Evaluation of the Condition of Patients Receiving EARLY Ravulizumab and Admitted in ICU for gMG Crisis

Официальное название

Evaluation of the Condition of Patients Receiving EARLY Treatment With Ravulizumab and Admitted in ICU for Generalized Myasthenia Gravis (gMG) Crisis : an Observational Prospective Multicentric Study in France

Обзор

Myasthenia Gravis (MG) is a rare autoimmune disease that causes muscle weakness and fatigue. It occurs when the immune system produces antibodies that block communication between nerves and muscles. In some patients, the disease can suddenly worsen and cause severe breathing problems. This life-threatening situation is called a myasthenic crisis and requires immediate treatment in an intensive care unit (ICU). During such crises, patients may need to receive respiratory assistance through a ventilator. These episodes are often long and can lead to complications such as infections or heart problems. To manage a myasthenic crisis, doctors usually use treatments that remove or neutralize the harmful antibodies: plasma exchange (PLEX) or intravenous immunoglobulin (IVIg). Although both are effective, recovery can be slow, and many patients remain in the ICU for several weeks. Ravulizumab (Ultomiris®) is a new medicine that targets a specific part of the immune system called the complement system, which contributes to muscle damage in MG. It is already approved for adults with generalized MG who have anti-acetylcholine receptor (AChR) antibodies. Ravulizumab is given by intravenous infusion every eight weeks. Clinical studies have shown that it can improve symptoms within one week of starting treatment. Some doctors have started using ravulizumab early, after PLEX or IVIg, for patients hospitalized in the ICU for a myasthenic crisis. Early use of this treatment could help reduce the duration and severity of the crisis, leading to faster recovery and shorter hospital stays. However, there is currently no national study that systematically collects data on this approach. The EARLY-MG study aims to describe the condition and recovery of patients who receive ravulizumab early during a myasthenic crisis requiring ICU admission. The study will not test an experimental treatment or change medical care. It is an observational study. The main hypothesis of the study is that early administration of ravulizumab, after PLEX or IVIg, may help patients recover faster, improve muscle strength, and reduce complications and hospital stay. Around 30 adult patients with generalized MG and anti-AChR antibodies will be enrolled in 10 centers across France. Each patient will be followed for 26 weeks (about six months). Assessments will be performed at the start of the study and at weeks 2, 4, 10, 18, and 26. Investigators will collect information such as: * Duration of stay in the ICU and in the hospital after receiving ravulizumab * Duration of mechanical ventilation, if needed * Clinical improvement using standard evaluation scales (Myasthenia Gravis Activities of Daily Living, MG Foundation of America classification, and Garches' score) * Occurrence of any complications or additional treatments The study will last about 18 months in total, including one year for patient inclusion and six months of follow-up per patient. The results may help guide future recommendations and improve patient care in France and worldwide.

Вмешательства

• Другое early use of Ravulizumab
  early use of Ravulizumab after PLEX or IVIg for a MG crisis in previously treated anti-AChR antibody-positive (anti-AChR-Ab+) patients with gMG

Первичные конечные точки

• Short-term change in clinical outcomes [Срок оценки: Week 0, 2, 4 and 10]
• Short-term change in clinical outcomes [Срок оценки: Week 0, 2, 4 and 10]
• Short-term change in clinical outcomes [Срок оценки: Week 0, 2, 4 and 10]

Вторичные конечные точки (11)

• Long term change in clinical outcomes 1 [Срок оценки: Week 18 and 26]
• Long term change in clinical outcomes 2 [Срок оценки: Week 18 and 26]
• Long term change in clinical outcomes 3 [Срок оценки: Week 18 and 26]
• Time to observe a clinical improvement [Срок оценки: From the day the patient begin the study to the first day the patient reach the Myasthenia Gravis Foundation of America III category - in days, up to 180 days]
• Time in days from Ravulizumab administration to the day of ICU discharge [Срок оценки: From the day the patient begin the Ravulizumab administration to the day the patient leaves ICU - in days, up to 180 days]
• Total Length Of Stay at the hospital after Ravulizumab administration [Срок оценки: From the day the patient begin the Ravulizumab administration to the day the patient leaves the hospital - in days, up to 180]
• Duration of ventilation after ravulizumab administration [Срок оценки: From the day the patient begin the Ravulizumab administration to the day the patient leaves ICU - in days, up to 180 days]
• Patient's condition [Срок оценки: Ongoing from ICF signing to the end of the study]
• Patient's condition [Срок оценки: Ongoing from ICF signing to the end of the study]
• Patient's condition [Срок оценки: Ongoing from ICF signing to the end of the study]
• Patient's condition [Срок оценки: Ongoing from ICF signing to the end of the study]

Критерии участия

Критерии включения

• Male or female aged ≥18 years.
• Diagnosed with gMG with confirmed documentation and supported by a physical exam and confirmed seropositivity for AChR-Abs.
• Patients having received more than 1 cycle of PLEX or IVIg 1-2 g/kg (max 50g/day), according to clinical practice.
• Meets the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MFGA) for generalized MG class V - IV, at ICU admission.
• Patients treated with at least one standard MG-targeted therapy.
• Patients receiving Ravulizumab following PLEX of IVIg during their stay in the ICU, as per local label and reimbursement conditions. The prescription must be validated by experts from the French Health Care Network for rare neuromuscular diseases FILNEMUS.
• Patients capable of understanding written informed consent and providing signed, dated, and witnessed written informed consent. If unable to sign the consent due to muscular weakness, a dedicated informed consent can be signed by a trusted witness.
• Patients willing and able to comply with scheduled visits, treatment plan, study restrictions and other study procedures.
• Patients affiliated to a European social security system.
• Patients agree to comply with the prevention of meningococcal infections by vaccination and/or antibiotic prophylaxis in accordance with the current local vaccination/antibiotic prophylaxis recommendations.
• Patients with no contraindication to anti-C5 treatment.
• Patients with no contraindication to antibiotic therapy.

Критерии исключения

• Active infection or other disorders causing weakness, known immunoglobulin A deficiency, active renal or hepatic disease, clinically significant cardiac disease, known hyperviscosity, or hypercoagulable state.
• Any active malignancy.
• Presence of antibodies other than anti-AChR-Ab+ (anti-titin-Ab+ were permitted as these are considered complementary markers to anti-AChR-Ab+).
• Patient with a diagnosed thymoma.
• Patient with a pathology judged by the investigator to interfere with the proper conduct of the study.
• Positive pregnancy test. A urine pregnancy test will be carried out for women of childbearing age.
• Any current mental condition (psychiatric disorder, senility, or dementia) that, in the opinion of the investigator, may affect study compliance or prevent understanding of the aims, investigational procedures, or possible consequences of the study.
• Vaccination with live or live-attenuated vaccines within the 6 weeks.
• Refusal of the subject to participate in the study.
• Patient protected by law, under guardianship or curator ship, or not able to participate in a clinical study according to the article L.1121-16 of the French Public Health Code.
• Known hypersensitivity to the active substance or to any of the excipients.

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• CHU de NICE — Nice

Идентификаторы

NCT: NCT07411963 · 25-PP-09

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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