Efgartigimod treatment for seronegative myasthenia gravis

Efficacy, Safety and Tolerability of Efgartigimod in Patients with Seronegative Generalized Myasthenia Gravis: an Open-Label Study

This study is testing a new treatment called efgartigimod to see if it can help people with seronegative myasthenia gravis feel better and manage their symptoms.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Drugs / interventions: rituximab, eculizumab, immunotherapy, methotrexate
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06587867 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy, safety, and tolerability of efgartigimod in patients diagnosed with seronegative generalized myasthenia gravis. The study involves a screening period followed by a run-in phase, an induction phase with weekly treatments, and a maintenance phase with bi-weekly treatments, culminating in a total duration of 43 weeks. Participants will undergo various assessments including ECGs, blood tests, and neuromuscular transmission tests to ensure eligibility and monitor progress throughout the study.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with a confirmed diagnosis of seronegative generalized myasthenia gravis and limited response to existing treatments.

Not a fit: Patients who do not have seronegative generalized myasthenia gravis or those who have not responded to immunotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of seronegative generalized myasthenia gravis, offering new hope for patients with limited response to current therapies.

How similar studies have performed: Other studies have shown promise with similar treatments for myasthenia gravis, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

* Evidence of signed and dated informed consent document(s) indicating that the subject has been informed of all pertinent aspects of the trial. Subjects must be willing and able to comply with the protocol, complete study assessments, and return for follow-up visits.
* Male or female subjects ≥ 18 years old.
* Diagnosis of SN MG defined as: (a) clinical syndrome consistent with a diagnosis of MG, and not otherwise explained by another condition, (b) abnormal neuromuscular transmission test results demonstrated by single-fiber electromyography or repetitive nerve stimulation; and (c) negative serologic test for anti-AChR and anti- MuSK antibodies as confirmed at screening, (d) limited, if any, response to therapy with immunotherapy and/or antiacetylcholinesterase (AChE) treatment. Further testing for low affinity antibodies to rapsyn-clustered AChR by cell-based assays will be done at baseline and the results included as part of subgroup analysis. All patients will have a negative genetic test for congenital myasthenic syndromes by history or at baseline to exclude the possibility of congenital myasthenic syndrome mimicking SN MG.
* MGFA Clinical Classification Class II, III, or IV at the time of screening and baseline.
* Moderate to severe myasthenia gravis as defined by a generalized myasthenia gravis impairment index score \> 11 or MG-ADL score of at least 5 (with \>50% of the score due to non-ocular symptoms) and a PASS response of "No" and a SSQ of \< 70% with at least 6 months of historical data as the baseline.
* Stable or worsening MG as defined by MGII remaining stable or increasing in the 4 week run-in interval.
* Patients are required to be on a stable dose of their MG treatment (Standard of care-SoC) for at least one month prior to screening. The SoC is limited to AChE inhibitors, steroids and NSISTs (e.g., azathioprine, methotrexate, cyclosporine, tacrolimus, and mycophenolate mofetil. There is no requirement for specific generalised myasthenia gravis therapies.
* Patients who discontinued early from previous trials of efgartigimod for reasons other than pregnancy, rescue therapy or a SAE can be included.
* Females of childbearing potential who are sexually active with a non-sterilized male partner must be willing to use at least one highly effective contraception method from the time of screening and for 3 months after the final dose of efgartigimod.
* Non-sterilized males who are sexually active with a female partner of childbearing potential must be willing to use a condom for the duration of the study and for 3 months after the last dose of efgartigimod. Because male condom is not a highly effective contraception method, it is strongly recommended that female partners of a male study subject also use a highly effective method of contraception throughout this period.
* Vital signs, electrocardiogram (ECG), and laboratory parameters within the normal ranges at screening, or, if outside normal ranges, deemed not clinically significant by the Investigator.
* Patient has documented IgG \>6 g/L within one month of screening
* Vaccinated for COVID-19 at least 2 weeks prior to screening visit.

Exclusion Criteria:

* Patients who discontinued early from trials of efgartigimod for pregnancy or rescue reasons or an SAE that was likely to result in a life-threatening situation or pose a serious safety risk.
* Pregnant and lactating women, and those intending to become pregnant during the trial or within 3 months after the last dosing. Women of childbearing potential should have a negative urine pregnancy test at screening and baseline.
* Male patients who are sexually active and do not intend to use effective methods of contraception (as mentioned above) during the trial or within 3 months after the last dosing or male patients who plan to donate sperm during the trial or within 3 months after the last dosing.
* Patients with known hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) seropositivity.
* Patients with known autoimmune disease other than MG (e.g., rheumatoid arthritis) which in the investigator opinion would interfere with an accurate assessment of clinical symptoms.
* Patients with clinical evidence of other significant disease or patients who underwent a recent major surgery, which could confound the results of the trial or put the patient at undue risk.
* Patients with renal/hepatic function impairment as defined by (Cr\>1.5 x elevated) and/or (transaminases \> 2.5 x elevation) at screening.
* Patients with known medical history of hypersensitivity to any of the ingredients of efgartigimod.
* Patients who have received rituximab or eculizumab in the 6 months before screening.
* Patients who have undergone thymectomy within 3 months of screening.
* Patients who had intravenous immunoglobulin or plasma exchange within 4 weeks of screening.
* Patient who has clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening
* Patient has received a live or a live-attenuated vaccination during the month before screening

Where this trial is running

Toronto, Ontario

• University Health Network, Division of Neurology, Toronto General Hospital — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Vera Bril, MD — Toronto General Hospital
• Study coordinator: Eduardo Ng

Conditions Efgartigimod; Generalized Myasthenia Gravis; seronegative; generalized myasthenia gravis