ARGX-119 for Congenital Myasthenic Syndromes

Not currently recruiting at 8 trial locations

Overseen By Sabine s Coppieters, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: argenx

Must be taking: Beta agonists

Disqualifiers: Non-DOK7 CMS, Cancer, Pregnancy, others

Compensation: Varies

Number of Visits: Unknown

Duration: 42 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ARGX-119 for individuals with a specific muscle weakness condition known as DOK7-Congenital Myasthenic Syndromes (DOK7-CMS). The study aims to determine the treatment's safety, how the body processes it, and whether it improves participants' well-being and daily functioning. Participants will receive either ARGX-119 or a placebo through an IV every other week. Ideal candidates have a confirmed genetic diagnosis of DOK7-CMS and have used certain breathing medications, such as albuterol, for over three months. As a Phase 1 trial, this research focuses on understanding how ARGX-119 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The protocol does not specify if you need to stop taking your current medications. However, if you are taking oral beta agonists like albuterol, you must have been on them for more than 3 months and agree to stay on the same dose throughout the study.

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

The trial does not specify if you need to stop taking your current medications, but if you are taking oral beta agonists (like albuterol or salbutamol), you must continue on the same stable dose throughout the study.

Is there any evidence suggesting that ARGX-119 is likely to be safe for humans?

A previous study found ARGX-119 to be safe. People with DOK7 congenital myasthenic syndromes, a condition affecting nerve-muscle communication, generally tolerated the treatment well. Another study tested ARGX-119 in healthy individuals and reported similar safety results, with no major safety issues. These findings suggest that ARGX-119 might be safe for people, but further research is underway to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ARGX-119 is unique because it offers a new approach for treating Congenital Myasthenic Syndromes (CMS), a group of genetic disorders that typically affect how signals are transmitted between nerves and muscles. Unlike current treatments like acetylcholinesterase inhibitors, which increase neurotransmitter levels, or immunosuppressants that dampen the immune response, ARGX-119 targets specific pathways involved in muscle function. Researchers are excited because this drug could potentially address the underlying causes of muscle weakness in CMS, offering hope for improved patient outcomes. Additionally, its delivery via intravenous infusion every other week could provide a more manageable regimen for patients compared to daily oral medications.

What evidence suggests that ARGX-119 might be an effective treatment for Congenital Myasthenic Syndromes?

Research has shown that ARGX-119, which participants in this trial may receive, is generally safe and well-tolerated in early studies. This treatment is being explored for conditions like congenital myasthenic syndromes, which affect muscle strength and movement. Although detailed information on its effectiveness for this specific condition is limited, early results suggest that people can take ARGX-119 without major issues. The main focus so far has been on safety, and studies indicate that the body handles it well. More research is needed to understand how it might help improve symptoms. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with a genetic condition called DOK7-Congenital Myasthenic Syndromes. Participants must be at least 18 years old and have been on a stable dose of oral beta agonists, like albuterol or ephedrine, for over three months.

Inclusion Criteria

My condition is confirmed as DOK7-CMS through genetic testing.

I have been on a stable dose of oral beta agonists for over 3 months and will not change it during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusions of ARGX-119 or placebo every other week

42 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ARGX-119

Trial Overview The study tests the safety and effects of ARGX-119 compared to a placebo in treating DOK7-CMS. Patients will receive intravenous infusions and be observed for approximately 11 months to see how their bodies react and if their symptoms improve.

How Is the Trial Designed?

Group I: ARGX-119 Experimental Treatment 1 Intervention

Participants receiving intravenous infusion of ARGX-119 once every other week

Group II: Placebo Placebo Group 1 Intervention

Participants receiving intravenous infusion of placebo once every other week

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

Published Research Related to This Trial

Congenital myasthenic syndromes are genetic disorders affecting neuromuscular transmission that can be present at birth but may not show symptoms until later in life, making them important to consider in diagnosing conditions like seronegative myasthenia gravis.

Diagnostic criteria have been developed that combine clinical features, responses to cholinesterase inhibitors, and electrodiagnostic studies to help identify specific types of congenital myasthenia, such as slow-channel syndrome and acetylcholinesterase deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndromes. Harper, CM.[2005]

In a study of 37 patients from 13 families with congenital myasthenic syndromes linked to chromosome 17p, researchers identified seven mutations in the epsilon-subunit gene of the acetylcholine receptor (AChR), including five novel mutations that lead to low expression or null effects.

These findings suggest that mutations in the AChR epsilon-subunit gene are a prevalent cause of congenital myasthenic syndromes, particularly in eastern Mediterranean populations, highlighting the importance of genetic testing for diagnosis and potential treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chromosome 17p-linked myasthenias stem from defects in the acetylcholine receptor epsilon-subunit gene. Middleton, L., Ohno, K., Christodoulou, K., et al.[2019]

In a study of 22 patients previously diagnosed with 'double' seronegative myasthenia gravis (SNMG), one case of congenital myasthenic syndrome (CMS) was identified, highlighting the potential for misdiagnosis between these conditions.

The research estimated that 4.5% of patients diagnosed with 'double' SNMG may actually have CMS due to mutations in the CHRNE gene, suggesting that genetic screening could improve diagnostic accuracy in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndrome in a cohort of patients with 'double' seronegative myasthenia gravis. Lorenzoni, PJ., Ducci, RD., Arndt, RC., et al.[2023]

Recent advancements have identified genes responsible for about 50% of congenital myasthenic syndrome cases, enhancing our understanding of the disease's genetic basis and classification.

Therapeutic strategies have evolved due to increased knowledge of the mechanisms affecting neuromuscular transmission, leading to improved management of these often under-diagnosed conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current status of congenital myasthenic syndromes]. Bestue-Cardiel, M., Natera-de Benito, D.[2018]

Congenital myasthenic syndromes (CMS) are linked to mutations in various genes affecting neuromuscular junction function, with 15 genes identified in 12 patients diagnosed in Japan, indicating a potential for many undiagnosed cases.

A promising therapeutic approach involves using an AChE/ColQ complex to target and localize treatment specifically to the neuromuscular junction, which could benefit a range of CMS caused by extracellular matrix defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Congenital myasthenic syndromes]. Ohno, K.[2019]

A fatal congenital myasthenic syndrome was linked to a homozygous c.340delA mutation in the synaptobrevin 1 (SYB1) gene, which is crucial for synaptic vesicle exocytosis, indicating a presynaptic defect in muscle action potential transmission.

The mutation causes elongation of the C-terminus of SYB1 isoforms, which increases the energy needed for synaptic vesicle fusion, thereby impairing neurotransmitter release and contributing to the disease's pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel synaptobrevin-1 mutation causes fatal congenital myasthenic syndrome. Shen, XM., Scola, RH., Lorenzoni, PJ., et al.[2019]

In a rare case of congenital myasthenic syndrome caused by mutations in the CHRNE and COLQ genes, traditional treatment with neostigmine was ineffective, highlighting the limitations of anticholinesterase inhibitors for this condition.

The patient showed significant improvement when treated with oral salbutamol, suggesting that this medication may be a promising alternative therapy for certain variants of congenital myasthenic syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndrome: a tale of two siblings. Banerjee, A., Datta Kanjilal, S., Biswas, T., et al.[2022]

In a study of eight patients with Congenital Myasthenic Syndromes (CMS) in Turkey, mutations in the CHRNE and COLQ genes were identified, highlighting the genetic basis of these disorders and their prevalence in this population.

Treatment options, including pyridostigmine for AChR deficiency and beta adrenergic agonists for COLQ mutations, can lead to significant recovery, emphasizing the importance of genetic testing for personalized therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndrome in Turkey: clinical and genetic features in the long-term follow-up of patients. Gül Mert, G., Özcan, N., Hergüner, Ö., et al.[2021]

In a study of 35 Chinese patients with congenital myasthenic syndrome, distinct genetic mutations were identified, with GFPT1 and AGRN being the most common, indicating a unique genetic distribution compared to other populations.

Therapeutic responses varied significantly among different genetic subtypes, with acetylcholinesterase inhibitors showing limited effectiveness in COLQ mutations and variable responses in AGRN mutations, while albuterol was generally effective, though long-term use may reduce efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndrome in China: genetic and myopathological characterization. Zhao, Y., Li, Y., Bian, Y., et al.[2022]

In a study of 34 adults diagnosed with congenital myasthenic syndromes (CMS), 94% were misdiagnosed, often as seronegative myasthenia gravis or muscle diseases, leading to a median diagnostic delay of 26 years from symptom onset.

The majority of patients (30 out of 34) received a molecular diagnosis, highlighting the importance of genetic testing in accurately diagnosing CMS and avoiding unnecessary treatments like immunotherapy or thymectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndromes in adult neurology clinic: A long road to diagnosis and therapy. Kao, JC., Milone, M., Selcen, D., et al.[2019]

Citations

1. argenx.com argenx.com/news/2025/press-release-3107132

argenx Advances Clinical Development of ARGX-119 in ... ARGX-119 demonstrated a favorable safety and tolerability profile, which was the primary endpoint. Efficacy was evaluated across multiple ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06436742

NCT06436742 | A Phase 1b Study to Investigate Safety ... The purpose of this study is to assess the safety and tolerability of ARGX-119 in adult participants with DOK7- Congenital Myasthenic Syndromes. The study will ...

3. ddw-online.com ddw-online.com/argenx-advances-argx-119-in-congenital-myasthenic-syndromes-35552-202507/

argenx advances ARGX-119 in congenital myasthenic ... The decision follows the analysis of topline data from the Phase Ib study, in which ARGX-119 demonstrated a favourable safety and tolerability ...

4. argenxmedical.com argenxmedical.com/content/dam/medical-affairs/congress-posters/nuerology/aanem-2024/Safety,%20Tolerability,%20Pharmacokinetics,%20Immunogenicity,%20and%20Efficacy%20of%20ARGX-119%20in%20Participants%20With%20DOK7%20Congenital%20Myasthenic%20Syndromes%20Phase.pdf

Phase 1b Study in Progress Congenital Myasthenic Syndromes (CMS). • CMS are a rare, heterogeneous group of congenital disorders caused by impaired neuromuscular transmission and.

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000212107

First-in-Human Dose Selection and Pharmacokinetics ... Preliminary results from the FIH study suggest that ARGX-119 has a favorable safety profile in healthy participants at the doses investigated.