ARGX-119 for Congenital Myasthenic Syndromes

Recruiting at 7 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

16 Participants Needed

Trial Summary

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.

What data supports the idea that ARGX-119 for Congenital Myasthenic Syndromes is an effective treatment?

The available research does not provide specific data on the effectiveness of ARGX-119 for Congenital Myasthenic Syndromes. The articles focus on the challenges of diagnosing and understanding the condition, as well as the genetic and clinical features of the syndrome, but do not mention ARGX-119 or its effectiveness as a treatment. ^{1 2 3 4 5}

What safety data exists for ARGX-119 in treating congenital myasthenic syndromes?

The provided research articles do not contain specific safety data for ARGX-119 or any of its alternative names. They focus on the genetic and clinical characterization of congenital myasthenic syndromes and discuss various treatments, but ARGX-119 is not mentioned. Therefore, no safety data for ARGX-119 is available in these sources. ^{2 5 6 7 8}

Is the drug ARGX-119 a promising treatment for Congenital Myasthenic Syndromes?

Yes, ARGX-119 is a promising drug for Congenital Myasthenic Syndromes because it targets the genetic causes of the disorder, potentially improving symptoms and quality of life for patients. ^{4 5 8 9 10}

What is the purpose of this trial?

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 also assess how ARGX-119 is processed by the body (pharmacokinetics), how the immune system reacts to it (immunogenicity), and how it may improve the way patients feel and function. After the screening period, eligible participants will be randomized in a 4:1 ratio to receive intravenous infusions of ARGX-119 or placebo during the treatment period. Participants will then enter the follow-up period. The full duration of the study is approximately 11 months.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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 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]

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]

References

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

Congenital myasthenic syndromes in adult neurology clinic: A long road to diagnosis and therapy. [2019]

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

Congenital myasthenic syndrome in China: genetic and myopathological characterization. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndrome in a cohort of patients with 'double' seronegative myasthenia gravis. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

[Current status of congenital myasthenic syndromes]. [2018]

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

Congenital myasthenic syndromes. [2005]

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

Chromosome 17p-linked myasthenias stem from defects in the acetylcholine receptor epsilon-subunit gene. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndrome: a tale of two siblings. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Congenital myasthenic syndrome in Turkey: clinical and genetic features in the long-term follow-up of patients. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

[Congenital myasthenic syndromes]. [2019]

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

Novel synaptobrevin-1 mutation causes fatal congenital myasthenic syndrome. [2019]