The MIGHT Trial - An Exploratory Clinical Trial of IVIG in Anti-HMGCR Immune Mediated Necrotizing Myopathy

Официальное название

The MIGHT Trial - An Exploratory Clinical Trial of Intravenous Immunoglobulin (IVIG) in Anti-3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR) Immune Mediated Necrotizing Myopathy (IMNM)

Обзор

This is a randomized, placebo-controlled, double blinded phase 2 exploratory clinical trial of intravenously administered pooled human immunoglobulin (IVIG) in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune mediated necrotizing myopathy (IMNM). Planned enrollment is 12 individuals with active anti-HMGCR IMNM meeting inclusion and exclusion criteria. Assuming 20% drop-out, the investigators anticipate 10 participants will complete all study assessments. Enrolled participants will be randomized 1:1 to either IVIG 2g/kg or placebo (0.9% sodium chloride at equivalent volume) at weeks 0, 4, and 8. The primary efficacy and co-primary safety and tolerability endpoints will be assessed at week 12. After the randomized phase of the trial, all participants will be offered to continue on to an open-label extension phase in which participants will receive IVIG at weeks 12, 16, and 20. Participants will then return at week 24 for a final non-infusion visit to reassess safety, tolerability, and efficacy outcome.

Вмешательства

• Биопрепарат Intravenously administered pooled human immunoglobulin (IVIG)
  IVIG 2g/kg every 4 weeks for 12 weeks (3 doses)

Первичные конечные точки

• Percentage change in serum creatine kinase (CK) [Срок оценки: Week 0 to 12]

Критерии участия

Критерии включения

• Age > 16 years
• Anti-HMGCR antibody positive
• MMT-8 score < 142 (range 0-160)
• Serum CK > 5x upper limit of normal
• Anti-HMGCR IMNM disease duration < 36 months at screening
• No moderate or severe respiratory or swallowing dysfunction due to anti-HMGCR IMNM at screening
• No history of dermatomyositis rash
• Must reside in a state with a participating research site

Критерии исключения

• Oral glucocorticoid (GC) daily dose > 15mg at screening
• Change in oral GC dose < 2 weeks prior to screening
• Prior IVIG treatment for anti-HMGCR IMNM

->1 oral conventional synthetic DMARD (e.g. methotrexate, mycophenolate mofetil, azathioprine) use at screening

• Change in concomitant DMARD dose < 4 weeks prior to screening
• Rituximab < 6 months prior to screening
• Plasma exchange, cyclophosphamide, or biologic immunosuppressive medication < 3 months prior to screening
• Use of statin medication at screening
• History of anaphylactic reaction to IVIG
• History of angina pectoris, myocardial infarction, transient ischemic attack, or stroke < 12 months prior to screening
• Females of child-bearing potential who are pregnant, breastfeeding, or are unwilling to practice a highly effective method of contraception during the study
• Wells Criteria for DVT score of 2 or more at screening
• Wells Criteria for PE score of 4 or more at screening
• Weight >120kg
• History of cancer (excluding non-melanomatous skin cancer) < 5 years prior to screening
• History of pulmonary embolism or deep venous thromboembolism < 3 years prior to screening
• History of hyperviscosity or hypercoagulable state
• Currently receiving anti-coagulation therapy (vitamin K antagonists, non-vitamin K oral anticoagulants \[e.g. dabigatran, rivaroxaban, apixaban\], parenteral anticoagulants \[e.g. fondaparinux\]. Note that oral anti-platelet agents are allowed (e.g. aspirin, clopidogrel, ticlopidine).
• Glomerular filtration rate (GFR) <60mL/min at the time of screening
• Any medical condition which, in the investigator's judgment, makes participation in the clinical trial unadvisable or which would interfere with evaluation of the study treatment.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 5 центров

• University of Alabama at Birmingham — Birmingham
• Johns Hopkins University — Baltimore
• University of Pittsburgh — Pittsburgh
• University of Texas Health Science Center at Houston — Houston
• University of Washington — Seattle

Идентификаторы

NCT: NCT06599697 · 300013467 · 1R21AR083566-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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