Intravenous Immunoglobulin for Muscular Dystrophy

Overseen By James Andrews, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Statins, Rituximab, Biologics, others

Disqualifiers: Anaphylaxis to IVIG, Cardiovascular events, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

12 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications, but you cannot use more than one oral DMARD, change your DMARD dose within 4 weeks before screening, or use certain medications like rituximab, plasma exchange, or statins before joining. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Intravenous Immunoglobulin (IVIG) for Muscular Dystrophy?

IVIG has been shown to be effective in treating several neuromuscular disorders like Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, which suggests it might help with muscular dystrophy as well. However, there is limited direct evidence for its use in muscular dystrophy specifically. ^{1 2 3 4 5}

Is intravenous immunoglobulin (IVIG) safe for use in humans?

Intravenous immunoglobulin (IVIG) is generally well tolerated and has a good safety profile, though some adverse events can occur. In a study of rapid infusion in patients with neuromuscular disorders, 26% experienced adverse events, most of which were minor, and all patients recovered without long-term effects. The incidence of adverse reactions in various studies ranges from 1% to 81%, but it is still considered a safe therapy. ^{3 6 7 8 9}

How is the drug IVIG different from other treatments for muscular dystrophy?

IVIG (intravenous immunoglobulin) is unique because it is made from the plasma of many blood donors and is administered directly into the bloodstream. It is used to treat a variety of autoimmune and inflammatory conditions, and its use in muscular dystrophy is novel as it may help by modulating the immune system, unlike traditional treatments that focus on muscle strengthening or gene therapy. ^{3 10 11 12 13}

What is the purpose of this trial?

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.

Research Team

James Andrews, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for individuals with active anti-HMGCR immune-mediated necrotizing myopathy (IMNM), a muscle disease. Participants must meet specific health criteria to join and be willing to potentially receive a placebo. Those who have conditions that might interfere with the study or its results are not eligible.

Inclusion Criteria

I am 16 years old or older.

My muscle disease started less than 3 years ago.

I have tested positive for anti-HMGCR antibodies.

Exclusion Criteria

I am currently taking statin medication.

I am not pregnant, breastfeeding, and am willing to use effective birth control during the study.

Wells' Criteria for Deep Vein Thrombosis score of 2 or more at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either IVIG or placebo at weeks 0, 4, and 8

12 weeks

3 visits (in-person)

Open-label extension

Participants receive IVIG at weeks 12, 16, and 20

12 weeks

3 visits (in-person)

Follow-up

Participants return at week 24 for a final non-infusion visit to reassess safety, tolerability, and efficacy outcome

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Intravenously administered pooled human immunoglobulin (IVIG)

Trial Overview The MIGHT Trial is testing the effects of IVIG, an intravenous treatment made from pooled human immunoglobulin, on IMNM. Half of the participants will receive IVIG and half will get a saline solution as placebo, randomly assigned. The main outcomes will be measured at week 12.

Participant Groups

Group I: Intravenously Administered Pooled Human Immunoglobulin (IVIG) Experimental Treatment 1 Intervention

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

Group II: Placebo Active Control 1 Intervention

Participants will receive an infusion of 0.9% sodium chloride solution every 4 weeks for 24 weeks at equivalent volume to corresponding IVIG weight-based dose.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

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

Collaborator

Trials

508

Recruited

1,090,000+

Findings from Research

Intravenous immunoglobulin (IVIG) preparations, developed to be well tolerated and safe for administration, have transformed the treatment of immunodeficiency syndromes and are effective in preventing infections in patients with compromised immune systems.

IVIG is also beneficial in treating certain autoimmune diseases, potentially due to its ability to inhibit harmful immune responses and protect cells from damage, showcasing its versatility beyond just infection prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Historic aspects of intravenous immunoglobulin therapy. Good, RA., Lorenz, E.[2019]

A study of 345 pediatric patients receiving intravenous immunoglobulin (IVIG) at Hamad General Hospital found that IVIG has a good safety profile, with low incidence of severe adverse drug reactions (ADRs) such as fever (5.8%) and chills (2.6%).

The only significant factor associated with the occurrence of ADRs was the specific brand of IVIG used, indicating that different formulations may have varying safety profiles, and further research is needed to explore this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of intravenous immunoglobulin in pediatric patients: a retrospective, 1-year observational study. Elajez, R., Ezzeldin, A., Gaber, H.[2022]

In a study of 305 intravenous immunoglobulin G (IVIG) infusions given to 111 pediatric patients, only 3.9% of infusions resulted in adverse reactions, indicating a low incidence of side effects in this population.

The most severe adverse reactions included two cases of aseptic meningitis and one case of seizures, all of which resolved completely, suggesting that while IVIG is generally safe, monitoring for rare severe reactions is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital. Yori, S., Belleri, F., Testard, J., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Historic aspects of intravenous immunoglobulin therapy. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin: striving for appropriate use. [2006]

3. United States pubmed.ncbi.nlm.nih.gov

Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Consensus statement: the use of intravenous immunoglobulin in the treatment of neuromuscular conditions report of the AANEM ad hoc committee. [2009]

5. United States pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin therapy in rheumatic diseases. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Identification and comparison of adverse events for preparations of IVIG in patients with neuromuscular diseases. [2010]

7. United States pubmed.ncbi.nlm.nih.gov

Rapid infusion of intravenous immune globulin in patients with neuromuscular disorders. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of intravenous immunoglobulin in pediatric patients: a retrospective, 1-year observational study. [2022]

9. Argentina pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin in paediatric neurology: safety, adherence to guidelines, and long-term outcome. [2019]

11. Canada pubmed.ncbi.nlm.nih.gov

Successful treatment of severe muscle necrosis with intravenous immunoglobulin. [2004]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Elevated creatinine in a patient on IVIG-therapy. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. [2021]