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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Anti-3-hydroxy-3-methylglutaryl-CoA Reductase (HMGCR) Immune-Mediated Necrotizing Myopathy
• Intervention / Treatment: Biological: Intravenously administered pooled human immunoglobulin (IVIG)

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: James Andrews, MD; Phone Number: (205) 934-1564; Email: jaandrews@uabmc.edu
• Study Contact Backup: Name: Hannah E Howell, MS; Phone Number: 205-996-6552; Email: heburns@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
      • Principal Investigator: James Andrews, MD
      • Contact: James Andrews, MD; Phone Number: (205) 934-1564; Email: jaandrews@uabmc.edu
      • Contact: Hannah E Howell, MS; Phone Number: 205-996-6552; Email: heburns@uabmc.edu
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Not yet recruiting
      • Johns Hopkins University
      • Contact: Grazyna Purwin; Email: gpurwin1@jhmi.edu
      • Contact: Lisa Christopher-Stine, MD, MPH; Phone Number: 410-550-6962; Email: lchrist4@jhmi.edu
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • Not yet recruiting
      • University of Pittsburgh
      • Contact: Rohit Aggarwal, MD, MS; Phone Number: 412-624-4141; Email: aggarwalr@upmc.edu
      • Contact: Diane C Koontz; Email: dik4@pitt.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • University of Texas Health Science Center at Houston
  • Washington
    • Seattle, Washington, United States, 98195
      • Active, not recruiting
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenously Administered Pooled Human Immunoglobulin (IVIG); Participants will receive intravenously administered pooled human immunoglobulin (IVIG) 2g/kg every 4 weeks for 24 weeks.	Biological: Intravenously administered pooled human immunoglobulin (IVIG); IVIG 2g/kg every 4 weeks for 12 weeks (3 doses); Other Names: Octagram -Immune Globulin Intravenous (Human)
No Intervention: Placebo; Participants will receive an infusion of 0.9% sodium chloride solution every 4 weeks for 16 weeks at equivalent volume to corresponding IVIG weight-based dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in serum creatine kinase (CK)	Primary Efficacy Outcome	Week 0 to 12

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Octapharma USA, Inc.; CSI Pharmacy
• Investigators: Principal Investigator: James Andrews, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: September 12, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Diseases; Muscular Diseases; Immunologic Factors; Physiological Effects of Drugs; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 300013467; 1R21AR083566-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No