Treatment of Myasthenia Gravis Exacerbation or Crisis With Efgartigimod

Phase 4

Not yet recruiting

• Conditions: Myasthenia Gravis Crisis; Myasthenia Gravis Exacerbations; AChR Myasthenia Gravis
• Interventions: Drug: Efgartigimod

• Registration Number: NCT06860633
• Lead Sponsor: University of Colorado, Denver

Brief Summary

This study plans to learn more about if the drug efgartigimod can be used in the hospital to treat exacerbations in participants with myasthenia gravis (MG). Efgartigimod has been approved by the FDA for ongoing (chronic) treatment of generalized MG in adult patients who are anti-acetylcholine receptor (AChR) antibody positive but has not been studied in the treatment of worsening weakness requiring hospital admission (known as "exacerbation"). This investigation aims to see if using efgartigimod in this way improves symptoms and recovery from exacerbation, and how it affects certain MG markers in the blood. The main questions it aims to answer are:

* Is efgartigimod effective as a hospital-administered acute therapy for participants with worsening MG (MG exacerbation) who require hospitalization?

* Will efgartigimod lead to clinical improvement with a similar reduction in validated research scales, such as the Quantitative MG (QMG) scale, as standard of care therapies?

Participants will receive 4 doses of efgartigimod over the course of 4 weeks with an additional follow-up visit at the clinic.

Detailed Description

Efgartigimod is thought to work by reducing circulating IgG antibodies, including the antibodies that cause MG. One of the currently used treatments for MG exacerbation, called plasma exchange (PLEX), is also thought to work by reducing antibody levels by filtering blood through a machine similar to those used in dialysis for kidney failure. Because of the similarities between how these two treatments work, there is reason to believe that efgartigimod may also be helpful in treating MG exacerbation.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-28
• Study First Submitted QC: 2025-02-28
• Last Update Submitted: 2025-02-28
• Study First Posted: 2025-03-06
• Last Update Posted: 2025-03-06
• Study Start: 2025-03-15
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Adults ≥ age 18 years with known generalized MG as identified by characteristic signs of generalized MG on clinical assessment and positive serology for AchR antibodies as well as one of the following:

  1. Documented positive response to cholinesterase inhibitors such as pyridostigmine or edrophonium
  2. Abnormal decrement on slow repetitive nerve stimulation testing
  3. Abnormal single fiber EMG

• Evidence of worsening weakness requiring hospital admission for stabilization and change in therapy as determined by a neuromuscular expert including:

  1. Quantitative Myasthenia Gravis (QMG) scale ≥ 11
  2. MG-ADL score ≥ 6
  3. Worsening weakness that is unlikely to be ameliorated by adjustment of current medications including impaired respiratory status, dysarthria, dysphagia, difficulty chewing, limb weakness, diplopia, ptosis.

• Ability to sign consent and be enrolled within 24 hours of hospital admission. For participants transferred to University of Colorado Hospital, the time of admission/presentation to the outside hospital is counted towards this 24-hour cap.

Exclusion Criteria

• MG worsening thought to be related to active infection or due to medications (e.g. fluoroquinolone or aminoglycoside antibiotics, magnesium, chloroquine derivatives)
• Intubation prior to ability to sign informed consent or intubation within 24 hours of hospitalization
• Use of IVIG within 2 weeks, or having undergone plasma exchange or received efgartigimod in the 4 weeks prior to admission
• Current ongoing use of ravulizumab or eculizumab (monoclonal antibody C5-complement inhibitors).
• Other medical conditions that, in the opinion of the investigator and treating clinicians, might interfere with the validity of assessment measures used in the study (e.g. steroid myopathy, CNS pathology, severe arthritis, fractures, etc.). This criterion is a standard exclusion in MG trials and relates solely to other conditions that reduce muscle power or range of motion and would thus worsen scores on assessment measures like the QMG due to non-MG conditions.
• Known history of coagulopathy, blood clotting, recent severe bleeding (e.g. GI bleed).
• Pregnancy or breastfeeding. Pregnancy must be excluded for all potential participants who are able to become pregnant prior to initiation of treatment.
• IgG levels < 600mg/dL
• Evidence of active or chronic Hepatitis B infection, untreated Hepatitis C infection, HIV with low CD4 (<200) count.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Efgartigimod	Efgartigimod	Participants receive 4 doses of efgartigimod via intravenous (IV) infusion over the course of the study on days 1, 4, 11 and 18.

Primary Outcome Measures

Name	Time	Method
Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 11	Baseline, Day 11	The Quantitative Myasthenia Gravis (QMG) is a scoring system that quantifies disease severity by measuring ocular, bulbar, respiratory and limb strength. The total scores range from 0 to 39, with higher scores indicating greater disease severity.

Secondary Outcome Measures

Name	Time	Method
Percentage of participants requiring rescue therapy with Plasma Exchange (PLEX) or Intravenous Immunoglobulin (IVIG)	During hospitalization, approximately 7 days	Number of participants requiring rescue therapy with Plasma Exchange (PLEX) or Intravenous Immunoglobulin (IVIG) over number of total participants
Change from baseline in Myasthenia Gravis Activities of Daily Life (MG-ADL) scale at day 18	Baseline, Day 18	The Myasthenia Gravis Activities of Daily Life (MG-ADL) is a questionnaire administered verbally that measures MG symptoms and functional activities related to activities of daily living. The summative total scores range from 0 to 24, with higher scores indicating greater disease severity.
Change from baseline in Myasthenia Gravis Activities of Daily Life (MG-ADL) scale at day 32	Baseline, Day 32	The Myasthenia Gravis Activities of Daily Life (MG-ADL) is a questionnaire administered verbally that measures MG symptoms and functional activities related to activities of daily living. The summative total scores range from 0 to 24, with higher scores indicating greater disease severity.
Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at day 32	Baseline, Day 32	The Myasthenia Gravis Manual Muscle Test (MG-MMT) is an assessment that assigns numerical values to the presence of mild, moderate or severe weakness for specific muscle groups that may be affected by MG. The summative total scores range from 0 to 120, with higher scores indicating greater disease severity.
Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at day 11	Baseline, Day 11	The Myasthenia Gravis Manual Muscle Test (MG-MMT) is an assessment that assigns numerical values to the presence of mild, moderate or severe weakness for specific muscle groups that may be affected by MG. The summative total scores range from 0 to 120, with higher scores indicating greater disease severity.
Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at day 18	Baseline, Day 18	The Myasthenia Gravis Manual Muscle Test (MG-MMT) is an assessment that assigns numerical values to the presence of mild, moderate or severe weakness for specific muscle groups that may be affected by MG. The summative total scores range from 0 to 120, with higher scores indicating greater disease severity.
Change from baseline in Myasthenia Gravis Quality of Life-15 Revised (MG-QOL15r) at day 18	Baseline, Day 18	The Myasthenia Gravis Quality of Life-15 Revised (MG-QOL15r) is a scale that measures perceived limitations to fifteen different activities due to MG. Individual items are score 0 (not at all) to 4 (quite a bit). The summative total scores range from 0 to 60, with higher scores representing worse quality of life.
Change from baseline in Myasthenia Gravis Quality of Life-15 Revised (MG-QOL15r) at day 32	Baseline, Day 32	The Myasthenia Gravis Quality of Life-15 Revised (MG-QOL15r) is a scale that measures perceived limitations to fifteen different activities due to MG. Individual items are score 0 (not at all) to 4 (quite a bit). The summative total scores range from 0 to 60, with higher scores representing worse quality of life.
Postinterventional status at day 32	Day 32	Postinterventional status is an assessment of whether a participants's MG symptoms/signs have remained unchanged, worsened, improved or reached minimal manifestations or minimal symptom expression.
Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 4	Baseline, Day 4	The Quantitative Myasthenia Gravis (QMG) is a scoring system that quantifies disease severity by measuring ocular, bulbar, respiratory and limb strength. The total scores range from 0 to 39, with higher scores indicating greater disease severity.
Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 32	Baseline, Day 32	The Quantitative Myasthenia Gravis (QMG) is a scoring system that quantifies disease severity by measuring ocular, bulbar, respiratory and limb strength. The total scores range from 0 to 39, with higher scores indicating greater disease severity.
Postinterventional status at day 11	Day 11	Postinterventional status is an assessment of whether a participant's MG symptoms/signs have remained unchanged, worsened, improved or reached minimal manifestations or minimal symptom expression.
Postinterventional status at day 18	Day 18	Postinterventional status is an assessment of whether a participant's MG symptoms/signs have remained unchanged, worsened, improved or reached minimal manifestations or minimal symptom expression.
Length of hospital stay	Duration of hospitalization, approximately 7 days	Length of time between the participant being admitted to discharged. For participants transferred to University of Colorado Hospital, the time of admission/presentation to the outside hospital is counted.
Proportion of participants requiring mechanical ventilation	During hospitalization, approximately 7 days	Number of participants requiring mechanical ventilation against the total number of participants.
Proportion of participants requiring enteral feeding	During hospitalization, approximately 7 days	Number of participants requiring enteral feeding (such as an NG tube or PEG tube) against the total number of participants.
Time to freedom from respiratory support	During hospitalization, approximately 7 days	Length of time between the participant being put on respiratory support (e.g. ventilator, BiPAP) and respiratory support being discontinued.
Change from baseline in Total Immunoglobin G (IgG) at day 32	Baseline, Day 32	Immunoglobin G (IgG) total level will be measured via blood collection.
Change from baseline in Acetylcholine Receptor (AchR) antibody titer at day 32	Baseline, Day 32	Acetylcholine Receptor (AchR) antibody titer will be measured via blood collection.

Trial Locations

Locations (1)

University of Colorado; 🇺🇸 Aurora, Colorado, United States