Treatment of Myasthenia Gravis Exacerbation or Crisis With Efgartigimod

Официальное название

Treatment of Myasthenia Gravis Exacerbation or Crisis With Efgartigimod: A Single Arm, Open Label Prospective Cohort Study

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Efgartigimod
  Dose of 10 mg/kg for IV infusion on days 1, 4, 11 and 18

Первичные конечные точки

• Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 11 [Срок оценки: Baseline, Day 11]

Вторичные конечные точки (12)

• Percentage of participants requiring rescue therapy with Plasma Exchange (PLEX) or Intravenous Immunoglobulin (IVIG) [Срок оценки: During hospitalization, approximately 7 days]
• Change from baseline in Myasthenia Gravis Activities of Daily Life (MG-ADL) scale at day 18 [Срок оценки: Baseline, Day 18]
• Change from baseline in Myasthenia Gravis Activities of Daily Life (MG-ADL) scale at day 32 [Срок оценки: Baseline, Day 32]
• Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at day 11 [Срок оценки: Baseline, Day 11]
• Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at day 18 [Срок оценки: Baseline, Day 18]
• Change from baseline in Myasthenia Gravis Manual Muscle Test (MG-MMT) at day 32 [Срок оценки: Baseline, Day 32]
• Change from baseline in Myasthenia Gravis Quality of Life-15 Revised (MG-QOL15r) at day 18 [Срок оценки: Baseline, Day 18]
• Change from baseline in Myasthenia Gravis Quality of Life-15 Revised (MG-QOL15r) at day 32 [Срок оценки: Baseline, Day 32]
• Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 4 [Срок оценки: Baseline, Day 4]
• Change from baseline in the Quantitative Myasthenia Gravis (QMG) score at day 32 [Срок оценки: Baseline, Day 32]
• Postinterventional status at day 11 [Срок оценки: Day 11]
• Postinterventional status at day 18 [Срок оценки: Day 18]

Критерии участия

Критерии включения

• 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:

• Documented positive response to cholinesterase inhibitors such as pyridostigmine or edrophonium
• Abnormal decrement on slow repetitive nerve stimulation testing
• Abnormal single fiber EMG
• Evidence of worsening weakness requiring hospital admission for stabilization and change in therapy as determined by a neuromuscular expert including:

• Quantitative Myasthenia Gravis (QMG) scale ≥ 11
• MG-ADL score ≥ 6
• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Colorado — Aurora

Публикации

• Phillips LH 2nd. The epidemiology of myasthenia gravis. Ann N Y Acad Sci. 2003 Sep;998:407-12. doi: 10.1196/annals.1254.053. PMID 14592908
• Schneider-Gold C, Hagenacker T, Melzer N, Ruck T. Understanding the burden of refractory myasthenia gravis. Ther Adv Neurol Disord. 2019 Mar 1;12:1756286419832242. doi: 10.1177/1756286419832242. eCollection 2019. PMID 30854027
• Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016 Dec 29;375(26):2570-2581. doi: 10.1056/NEJMra1602678. No abstract available. PMID 28029925
• Habib AA, Sacks N, Cool C, Durgapal S, Dennen S, Everson K, Hughes T, Hernandez J, Phillips G. Hospitalizations and Mortality From Myasthenia Gravis: Trends From 2 US National Datasets. Neurology. 2024 Jan 23;102(2):e207863. doi: 10.1212/WNL.0000000000207863. Epub 2023 Dec 18. PMID 38165317
• Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD002277. doi: 10.1002/14651858.CD002277.pub4. PMID 23235588
• Ipe TS, Davis AR, Raval JS. Therapeutic Plasma Exchange in Myasthenia Gravis: A Systematic Literature Review and Meta-Analysis of Comparative Evidence. Front Neurol. 2021 Aug 31;12:662856. doi: 10.3389/fneur.2021.662856. eCollection 2021. PMID 34531809
• Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012 Nov 22;367(21):2015-25. doi: 10.1056/NEJMra1009433. No abstract available. PMID 23171098
• Barth D, Nabavi Nouri M, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011 Jun 7;76(23):2017-23. doi: 10.1212/WNL.0b013e31821e5505. Epub 2011 May 11. PMID 21562253

Идентификаторы

NCT: NCT06860633 · 24-0158

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗