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

NCT06599697 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 3000134671R21AR083566-01A1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• Percentage change in serum creatine kinase (CK)

  Primary Efficacy Outcome

  Week 0 to 12

Study Arms (2)

Intravenously Administered Pooled Human Immunoglobulin (IVIG)

EXPERIMENTAL

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

Biological: Intravenously administered pooled human immunoglobulin (IVIG)

Placebo

NO INTERVENTION

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.

Interventions

Intravenously administered pooled human immunoglobulin (IVIG) BIOLOGICAL

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

Also known as: Octagram -Immune Globulin Intravenous (Human)

Intravenously Administered Pooled Human Immunoglobulin (IVIG)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Octapharma USA, Inc.: collaborator
• University of Alabama at Birmingham: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• CSI Pharmacy: collaborator

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21218, United States

NOT YET RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

NOT YET RECRUITING

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

University of Washington

Seattle, Washington, 98195, United States

ACTIVE NOT RECRUITING

Study Officials

• James Andrews, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Andrews, MD

CONTACT

(205) 934-1564; jaandrews@uabmc.edu

Hannah E Howell, MS

CONTACT

205-996-6552; heburns@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Using an online randomization tool (e.g. REDCap), 12 total participants will be randomized 1:1 in blocks of 4 to receive either intravenously administered pooled human immunoglobulin (IVIG) 2g/kg every 4 weeks or placebo (0.9% sodium chloride solution at equivalent volume to corresponding IVIG weight-based dose). The home infusion research pharmacy (CSI Pharmacy) will assign treatment status using the randomization tool and will prepare IVIG or placebo for home infusion nursing staff in a blinded fashion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: 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 will be offered an open-label extension to receive IVIG at weeks 12, 16, and 20.

Study Record Dates

• First Submitted: September 12, 2024
• First Posted: September 19, 2024
• Study Start: October 27, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: February 24, 2026

Record last verified: 2026-02

Locations

US (5)