 week

Daily visits for 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of GBS Disability Scale, NIS, and I-RODS.

48 weeks

4 follow-up visits

Long-term follow-up

Participants are monitored for adverse events and biomarker levels through study completion.

3 years

Treatment Details

Interventions

• Efgartigimod Alfa-Fcab

Trial Overview The trial is testing Efgartigimod, a new potential treatment for GBS, against standard Intravenous Immunoglobulin (IVIg) therapy. It aims to determine if Efgartigimod is safe and can improve patient outcomes by monitoring protein levels indicative of nerve damage and assessing any changes in mental health status.

Participant Groups

Group I: Efgartigimod Alfa-Fcab Experimental Treatment 1 Intervention

20mg/kg of Intravenous efgartigimod on days 1 and 5, with normal saline administered as placebo on days 2-4

Group II: Intravenous Immunoglobulin (IVIg) Active Control 1 Intervention

0.4g/kg of IVIg daily for 5 days

Efgartigimod Alfa-Fcab is already approved in United States, European Union for the following indications:

Approved in United States as Vyvgart for:

• Generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive
• Chronic inflammatory demyelinating polyneuropathy (CIDP)

Approved in European Union as Vyvgart for:

• Generalized myasthenia gravis (gMG)

Who Is Running the Clinical Trial?

Chafic Karam

Lead Sponsor

Trials

1

Recruited

30+

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

Findings from Research

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, 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 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 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]

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]

Intravenous immunoglobulin (IVIg) therapy may help treat conditions like Guillain-Barré syndrome by inhibiting the binding of cholera toxin to GM1, which is linked to disease development in some patients.

The study suggests that the mechanism of IVIg involves its variable region binding to both anti-GM1 antibodies and cholera toxin, potentially neutralizing harmful effects of the autoantibody, indicating a specific action in the treatment of these neuropathies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible mechanism of intravenous immunoglobulin treatment on anti-GM1 antibody-mediated neuropathies. Yuki, N., Miyagi, F.[2006]

In a study of 38 patients with Guillain-Barré syndrome, high affinity anti-GM1 IgG antibodies were linked to a higher frequency of axonal degeneration, indicating a potential mechanism for nerve damage in these patients.

The predominant IgG subclass for high affinity anti-GM1 antibodies was IgG1, while the presence of anti-Campylobacter jejuni antibodies did not correlate with specific disease patterns, suggesting that not all antibodies play a role in the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Affinity of anti-GM1 antibodies in Guillain-Barré syndrome patients. Deisenhammer, F., Keir, G., Pfausler, B., et al.[2019]

Intravenous immunoglobulin (IVIg) treatment effectively prevented paralysis in a model of Guillain-Barré syndrome, demonstrating its potential as a therapeutic intervention.

The study found that intact-type IVIg was more effective than F(ab')2 fragments, suggesting that the Fc portion of IVIg plays a crucial role in modulating the immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc portion of intravenous immunoglobulin suppresses the induction of experimental allergic neuritis. Miyagi, F., Horiuchi, H., Nagata, I., et al.[2019]

In a study of 121 patients with Guillain-Barré syndrome (GBS), 32 patients were found to have anti-GM1 IgG antibodies, and all of these also showed activity against a mixture of GM1 and phosphatidic acid (GM1/PA), suggesting a potential link to the disease's mechanism.

Notably, 78% of the patients with anti-GM1 IgG antibodies had stronger binding activity to GM1/PA than to GM1 alone, indicating that this binding may play a significant role in the pathogenesis of GBS and could influence diagnostic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding of immunoglobulin G antibodies in Guillain-Barré syndrome sera to a mixture of GM1 and a phospholipid: possible clinical implications. Kusunoki, S., Morita, D., Ohminami, S., et al.[2015]

Intravenous immunoglobulin (IVIG) treatment is effective in managing autoimmune disorders like myasthenia gravis (MG), but the specific components responsible for its action are not fully understood.

The study identified that a small, disease-specific fraction of immunoglobulin within IVIG is crucial for its immunosuppressive effects, highlighting the importance of this fraction in the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A disease-specific fraction isolated from IVIG is essential for the immunosuppressive effect of IVIG in experimental autoimmune myasthenia gravis. Fuchs, S., Feferman, T., Meidler, R., et al.[2008]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome. [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 Alfa in Generalised Myasthenia Gravis: A Profile of Its Use. [2023]

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

Efgartigimod: First Approval. [2022]

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

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

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

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

Possible mechanism of intravenous immunoglobulin treatment on anti-GM1 antibody-mediated neuropathies. [2006]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Affinity of anti-GM1 antibodies in Guillain-Barré syndrome patients. [2019]

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

Fc portion of intravenous immunoglobulin suppresses the induction of experimental allergic neuritis. [2019]

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

Binding of immunoglobulin G antibodies in Guillain-Barré syndrome sera to a mixture of GM1 and a phospholipid: possible clinical implications. [2015]

12. Netherlands pubmed.ncbi.nlm.nih.gov

A disease-specific fraction isolated from IVIG is essential for the immunosuppressive effect of IVIG in experimental autoimmune myasthenia gravis. [2008]