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

NCT ID: NCT06599697

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-27
• Study Completion Date: 2027-06-30

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 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.

Conditions

Anti-3-hydroxy-3-methylglutaryl-CoA Reductase (HMGCR) Immune-Mediated Necrotizing Myopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Intravenously Administered Pooled Human Immunoglobulin (IVIG)

Participants will receive intravenously administered pooled human immunoglobulin (IVIG) 2g/kg every 4 weeks for 24 weeks.

Group Type: EXPERIMENTAL

Intravenously administered pooled human immunoglobulin (IVIG)

Intervention Type: BIOLOGICAL

IVIG 2g/kg every 4 weeks for 12 weeks (3 doses)

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Intravenously administered pooled human immunoglobulin (IVIG)

IVIG 2g/kg every 4 weeks for 12 weeks (3 doses)

Intervention Type: BIOLOGICAL

Other Intervention Names

Octagram -Immune Globulin Intravenous (Human)

Eligibility Criteria

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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Octapharma USA, Inc.

UNKNOWN

Sponsor Role: collaborator

CSI Pharmacy

UNKNOWN

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

James Andrews

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James Andrews, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status: RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

Site Status: NOT_YET_RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status: NOT_YET_RECRUITING

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status: ACTIVE_NOT_RECRUITING

University of Washington

Seattle, Washington, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

James Andrews, MD

Role: CONTACT

jaandrews@uabmc.edu

(205) 934-1564

Hannah E Howell, MS

Role: CONTACT

heburns@uabmc.edu

205-996-6552

Facility Contacts

James Andrews, MD

Role: primary

jaandrews@uabmc.edu

(205) 934-1564

Hannah E Howell, MS

Role: backup

heburns@uabmc.edu

205-996-6552

Lisa Christopher-Stine, MD, MPH

Role: primary

lchrist4@jhmi.edu

410-550-6962

Grazyna Purwin

Role: backup

gpurwin1@jhmi.edu

Rohit Aggarwal, MD, MS

Role: primary

aggarwalr@upmc.edu

412-624-4141

Diane C Koontz

Role: backup

dik4@pitt.edu

Other Identifiers

1R21AR083566-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

300013467

Identifier Type: -

Identifier Source: org_study_id