Clinical trial NCT06599697: The MIGHT Trial - An Exploratory Clinical Trial of IVIG in Anti-HMGCR Immune Mediated Necrotizing Myopathy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Anti-3-hydroxy-3-methylglutaryl-CoA Reductase (HMGCR) Immune-Mediated Necrotizing Myopathy
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2024-09-19
Enrollment: 12
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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. Enrolled participants will be randomized 1:1 to receive either IVIG 2g/kg or placebo (0.9% sodium chloride at equivalent volume) at weeks 0, 4, and 8. The 2g/kg q4 weeks regimen of IVIG was chosen based on the investigators' clinical experience and prior studies. The primary endpoints will be assessed at week 12. After the randomized phase of the trial, all participants, except those who were randomized to IVIG and met the clinical deterioration criteria, will be offered an open-label extension to receive IVIG at weeks 12, 16, and 20.
Primary purpose: TREATMENT

Brief summary: 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, except those who were randomized to IVIG and met the clinical deterioration criteria, 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.


Eligibility criteria: Inclusion Criteria:

* 16 years of age or older
* Anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody positive
* Serum creatine kinase \> 5x upper limit of normal
* Anti-HMGCR Immune Mediated Necrotizing Myopathy (IMNM) disease duration \< 36 months at screening
* No moderate or severe respiratory or swallowing dysfunction due to Immune Mediated Necrotizing Myopathy at screening
* No history of dermatomyositis rash

Exclusion Criteria:

* Oral glucocorticoid daily dose \> 15mg at screening
* Change in oral glucocorticoid dose \< 2 weeks prior to screening
* Prior IVIG treatment for anti-HMGCR Immune Mediated Necrotizing Myopathy
* \> 1 oral conventional synthetic disease-modifying antirheumatic drug (DMARD) (e.g., methotrexate, mycophenolate mofetil, azathioprine) use at screening
* Change in concomitant DMARD dose \< 4 weeks prior to screening
* Rituximab treatment within 6 months prior to screening
* Plasma exchange, cyclophosphamide, or biologic immunosuppressive medication within 3 months prior to screening
* Use of statin medication at screening
* History of anaphylactic reaction to intravenous immunoglobulin (IVIG)
* History of angina pectoris, myocardial infarction, transient ischemic attack, or stroke within 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 Pulmonary Embolism score of 4 or more at screening
* Wells' Criteria for Deep Vein Thrombosis score of 2 or more at 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

Primary outcomes:
measure: Percentage change in serum creatine kinase (CK)
timeFrame: Week 0 to 12
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: James Andrews, MD
role: PRINCIPAL_INVESTIGATOR
References: