Efgartigimod for Myasthenia Gravis

(ADAPT Jr SC Trial)

Recruiting at 8 trial locations

Overseen By Sabine s Coppieters, MD

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: argenx

Must be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Pregnancy, Infection, Autoimmune disease, Cancer, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

12 Participants Needed

Trial Summary

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 a stable dose of their current MG therapy for at least one month before screening. It's best to discuss your specific medications with the study team.

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 has been generally well tolerated in clinical trials for myasthenia gravis, with most side effects being mild to moderate. ^{1 2 4 5 6}

What makes the drug Efgartigimod PH20 SC unique for treating Myasthenia Gravis?

Efgartigimod PH20 SC is unique because it is designed to reduce the levels of antibodies that attack the body's own tissues, which is a novel approach for treating Myasthenia Gravis. This drug is administered subcutaneously (under the skin), offering a different route compared to some other treatments that may require intravenous administration. ^{7 8 9 10 11}

What is the purpose of this trial?

The purpose of this study is to measure the pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, and immunogenicity of efgartigimod PH20 SC in pediatric participants with gMG aged 2 to \<18 years. The primary goal is to confirm an appropriate dose of efgartigimod PH20 SC for pediatric patients using PK and PD results from this study. Participants will receive injections of efgartigimod PH20 SC and will be monitored for safety until the end of the study. At the end of the follow-up period, eligible participants may roll over to an open-label extension (OLE) study. The participants will be in the study for up to 14 weeks.

Eligibility Criteria

This trial is for children aged 2 to less than 18 with generalized Myasthenia Gravis (gMG), confirmed by tests. They should understand the study and follow its rules, have tried other gMG treatments without enough improvement, and be on a stable dose of current medications for at least a month. Participants must use birth control if applicable.

Inclusion Criteria

I understand the study requirements and can consent to participate.

Participant agrees to use birth control consistent with local regulations and people of child-bearing potential must have a negative blood pregnancy test at screening and a negative urine pregnancy test before receiving the study drug

I've tried certain medications for my condition without much success but am on a stable treatment plan now.

Exclusion Criteria

I had cancer but have been free of it for over 3 years or was treated successfully for certain cancers.

I have not received a live vaccine in the last 4 weeks.

Positive PCR test for SARS-CoV-2 at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive injections of efgartigimod PH20 SC and are monitored for safety, pharmacokinetics, and pharmacodynamics

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Open-label extension (optional)

Eligible participants may roll over to an open-label extension study for continued treatment

Treatment Details

Interventions

• Efgartigimod PH20 SC

Trial Overview The study tests Efgartigimod PH20 SC in kids with gMG to find the right dose based on how their body absorbs and responds to it. It involves injections of this drug, monitoring over up to 14 weeks, followed by an optional extension phase for further observation.

Participant Groups

Group I: Efgartigimod PH20 SC Experimental Treatment 1 Intervention

Participants aged 12 to \<18 years receiving efgartigimod PH20 SC treatment

Efgartigimod PH20 SC is already approved in European Union, United States, Japan, China for the following indications:

Approved in European Union as VYVGART for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

Approved in United States as VYVGART Hytrulo for:

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

Approved in Japan as VYVDURA for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

Approved in China as Efgartigimod alfa injection (subcutaneous injection) for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

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 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]

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 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 thorough QT study involving 70 healthy volunteers, the GFF metered dose inhaler (MDI) demonstrated no potential for QT prolongation, indicating cardiovascular safety at therapeutic doses.

In a separate study with 237 patients suffering from moderate-to-severe COPD, GFF MDI did not cause significant changes in heart rate or other cardiovascular measures, confirming its safety profile compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular safety profile of a fixed-dose combination of glycopyrrolate and formoterol fumarate delivered via metered dose inhaler using co-suspension delivery technology. Ferguson, GT., Reisner, C., Pearle, J., et al.[2019]

NVA237 (glycopyrronium bromide) demonstrated consistent pharmacokinetics in mild-to-moderate COPD patients, with a steady-state reached within one week of treatment and limited systemic accumulation after repeated once-daily inhalation.

The study showed that plasma exposure to NVA237 was dose-proportional within the 50-200 μg range, indicating its potential for effective dosing without significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of multiple inhaled NVA237 doses in patients with chronic obstructive pulmonary disease (COPD). Sechaud, R., Renard, D., Zhang-Auberson, L., et al.[2019]

The fixed-dose combination of glycopyrrolate and formoterol (GFF MDI) significantly improved lung function in patients with moderate-to-very severe COPD after 7 days of treatment, outperforming monocomponent inhalers and placebo.

Both doses of GFF MDI (72/9.6 μg and 36/9.6 μg) were well tolerated, indicating a favorable safety profile for this combination therapy in managing COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. Reisner, C., Fabbri, LM., Kerwin, EM., et al.[2022]

Glycopyrronium, a long-acting muscarinic antagonist (LAMA), delivered a significantly higher fine particle fraction (42.6%) compared to tiotropium (9.8%), indicating better potential for effective lung deposition in COPD patients.

The study found that glycopyrronium also achieved greater intrathoracic drug deposition (39%) than tiotropium (22%), suggesting it may be more effective for a broader range of COPD severities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery characteristics of a low-resistance dry-powder inhaler used to deliver the long-acting muscarinic antagonist glycopyrronium. Colthorpe, P., Voshaar, T., Kieckbusch, T., et al.[2023]

In a 52-week study involving 1,066 patients with moderate-to-severe COPD, NVA237 (glycopyrronium bromide) significantly improved lung function, with a 97 mL increase in trough FEV(1) at 12 weeks compared to placebo.

NVA237 also reduced the risk of moderate-to-severe COPD exacerbations by 34% and improved patients' dyspnoea and health status, showing comparable efficacy to the standard treatment tiotropium, while maintaining a similar safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study. Kerwin, E., Hébert, J., Gallagher, N., et al.[2022]

References

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

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

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

Efgartigimod: First Approval. [2022]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

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. England pubmed.ncbi.nlm.nih.gov

Cardiovascular safety profile of a fixed-dose combination of glycopyrrolate and formoterol fumarate delivered via metered dose inhaler using co-suspension delivery technology. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of multiple inhaled NVA237 doses in patients with chronic obstructive pulmonary disease (COPD). [2019]

9. England pubmed.ncbi.nlm.nih.gov

A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Delivery characteristics of a low-resistance dry-powder inhaler used to deliver the long-acting muscarinic antagonist glycopyrronium. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study. [2022]