NCT06688253

Intravenous Human IgG1 Fc Fragment (Efgartigimod) in Myasthenic Crisis

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: Rambam Health Care Campus · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Efgartigimod in Myasthenic Crisis Background Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, characterized by weakness in skeletal muscles. It is associated with the production of autoantibodies, primarily targeting acetylcholine receptors (AchR), and is often complicated by myasthenic crisis, which can lead to severe respiratory failure. Current treatments primarily involve non-specific immunosuppression, which may not provide rapid relief. Aim This study investigates the therapeutic impact of efgartigimod, an FcRn-targeting Fc fragment, on patients experiencing a myasthenic crisis. We hypothesize that efgartigimod is non-inferior to conventional treatments like intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) in terms of clinical efficacy and safety. Study Rationale Efgartigimod aims to reduce pathogenic IgG autoantibodies implicated in MG by accelerating their degradation. This targeted approach could provide faster symptom relief during acute exacerbations compared to existing therapies. Objectives Primary Objective: To assess the non-inferiority of efgartigimod compared to PLEX and IVIG based on MG-ADL improvements. Secondary Objectives: Evaluate safety, tolerability, length of hospital stay, respiratory parameters, need for additional therapies, and one-year outcomes. Primary Endpoint MG-ADL Improvement: Defined as a ≥3-point improvement post-treatment. The comparison will be made using one-month post-treatment assessments, with follow-ups every three months. Secondary Endpoints Safety and tolerability Length of hospital stay Changes in respiratory function Need for rescue therapy in case of clinical deterioration Sample Size The study will recruit 32 patients (16 historical group and 16 interventional group), calculated to detect significant differences in MG-ADL improvements with a significance level of 0.05 and power of 0.80. Patient Recruitment Patients with a confirmed diagnosis of MG who present to the neurology department will be recruited and randomly assigned to either the efgartigimod treatment group or the historical control group receiving standard care (IVIG/PLEX). Inclusion Criteria Adults \> 18 years Confirmed MG diagnosis with generalized weakness (MGFA class II-V) Positive AchR or MuSK antibodies Evidence of myasthenic crisis Informed consent Exclusion Criteria Contraindications to efgartigimod Significant comorbidities affecting study participation Prior exposure to efgartigimod Ongoing infections or conditions exacerbating MG symptoms Recent major surgery or significant renal/hepatic dysfunction Planned Protocol Administer efgartigimod intravenously at 10 mg/kg weekly for four weeks. Total trial duration: 12 months for enrollment and treatment, followed by a 14-month follow-up.

Detailed description

Study Rationale: The study rationale for investigating the effectiveness of IV efgartigimod in myasthenic crisis hinges on the need for treatments that can provide rapid and targeted relief from the acute exacerbations of MG, which are life-threatening. Current treatments, while potentially effective, can be associated with significant side effects and may not work swiftly enough to address the urgent needs of a myasthenic crisis. Efgartigimod, an FcRn antagonist, has been designed to reduce the circulating levels of pathogenic IgG autoantibodies, which are implicated in the pathophysiology of MG. By accelerating the degradation of these autoantibodies, efgartigimod could potentially offer a faster onset of action and improve clinical outcomes in patients during a myasthenic crisis

Conditions

• Myasthenia Gravis Crisis

Interventions

Type	Name	Description
DRUG	IV efgartigimod	IV efgartigimod

Timeline

• Start date: 2024-11-15
• Primary completion: 2025-01-15
• Completion: 2025-03-30
• First posted: 2024-11-14
• Last updated: 2024-11-14

Locations

1 site across 1 country: Israel

Regulatory

• FDA-regulated drug study