Efgartigimod in IVIG Dependent Myasthenia Gravis Patients

Обзор

This study is an open label, single center, prospective, 26 weeks study with descriptive analysis where IVIG is replaced by efgartigimod therapy. MG-ADL and MGQOL evaluations will occur weekly throughout the study to week 26.

Подробное описание

Objectives:

To determine if efgartigimod is equivalent or non-inferior in efficacy to IVIG in the treatment of stable, acetylcholine receptor antibody positive, IVIG dependent myasthenia gravis patients.

To determine patient treatment preference between IVIG and efgartigimod in stable, IVIG dependent acetylcholine receptor antibody positive myasthenia gravis patients.

To determine the safety and tolerability of efgartigimod administered in a fixed regular dosing regimen over 6 months in stable IVIG dependent acetylcholine receptor antibody positive myasthenia gravis patients.

IVIG will be discontinued one week prior to the baseline visit (week 0) while other concurrent medications (non-steroidal immunosuppressive therapies (NSISTs), acetylcholinesterase (AChE) inhibitors or corticosteroids) for myasthenia will be kept unchanged for the duration of the study. The dose and frequency of efgartigimod treatment will be 10mg/kg (max of 1200mg) administered as a one-hour intravenous infusion every week x 4 infusions followed by a four-week break and repeated for a total four treatment cycles till week 24 and then followed by a two-week observation with an end of study visit at week 26.

Вмешательства

• Препарат efgartigimod administration
  efgartigimod infusion

Первичные конечные точки

• MG-ADL [Срок оценки: a sustained decrease persistent for at least 4 consecutive weeks over the 26 week period]

Вторичные конечные точки (3)

• QMG [Срок оценки: those who experience a sustained decrease for 4 consecutive weeks during the 26 week period]
• MGQOL [Срок оценки: during the whole study period of 26 weeks]
• incidence of patients who are still receiving efgartigimod by the end of the 26 weeks [Срок оценки: for the duration of the 26 week study]

Критерии участия

Критерии включения

• 1\. Signed informed consent. 2. Age 18-80 years 3. Acetylcholine receptor antibody positive, myasthenia gravis patients, with stable disease for the past four or more months. Stable disease is defined as no change in dosage or interval in IVIG treatments and without any significant change in clinical status.

4\. No modification or addition of NSISTs in the past six months 5. No modification or addition in corticosteroid therapy for the past three months 6. Myasthenia Gravis diagnosis was supported by abnormal neurotransmission test or history of improvement with AChE inhibitors.

7\. Receiving chronic regular IVIG treatments for myasthenia gravis for the past year or more.

Критерии исключения

• 1\. Patients with previous rituxan or eculizumab treatment or plasma exchange within the past six months 2. Patients with previous thymectomy within the past 3months 3. Patients that have active Hepatitis B, are seropositive for Hepatitis C or HIV or have latent, untreated or active TB or any other significant active infection 4. Patients that have at screening a serum IgG less than 6.0gm/L or a history of chronic hypogammaglobulinemia from any cause.

5\. Patients that are pregnant or considering becoming pregnant in the next 6 months.

6\. Patients with severe renal impairment (eGFR less than 30ml/min) 7. Patients who in the opinion of the investigator should not participate in the study.

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

Канада · 1 центр

• Clinique Neuro-Outaouais — Gatineau

Публикации

• Burns TM, Sadjadi R, Utsugisawa K, Gwathmey KG, Joshi A, Jones S, Bril V, Barnett C, Guptill JT, Sanders DB, Hobson-Webb L, Juel VC, Massey J, Gable KL, Silvestri NJ, Wolfe G, Cutter G, Nagane Y, Murai H, Masuda M, Farrugia ME, Carmichael C, Birnbaum S, Hogrel JY, Nafissi S, Fatehi F, Ou C, Liu W, Conaway M. International clinimetric evaluation of the MG-QOL15, resulting in slight revision and sub PMID 27220659
• Barnett C, Katzberg H, Nabavi M, Bril V. The quantitative myasthenia gravis score: comparison with clinical, electrophysiological, and laboratory markers. J Clin Neuromuscul Dis. 2012 Jun;13(4):201-5. doi: 10.1097/CND.0b013e31824619d5. PMID 22622164
• Howard JF Jr, Bril V, Vu T, Karam C, Peric S, De Bleecker JL, Murai H, Meisel A, Beydoun SR, Pasnoor M, Guglietta A, Van Hoorick B, Steeland S, T'joen C, Utsugisawa K, Verschuuren J, Mantegazza R; ADAPT+ Study Group. Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis. Fr PMID 38318236
• Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology. 1999 Apr 22;52(7):1487-9. doi: 10.1212/wnl.52.7.1487. PMID 10227640
• Howard JF Jr, Bril V, Vu T, Karam C, Peric S, Margania T, Murai H, Bilinska M, Shakarishvili R, Smilowski M, Guglietta A, Ulrichts P, Vangeneugden T, Utsugisawa K, Verschuuren J, Mantegazza R; ADAPT Investigator Study Group. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet PMID 34146511
• Sesarman A, Vidarsson G, Sitaru C. The neonatal Fc receptor as therapeutic target in IgG-mediated autoimmune diseases. Cell Mol Life Sci. 2010 Aug;67(15):2533-50. doi: 10.1007/s00018-010-0318-6. Epub 2010 Mar 9. PMID 20217455

Идентификаторы

NCT: NCT06765161 · ESR-CA-NEU-96

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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