Treatment of Myasthenia Gravis Exacerbation or Crisis With Efgartigimod

Phase 4RecruitingNCT06860633

University of Colorado, Denver20 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at 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.

Time frame: Baseline, Day 11

Secondary Outcomes

Percentage of participants requiring rescue therapy with Plasma Exchange (PLEX) or Intravenous Immunoglobulin (IVIG)

Number of participants requiring rescue therapy with Plasma Exchange (PLEX) or Intravenous Immunoglobulin (IVIG) over number of total participants

Time frame: During hospitalization, approximately 7 days

Change from baseline in Myasthenia Gravis Activities of Daily Life (MG-ADL) scale at 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.

Time frame: Baseline, Day 18

Change from baseline in Myasthenia Gravis Activities of Daily Life (MG-ADL) scale at day 32

Time frame: Baseline, Day 32

Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at 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.

Time frame: Baseline, Day 11

Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at day 18

Time frame: Baseline, Day 18

Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at day 32

Time frame: Baseline, Day 32

Change from baseline in Myasthenia Gravis Quality of Life-15 Revised (MG-QOL15r) at 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.

Time frame: Baseline, Day 18

Change from baseline in Myasthenia Gravis Quality of Life-15 Revised (MG-QOL15r) at day 32

Time frame: Baseline, Day 32

Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 4

Time frame: Baseline, Day 4

Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 32

Time frame: Baseline, Day 32

Postinterventional status at 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.

Time frame: Day 11

Postinterventional status at 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.

Time frame: Day 18

Postinterventional status at 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.

Time frame: Day 32

Length of hospital stay

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.

Time frame: Duration of hospitalization, approximately 7 days

Proportion of participants requiring mechanical ventilation

Number of participants requiring mechanical ventilation against the total number of participants.

Time frame: During hospitalization, approximately 7 days

Proportion of participants requiring enteral feeding

Number of participants requiring enteral feeding (such as an NG tube or PEG tube) against the total number of participants.

Time frame: During hospitalization, approximately 7 days

Time to freedom from respiratory support

Length of time between the participant being put on respiratory support (e.g. ventilator, BiPAP) and respiratory support being discontinued.

Time frame: During hospitalization, approximately 7 days

Change from baseline in Total Immunoglobin G (IgG) at day 32

Immunoglobin G (IgG) total level will be measured via blood collection.

Time frame: Baseline, Day 32

Change from baseline in Acetylcholine Receptor (AchR) antibody titer at day 32

Acetylcholine Receptor (AchR) antibody titer will be measured via blood collection.

Time frame: Baseline, Day 32

Treatment of Myasthenia Gravis Exacerbation or Crisis With Efgartigimod

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts