Efgartigimod IV for Myasthenia Gravis

(ADAPT Jr Trial)

Recruiting at 84 trial locations

Overseen By Sabine s Coppieters, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: argenx

Must be taking: Immunosuppressants, Steroids, AChE inhibitors

Must not be taking: Monoclonal antibodies, IVIg, PLEX

Disqualifiers: MGFA class I, IVb, V, 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: Unknown

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this trial is to investigate the PK, PD, safety, and activity of efgartigimod IV in children and adolescents aged from 2 to less than 18 years of age with gMG. Trial details include: * The maximum trial duration for each individual participant will be approximately 28 weeks * The treatment duration will be 8 weeks for the dose-confirmatory part (Part A) and 18 weeks for the treatment response-confirmatory part (Part B)

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that participants should be on stable gMG therapy before screening. It's best to discuss your current medications with the trial team to understand any specific requirements.

What data supports the effectiveness of the drug Efgartigimod IV for treating myasthenia gravis?

Research shows that Efgartigimod IV significantly reduces symptoms and improves muscle strength and quality of life in patients with generalized myasthenia gravis. It has been well tolerated in clinical trials, with most side effects being mild to moderate. ^{1 2 3 4 5}

Is Efgartigimod IV safe for humans?

Efgartigimod IV, used for treating myasthenia gravis, has been generally well tolerated in clinical trials, with most side effects being mild to moderate. ^{1 2 3 4 5}

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

Efgartigimod IV is unique because it is the first drug that works by blocking the neonatal Fc receptor, which reduces harmful antibodies in the body, specifically for treating generalized myasthenia gravis. This mechanism is different from other treatments and has shown to quickly improve muscle strength and quality of life in patients. ^{2 3 4 6 7}

Eligibility Criteria

This trial is for children and adolescents aged 2 to less than 18 with Generalized Myasthenia Gravis (gMG). They must have tried other treatments without success, not be pregnant, use contraception consistently, and not have had recent major surgery or certain infections. Those with mild gMG or severe muscle weakness from other causes can't join.

Inclusion Criteria

I agree not to donate sperm during the trial.

I have been diagnosed with Generalized Myasthenia Gravis.

Female participants must have a negative pregnancy test.

Exclusion Criteria

I have had a major surgery or serious disease recently.

I have had, or will have, a thymectomy within 3 months of joining the trial.

You are allergic to efgartigimod or any of its ingredients.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive efgartigimod IV for dose-confirmatory purposes

8 weeks

Treatment Part B

Participants continue receiving efgartigimod IV for treatment response-confirmatory purposes

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Efgartigimod IV

Trial Overview The study tests Efgartigimod IV in young patients with gMG over approximately 28 weeks. It has two parts: an initial dose-confirmatory phase lasting 8 weeks and a subsequent treatment response-confirmatory phase of 18 weeks to assess the drug's effects on their condition.

Participant Groups

Group I: Efgartigimod Experimental Treatment 1 Intervention

Patients receiving efgartigimod intravenous (IV) treatment

Efgartigimod IV 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

Approved in European Union as Vyvgart for:

• Generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive

Approved in United States as Vyvgart Hytrulo for:

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

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, 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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]